Advertisement
Translational Research
Advanced searchSave search
Review Article| Volume 234, P1-19, August 2021

Novel treatments for chronic pain: moving beyond opioids

  • Joseph B O'Brien
    Affiliations
    Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa
    Search for articles by this author
  • David L Roman
    Correspondence
    Reprint requests: David L Roman, Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, 180 S Grand Ave, CPB 538, Iowa City, IA 52245.
    Affiliations
    Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa

    Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
    Search for articles by this author
Published:March 13, 2021DOI:https://doi.org/10.1016/j.trsl.2021.03.008
Novel treatments for chronic pain: moving beyond opioids
Previous ArticleAuthor Guidelines
Next ArticleTargeting T-type/CaV3.2 channels for chronic pain
      It is essential that safe and effective treatment options be available to patients suffering from chronic pain. The emergence of an opioid epidemic has shaped public opinions and created stigmas surrounding the use of opioids for the management of pain. This reality, coupled with high risk of adverse effects from chronic opioid use, has led chronic pain patients and their healthcare providers to utilize nonopioid treatment approaches. In this review, we will explore a number of cellular reorganizations that are associated with the development and progression of chronic pain. We will also discuss the safety and efficacy of opioid and nonopioid treatment options for chronic pain. Finally, we will review the evidence for adenylyl cyclase type 1 (AC1) as a novel target for the treatment of chronic pain.

      Abbreviations:

      5-HT (Serotonin), AA (Arachidonic acid), AC (Adenylyl Cyclase), ACC (Anterior cingulate cortex), AMP (Adenosine monophosphate), ATP (Adenosine triphosphate), CaM (Calmodulin), cAMP (Cyclic adenosine monophosphate), CB (Cannabinoid), CDZ (Calmidazolium), CNS (Central nervous system), COX (Cyclooxygenase), CRE (cAMP response element), CREB (CRE- binding protein), CV (Cardiovascular), DA (Dopamine), DKO (Double knockout), DOR (Delta (δ) opioid receptor), FSK (Forskolin), GABA (Gamma aminobutyric acid), GI (Gastrointestinal), GPCR (G protein coupled receptors), HEK (Human embryonic kidney), IC (Insular cortex), KO (Knockout), KOR (Kappa (κ) opioid receptor), L-LTP (Late phase long term potentiation), LTP (Long term potentiation), MOR (Mu (μ) opioid receptor), NA (Nucleus Accumbens), NE (Norepinephrine), NOR (Nociceptin opioid receptor), NSAID (nonsteroidal anti-inflammatory), PG (Prostaglandin), PGE2 (Prostaglandin E2), PKA (Protein kinase A), PNS (Peripheral nervous system), PPI (Protein-protein interaction), TCA (Tricyclic anti-depressant), TNFα (Tumor necrosis factor alpha)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Translational Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Cogan J
        • Ouimette MF
        • Vargas-Schaffer G
        • Yegin Z
        • Deschamps A
        • Denault A.
        Patient attitudes and beliefs regarding pain medication after cardiac surgery: barriers to adequate pain management.
        Pain Manag Nurs. 2014; 15 (Epub 2013/03/15PubMed PMID: 23485659): 574-579https://doi.org/10.1016/j.pmn.2013.01.003
        View in Article
        • Reddy A
        • Yennurajalingam S
        • Bruera E.
        Whatever my mother wants”: barriers to adequate pain management.
        J Palliat Med. 2013; 16 (Epub 2012/09/06PubMed PMID: 22946542; PubMed Central PMCID: PMCPMC3667420): 709-712https://doi.org/10.1089/jpm.2012.0189
        View in Article
        • Hurstak EE
        • Kushel M
        • Chang J
        • Ceasar R
        • Zamora K
        • Miaskowski C
        • et al.
        The risks of opioid treatment: perspectives of primary care practitioners and patients from safety-net clinics.
        Subst Abus. 2017; 38 (Epub 2017/04/11PubMed PMID: 28394752; PubMed Central PMCID: PMCPMC5568522): 213-221https://doi.org/10.1080/08897077.2017.1296524
        View in Article
        • Kahan M
        • Srivastava A
        • Wilson L
        • Gourlay D
        • Midmer D.
        Misuse of and dependence on opioids: study of chronic pain patients.
        Can Fam Physician. 2006; 52 (Epub 2007/02/07. PubMed PMID: 17279218; PubMed Central PMCID: PMCPMC1783735): 1081-1087
        View in Article
        • Volkow N
        • Benveniste H
        • McLellan AT.
        Use and misuse of opioids in chronic pain.
        Annu Rev Med. 2018; 69 (Epub 2017/10/17PubMed PMID: 29029586): 451-465https://doi.org/10.1146/annurev-med-011817-044739
        View in Article
        • Sehgal N
        • Colson J
        • Smith HS.
        Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.
        Expert Rev Neurother. 2013; 13 (Epub 2013/11/02PubMed PMID: 24175722): 1201-1220https://doi.org/10.1586/14737175.2013.846517
        View in Article
        • Garland EL
        • Froeliger B
        • Zeidan F
        • Partin K
        • Howard MO.
        The downward spiral of chronic pain, prescription opioid misuse, and addiction: cognitive, affective, and neuropsychopharmacologic pathways.
        Neurosci Biobehav Rev. 2013; 37 (Epub 2013/08/31PubMed PMID: 23988582; PubMed Central PMCID: PMCPMC3967721): 2597-2607https://doi.org/10.1016/j.neubiorev.2013.08.006
        View in Article
        • Kosten TR
        • George TP.
        The neurobiology of opioid dependence: implications for treatment.
        Sci Pract Perspect. 2002; 1 (Epub 2008/06/24PubMed PMID: 18567959; PubMed Central PMCID: PMCPMC2851054): 13-20https://doi.org/10.1151/spp021113
        View in Article
        • Gendron L
        • Cahill CM
        • von Zastrow M
        • Schiller PW
        • Pineyro G.
        Molecular pharmacology of delta-opioid receptors.
        Pharmacol Rev. 2016; 68 (Epub 2016/06/28PubMed PMID: 27343248; PubMed Central PMCID: PMCPMC4931872): 631-700https://doi.org/10.1124/pr.114.008979
        View in Article
        • Williams JT
        • Ingram SL
        • Henderson G
        • et al.
        Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.
        Pharmacol Rev. 2013; 65 (Epub 2013/01/17PubMed PMID: 23321159; PubMed Central PMCID: PMCPMC3565916): 223-254https://doi.org/10.1124/pr.112.005942
        View in Article
        • Ueda H
        • Ueda M.
        Mechanisms underlying morphine analgesic tolerance and dependence.
        Front Biosci (Landmark Ed). 2009; 14 (Epub 2009/06/02.PubMed PMID: 19482614): 5260-5272https://doi.org/10.2741/3596
        View in Article
        • Baldini A
        • Von Korff M
        • Lin EH.
        A review of potential adverse effects of long-term opioid therapy: a practitioner's guide.
        Prim Care Companion CNS Disord. 2012; 14 (Epub 2012/10/30PubMed PMID: 23106029; PubMed Central PMCID: PMCPMC3466038)https://doi.org/10.4088/PCC.11m01326
        View in Article
        • Crofford LJ.
        Adverse effects of chronic opioid therapy for chronic musculoskeletal pain.
        Nat Rev Rheumatol. 2010; 6 (Epub 2010/04/02PubMed PMID: 20357788): 191-197https://doi.org/10.1038/nrrheum.2010.24
        View in Article
        • Gudin J
        • Kaufman AG
        • Datta S.
        Are opioids needed to treat chronic low back pain? A review of treatment options and analgesics in development.
        J Pain Res. 2020; 13 (Epub 2020/06/12PubMed PMID: 32523371; PubMed Central PMCID: PMCPMC7234959): 1007-1022https://doi.org/10.2147/JPR.S226483
        View in Article

      15. Peck J, Urits I, Peoples S, Foster L, Malla A, Berger AA, et al. A comprehensive review of over the counter treatment for chronic low back pain. Pain Ther. 2020. Epub 2020/11/06. 10.1007/s40122-020-00209-w. PubMed PMID: 33150555.

        View in Article
        • Labianca R
        • Sarzi-Puttini P
        • Zuccaro SM
        • Cherubino P
        • Vellucci R
        • Fornasari D.
        Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain.
        Clin Drug Investig. 2012; 32 (Epub 2012/03/06PubMed PMID: 22356224): 53-63https://doi.org/10.2165/11630080-000000000-00000
        View in Article
        • Schug SA
        • Garrett WR
        • Gillespie G.
        Opioid and non-opioid analgesics.
        Best Pract Res Clin Anaesthesiol. 2003; 17 (Epub 2003/05/20PubMed PMID: 12751551): 91-110https://doi.org/10.1053/bean.2003.0267
        View in Article
        • Sarzi-Puttini P
        • Vellucci R
        • Zuccaro SM
        • Cherubino P
        • Labianca R
        • Fornasari D.
        The appropriate treatment of chronic pain.
        Clin Drug Investig. 2012; 32 (Epub 2013/02/15PubMed PMID: 23389873): 21-33https://doi.org/10.2165/11630050-000000000-00000
        View in Article
        • Gaskin DJ
        • Richard P.
        The economic costs of pain in the United States.
        J Pain. 2012; 13 (Epub 2012/05/23PubMed PMID: 22607834): 715-724https://doi.org/10.1016/j.jpain.2012.03.009
        View in Article
        • Christie MJ.
        Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction.
        Br J Pharmacol. 2008; 154 (Epub 2008/04/17PubMed PMID: 18414400; PubMed Central PMCID: PMCPMC2442443): 384-396https://doi.org/10.1038/bjp.2008.100
        View in Article
        • Dacher M
        • Nugent FS.
        Opiates and plasticity.
        Neuropharmacology. 2011; 61 (Epub 2011/01/29PubMed PMID: 21272593): 1088-1096https://doi.org/10.1016/j.neuropharm.2011.01.028
        View in Article
        • Langlois LD
        • Nugent FS.
        Opiates and plasticity in the ventral tegmental area.
        ACS Chem Neurosci. 2017; 8 (Epub 2017/08/05PubMed PMID: 28768409; PubMed Central PMCID: PMCPMC5775906): 1830-1838https://doi.org/10.1021/acschemneuro.7b00281
        View in Article
        • Mazei-Robison MS
        • Nestler EJ.
        Opiate-induced molecular and cellular plasticity of ventral tegmental area and locus coeruleus catecholamine neurons.
        Cold Spring Harb Perspect Med. 2012; 2 (Epub 2012/07/05PubMed PMID: 22762025; PubMed Central PMCID: PMCPMC3385942)a012070https://doi.org/10.1101/cshperspect.a012070
        View in Article
        • Li XH
        • Chen QY
        • Zhuo M.
        Neuronal adenylyl cyclase targeting central plasticity for the treatment of chronic pain.
        Neurotherapeutics. 2020; 17 (Epub 2020/09/17PubMed PMID: 32935298; PubMed Central PMCID: PMCPMC7609634): 861-873https://doi.org/10.1007/s13311-020-00927-1
        View in Article
        • Zhuo M.
        Targeting neuronal adenylyl cyclase for the treatment of chronic pain.
        Drug Discov Today. 2012; 17 (Epub 2012/03/13PubMed PMID: 22405897): 573-582https://doi.org/10.1016/j.drudis.2012.01.009
        View in Article
        • Zhuo M.
        • Cortical LTP
        A synaptic model for chronic pain.
        Adv Exp Med Biol. 2018; 1099 (Epub 2018/10/12PubMed PMID: 30306522): 147-155https://doi.org/10.1007/978-981-13-1756-9_13
        View in Article
        • Li XH
        • Miao HH
        • Zhuo M.
        NMDA receptor dependent long-term potentiation in chronic pain.
        Neurochem Res. 2019; 44 (Epub 2018/08/16PubMed PMID: 30109556; PubMed Central PMCID: PMCPMC6420414): 531-538https://doi.org/10.1007/s11064-018-2614-8
        View in Article
        • Elman I
        • Borsook D.
        Common brain mechanisms of chronic pain and addiction.
        Neuron. 2016; 89 (Epub 2016/01/10PubMed PMID: 26748087): 11-36https://doi.org/10.1016/j.neuron.2015.11.027
        View in Article
        • Chapman CR
        • Vierck CJ.
        The transition of acute postoperative pain to chronic pain: an integrative overview of research on mechanisms.
        J Pain. 2017; 18 (e1- e38. Epub 2016/12/03PubMed PMID: 27908839): 359https://doi.org/10.1016/j.jpain.2016.11.004
        View in Article
        • Katz J
        • Seltzer Z.
        Transition from acute to chronic postsurgical pain: risk factors and protective factors.
        Expert Rev Neurother. 2009; 9 (Epub 2009/05/01PubMed PMID: 19402781): 723-744https://doi.org/10.1586/ern.09.20
        View in Article
        • Heinricher MM.
        Pain modulation and the transition from acute to chronic pain.
        Adv Exp Med Biol. 2016; 904 (Epub 2016/02/24PubMed PMID: 26900066): 105-115https://doi.org/10.1007/978-94-017-7537-3_8
        View in Article
        • Dessauer CW
        • Watts VJ
        • Ostrom RS
        • Conti M
        • Dove S
        • Seifert R.
        International Union of Basic and Clinical Pharmacology. CI. structures and small molecule modulators of mammalian adenylyl cyclases.
        Pharmacol Rev. 2017; 69 (Epub 2017/03/04PubMed PMID: 28255005; PubMed Central PMCID: PMCPMC5394921): 93-139https://doi.org/10.1124/pr.116.013078
        View in Article
        • Sadana R
        • Dessauer CW.
        Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies.
        Neurosignals. 2009; 17 (Epub 2008/10/25PubMed PMID: 18948702; PubMed Central PMCID: PMCPMC2790773): 5-22https://doi.org/10.1159/000166277
        View in Article
        • Vadakkan KI
        • Wang H
        • Ko SW
        • et al.
        Genetic reduction of chronic muscle pain in mice lacking calcium/calmodulin-stimulated adenylyl cyclases.
        Mol Pain. 2006; 2 (Epub 2006/03/01PubMed PMID: 16503978; PubMed Central PMCID: PMCPMC1395303): 7https://doi.org/10.1186/1744-8069-2-7
        View in Article
        • Corder G
        • Doolen S
        • Donahue RR
        • et al.
        Constitutive mu-opioid receptor activity leads to long-term endogenous analgesia and dependence.
        Science. 2013; 341 (Epub 2013/09/21PubMed PMID: 24052307; PubMed Central PMCID: PMCPMC4440417): 1394-1399https://doi.org/10.1126/science.1239403
        View in Article
        • Wang H
        • Xu H
        • Wu LJ
        • et al.
        Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain.
        Sci Transl Med. 2011; 3 (ra3. Epub 2011/01/14PubMed PMID: 21228397): 65https://doi.org/10.1126/scitranslmed.3001269
        View in Article
        • Wei F
        • Qiu CS
        • Kim SJ
        • et al.
        Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases.
        Neuron. 2002; 36 (Epub 2002/11/21PubMed PMID: 12441059): 713-726https://doi.org/10.1016/s0896-6273(02)01019-x
        View in Article
        • Treede RD
        • Rief W
        • Barke A
        • et al.
        A classification of chronic pain for ICD-11.
        Pain. 2015; 156 (Epub 2015/04/07PubMed PMID: 25844555; PubMed Central PMCID: PMCPMC4450869): 1003-1007https://doi.org/10.1097/j.pain.0000000000000160
        View in Article
        • Wijma AJ
        • van Wilgen CP
        • Meeus M
        • Nijs J.
        Clinical biopsychosocial physiotherapy assessment of patients with chronic pain: The first step in pain neuroscience education.
        Physiother Theory Pract. 2016; 32 (Epub 2016/06/29PubMed PMID: 27351769): 368-384https://doi.org/10.1080/09593985.2016.1194651
        View in Article
        • Lumley MA
        • Cohen JL
        • Borszcz GS
        • et al.
        Pain and emotion: a biopsychosocial review of recent research.
        J Clin Psychol. 2011; 67 (Epub 2011/06/08PubMed PMID: 21647882; PubMed Central PMCID: PMCPMC3152687): 942-968https://doi.org/10.1002/jclp.20816
        View in Article
        • Mills SEE
        • Nicolson KP
        • Smith BH.
        Chronic pain: a review of its epidemiology and associated factors in population-based studies.
        Br J Anaesth. 2019; 123 (Epub 2019/05/14PubMed PMID: 31079836; PubMed Central PMCID: PMCPMC6676152): e273-ee83https://doi.org/10.1016/j.bja.2019.03.023
        View in Article
        • van Hecke O
        • Torrance N
        • Smith BH.
        Chronic pain epidemiology and its clinical relevance.
        Br J Anaesth. 2013; 111 (Epub 2013/06/26.PubMed PMID: 23794640): 13-18https://doi.org/10.1093/bja/aet123
        View in Article
        • National Institute of Neurological Disorders NIoH
        Pain: hope through research.
        J Pain Palliat Care Pharmacother. 2009; 23 (Epub 2009/08/12PubMed PMID: 19670028): 307-322https://doi.org/10.1080/15360280903099141
        View in Article
        • Fornasari D.
        Pain mechanisms in patients with chronic pain.
        Clin Drug Investig. 2012; 32 (Epub 2012/03/06PubMed PMID: 22356223): 45-52https://doi.org/10.2165/11630070-000000000-00000
        View in Article
        • Kuner R
        • Flor H.
        Structural plasticity and reorganisation in chronic pain.
        Nat Rev Neurosci. 2017; 18 (Epub 2017/07/14PubMed PMID: 28704354): 113https://doi.org/10.1038/nrn.2017.5
        View in Article
        • Yang S
        • Chang MC.
        Chronic pain: structural and functional changes in brain structures and associated negative affective states.
        Int J Mol Sci. 2019; 20 (Epub 2019/06/30PubMed PMID: 31248061; PubMed Central PMCID: PMCPMC6650904)https://doi.org/10.3390/ijms20133130
        View in Article
        • Dubin AE
        • Patapoutian A.
        Nociceptors: the sensors of the pain pathway.
        J Clin Invest. 2010; 120 (Epub 2010/11/03PubMed PMID: 21041958; PubMed Central PMCID: PMCPMC2964977): 3760-3772https://doi.org/10.1172/JCI42843
        View in Article
        • Basbaum AI
        • Bautista DM
        • Scherrer G
        • Julius D
        Cellular and molecular mechanisms of pain.
        Cell. 2009; 139 (Epub 2009/10/20PubMed PMID: 19837031; PubMed Central PMCID: PMCPMC2852643): 267-284https://doi.org/10.1016/j.cell.2009.09.028
        View in Article
        • Pinho-Ribeiro FA
        • Verri Jr., WA
        • Chiu IM
        Nociceptor sensory neuron-immune interactions in pain and inflammation.
        Trends Immunol. 2017; 38 (Epub 2016/10/30PubMed PMID: 27793571; PubMed Central PMCID: PMCPMC5205568): 5-19https://doi.org/10.1016/j.it.2016.10.001
        View in Article
        • Berlucchi G
        • Buchtel HA.
        Neuronal plasticity: historical roots and evolution of meaning.
        Exp Brain Res. 2009; 192 (Epub 2008/11/13PubMed PMID: 19002678): 307-319https://doi.org/10.1007/s00221-008-1611-6
        View in Article
        • Mansour AR
        • Farmer MA
        • Baliki MN
        • Apkarian AV.
        Chronic pain: the role of learning and brain plasticity.
        Restor Neurol Neurosci. 2014; 32 (Epub 2013/04/23PubMed PMID: 23603439; PubMed Central PMCID: PMCPMC4922795): 129-139https://doi.org/10.3233/RNN-139003
        View in Article
        • McCarberg B
        • Peppin J.
        Pain pathways and nervous system plasticity: learning and memory in pain.
        Pain Med. 2019; 20 (Epub 2019/03/14.PubMed PMID: 30865778): 2421-2437https://doi.org/10.1093/pm/pnz017
        View in Article
        • Prescott SA
        • Ma Q
        • De Koninck Y.
        Normal and abnormal coding of somatosensory stimuli causing pain.
        Nat Neurosci. 2014; 17 (Epub 2014/01/30PubMed PMID: 24473266; PubMed Central PMCID: PMCPMC4079041): 183-191https://doi.org/10.1038/nn.3629
        View in Article
        • Latremoliere A
        • Woolf CJ.
        Central sensitization: a generator of pain hypersensitivity by central neural plasticity.
        J Pain. 2009; 10 (Epub 2009/08/29PubMed PMID: 19712899; PubMed Central PMCID: PMCPMC2750819): 895-926https://doi.org/10.1016/j.jpain.2009.06.012
        View in Article
        • Reichling DB
        • Levine JD.
        Critical role of nociceptor plasticity in chronic pain.
        Trends Neurosci. 2009; 32 (Epub 2009/09/29PubMed PMID: 19781793; PubMed Central PMCID: PMCPMC2787756): 611-618https://doi.org/10.1016/j.tins.2009.07.007
        View in Article
        • McGreevy K
        • Bottros MM
        • Raja SN.
        Preventing chronic pain following acute pain: risk factors, preventive strategies, and their efficacy.
        Eur J Pain Suppl. 2011; 5 (Epub 2011/11/22PubMed PMID: 22102847; PubMed Central PMCID: PMCPMC3217302): 365-372https://doi.org/10.1016/j.eujps.2011.08.013
        View in Article
        • Li JX
        • Zhang Y.
        Emerging drug targets for pain treatment.
        EurJ Pharmacol. 2012; 681 (Epub 2012/02/09PubMed PMID: 22314220): 1-5https://doi.org/10.1016/j.ejphar.2012.01.017
        View in Article
        • Turnaturi R
        • Chiechio S
        • Salerno L
        • et al.
        Progress in the development of more effective and safer analgesics for pain management.
        Eur J Med Chem. 2019; 183 (Epub 2019/09/25PubMed PMID: 31550662)111701https://doi.org/10.1016/j.ejmech.2019.111701
        View in Article
        • Watts VJ.
        Selective adenylyl cyclase type 1 inhibitors as potential opioid alternatives for chronic pain.
        Neuropsychopharmacology. 2018; 43 (Epub 2017/12/02PubMed PMID: 29192658; PubMed Central PMCID: PMCPMC5719099): 215-216https://doi.org/10.1038/npp.2017.190
        View in Article
        • Ghlichloo I
        • Gerriets V.
        Nonsteroidal Anti-inflammatory Drugs (NSAIDs). StatPearls.
        Treasure Island (FL), 2020
        View in Article
        • Scarpignato C
        • Lanas A
        • Blandizzi C
        • et al.
        Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis–an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks.
        BMC Med. 2015; 13 (Epub 2015/04/11PubMed PMID: 25857826; PubMed Central PMCID: PMCPMC4365808): 55https://doi.org/10.1186/s12916-015-0285-8
        View in Article
        • Pearce JM.
        Chronic regional pain and chronic pain syndromes.
        Spinal Cord. 2005; 43 (Epub 2005/01/06PubMed PMID: 15632949): 263-268https://doi.org/10.1038/sj.sc.3101709
        View in Article
        • Ho KY
        • Gwee KA
        • Cheng YK
        • Yoon KH
        • Hee HT
        • Omar AR.
        Nonsteroidal anti-inflammatory drugs in chronic pain: implications of new data for clinical practice.
        J Pain Res. 2018; 11 (Epub 2018/10/06PubMed PMID: 30288088; PubMed Central PMCID: PMCPMC6160277): 1937-1948https://doi.org/10.2147/JPR.S168188
        View in Article
        • Minghetti L.
        Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases.
        J Neuropathol Exp Neurol. 2004; 63 (Epub 2004/09/30PubMed PMID: 15453089): 901-910https://doi.org/10.1093/jnen/63.9.901
        View in Article
        • Osthues T
        • Sisignano M.
        Oxidized lipids in persistent pain states.
        Front Pharmacol. 2019; 10 (Epub 2019/11/05PubMed PMID: 31680947; PubMed Central PMCID: PMCPMC6803483): 1147https://doi.org/10.3389/fphar.2019.01147
        View in Article
        • Davies P
        • Bailey PJ
        • Goldenberg MM
        • Ford-Hutchinson AW.
        The role of arachidonic acid oxygenation products in pain and inflammation.
        Annu Rev Immunol. 1984; 2 (Epub 1984/01/01PubMed PMID: 6100476): 335-357https://doi.org/10.1146/annurev.iy.02.040184.002003
        View in Article
        • Sostres C
        • Gargallo CJ
        • Arroyo MT
        • Lanas A.
        Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract.
        Best Pract Res Clin Gastroenterol. 2010; 24 (Epub 2010/03/17PubMed PMID: 20227026): 121-132https://doi.org/10.1016/j.bpg.2009.11.005
        View in Article
        • Ballinger A
        • Smith G.
        COX-2 inhibitors vs. NSAIDs in gastrointestinal damage and prevention.
        Expert Opin Pharmacother. 2001; 2 (Epub 2001/05/05PubMed PMID: 11336566): 31-40https://doi.org/10.1517/14656566.2.1.31
        View in Article
        • Robinson DR.
        Regulation of prostaglandin synthesis by antiinflammatory drugs.
        J Rheumatol Suppl. 1997; 47 (Epub 1997/02/01. PubMed PMID: 9035018): 32-39
        View in Article
        • Takeuchi K.
        Prostaglandin EP receptors and their roles in mucosal protection and ulcer healing in the gastrointestinal tract.
        Adv Clin Chem. 2010; 51 (Epub 2010/09/23.PubMed PMID: 20857620): 121-144https://doi.org/10.1016/s0065-2423(10)51005-9
        View in Article
        • Bjarnason I
        • Takeuchi K.
        Intestinal permeability in the pathogenesis of NSAID-induced enteropathy.
        J Gastroenterol. 2009; 44 (Epub 2009/02/20PubMed PMID: 19148789): 23-29https://doi.org/10.1007/s00535-008-2266-6
        View in Article
        • Khazaeinia T
        • Jamali F.
        A comparison of gastrointestinal permeability induced by diclofenac-phospholipid complex with diclofenac acid and its sodium salt.
        J Pharm Pharm Sci. 2003; 6 (Epub 2004/01/24. PubMed PMID: 14738716): 352-359
        View in Article
        • Russell RI.
        Non-steroidal anti-inflammatory drugs and gastrointestinal damage-problems and solutions.
        Postgrad Med J. 2001; 77 (Epub 2001/02/13PubMed PMID: 11161072; PubMed Central PMCID: PMCPMC1741894): 82-88https://doi.org/10.1136/pmj.77.904.82
        View in Article
        • Wallace JL.
        Pathogenesis of NSAID-induced gastroduodenal mucosal injury.
        Best Pract Res Clin Gastroenterol. 2001; 15 (Epub 2001/09/22PubMed PMID: 11566035): 691-703https://doi.org/10.1053/bega.2001.0229
        View in Article
        • Goldstein JL
        • Correa P
        • Zhao WW
        • et al.
        Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis.
        Am J Gastroenterol. 2001; 96 (Epub 2001/04/24PubMed PMID: 11316141): 1019-1027https://doi.org/10.1111/j.1572-0241.2001.03740.x
        View in Article
        • Wright JM.
        The double-edged sword of COX-2 selective NSAIDs.
        CMAJ. 2002; 167 (Epub 2002/11/13. PubMed PMID: 12427705; PubMed Central PMCID: PMCPMC134294): 1131-1137
        View in Article
        • Justice E
        • Carruthers DM.
        Cardiovascular risk and COX-2 inhibition in rheumatological practice.
        J Hum Hypertens. 2005; 19 (Epub 2004/09/24PubMed PMID: 15385947): 1-5https://doi.org/10.1038/sj.jhh.1001777
        View in Article
        • Funk CD
        • FitzGerald GA.
        COX-2 inhibitors and cardiovascular risk.
        J Cardiovasc Pharmacol. 2007; 50 (Epub 2007/11/22PubMed PMID: 18030055): 470-479https://doi.org/10.1097/FJC.0b013e318157f72d
        View in Article
        • Cheng Y
        • Austin SC
        • Rocca B
        • et al.
        Role of prostacyclin in the cardiovascular response to thromboxane A2.
        Science. 2002; 296 (Epub 2002/04/20PubMed PMID: 11964481): 539-541https://doi.org/10.1126/science.1068711
        View in Article
        • McAdam BF
        • Catella-Lawson F
        • Mardini IA
        • Kapoor S
        • Lawson JA
        • FitzGerald GA.
        Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2.
        Proc Natl Acad Sci U S A. 1999; 96 (Epub 1999/01/06PubMed PMID: 9874808; PubMed Central PMCID: PMCPMC15129): 272-277https://doi.org/10.1073/pnas.96.1.272
        View in Article
        • Fosbol EL
        • Folke F
        • Jacobsen S
        • et al.
        Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals.
        Circ Cardiovasc Qual Outcomes. 2010; 3 (Epub 2010/06/10PubMed PMID: 20530789): 395-405https://doi.org/10.1161/CIRCOUTCOMES.109.861104
        View in Article
        • Walter MF
        • Jacob RF
        • Day CA
        • Dahlborg R
        • Weng Y
        • Mason RP.
        Sulfone COX-2 inhibitors increase susceptibility of human LDL and plasma to oxidative modification: comparison to sulfonamide COX-2 inhibitors and NSAIDs.
        Atherosclerosis. 2004; 177 (Epub 2004/11/09PubMed PMID: 15530895): 235-243https://doi.org/10.1016/j.atherosclerosis.2004.10.001
        View in Article
        • Sibbald B.
        Rofecoxib (Vioxx) voluntarily withdrawn from market.
        CMAJ. 2004; 171 (Epub 2004/10/27PubMed PMID: 15505253; PubMed Central PMCID: PMCPMC526313): 1027-1028https://doi.org/10.1503/cmaj.1041606
        View in Article
        • Moore RA
        • Derry S
        • McQuay HJ.
        Cyclo-oxygenase-2 selective inhibitors and nonsteroidal anti-inflammatory drugs: balancing gastrointestinal and cardiovascular risk.
        BMC Musculoskelet Disord. 2007; 8 (Epub 2007/08/09PubMed PMID: 17683540; PubMed Central PMCID: PMCPMC2001315): 73https://doi.org/10.1186/1471-2474-8-73
        View in Article
        • Ansari A.
        The efficacy of newer antidepressants in the treatment of chronic pain: a review of current literature.
        Harv Rev Psychiatry. 2000; 7 (Epub 2000/02/26. PubMed PMID: 10689591): 257-277
        View in Article
        • Sheng J
        • Liu S
        • Wang Y
        • Cui R
        • Zhang X.
        The link between depression and chronic pain: neural mechanisms in the brain.
        Neural Plast. 2017; 2017 (Epub 2017/07/15PubMed PMID: 28706741; PubMed Central PMCID: PMCPMC5494581)9724371https://doi.org/10.1155/2017/9724371
        View in Article
        • Kirmayer LJ
        • Robbins JM
        • Dworkind M
        • Yaffe MJ.
        Somatization and the recognition of depression and anxiety in primary care.
        Am J Psychiatry. 1993; 150 (Epub 1993/05/01PubMed PMID: 8480818): 734-741https://doi.org/10.1176/ajp.150.5.734
        View in Article
        • Berger A
        • Dukes E
        • Mercadante S
        • Oster G.
        Use of antiepileptics and tricyclic antidepressants in cancer patients with neuropathic pain.
        Eur J Cancer Care (Engl). 2006; 15 (Epub 2006/04/29PubMed PMID: 16643261): 138-145https://doi.org/10.1111/j.1365-2354.2005.00624.x
        View in Article
        • Cayley Jr, WE
        Antidepressants for the treatment of neuropathic pain.
        Am Fam Physician. 2006; 73 (Epub 2006/06/15. PubMed PMID: 16770921): 1933-1934
        View in Article
        • Mico JA
        • Ardid D
        • Berrocoso E
        • Eschalier A.
        Antidepressants and pain.
        Trends Pharmacol Sci. 2006; 27 (Epub 2006/06/10PubMed PMID: 16762426): 348-354https://doi.org/10.1016/j.tips.2006.05.004
        View in Article
        • Verdu B
        • Decosterd I
        • Buclin T
        • Stiefel F
        • Berney A.
        Antidepressants for the treatment of chronic pain.
        Drugs. 2008; 68 (Epub 2008/12/20PubMed PMID: 19093703): 2611-2632https://doi.org/10.2165/0003495-200868180-00007
        View in Article
        • Obata H.
        Analgesic mechanisms of antidepressants for neuropathic pain.
        Int J Mol Sci. 2017; 18 (Epub 2017/11/22PubMed PMID: 29160850; PubMed Central PMCID: PMCPMC5713449)https://doi.org/10.3390/ijms18112483
        View in Article
        • Yokogawa F
        • Kiuchi Y
        • Ishikawa Y
        • et al.
        An investigation of monoamine receptors involved in antinociceptive effects of antidepressants.
        Anesth Analg. 2002; 95 (table of contents. Epub 2002/06/29PubMed PMID: 12088962): 163-168https://doi.org/10.1097/00000539-200207000-00029
        View in Article
        • Ignatowski TA
        • Sud R
        • Reynolds JL
        • Knight PR
        • Spengler RN.
        The dissipation of neuropathic pain paradoxically involves the presence of tumor necrosis factor-alpha (TNF).
        Neuropharmacology. 2005; 48 (Epub 2005/02/22PubMed PMID: 15721177): 448-460https://doi.org/10.1016/j.neuropharm.2004.11.001
        View in Article
        • Bertilsson L.
        Metabolism of antidepressant and neuroleptic drugs by cytochrome p450 s: clinical and interethnic aspects.
        Clin Pharmacol Ther. 2007; 82 (Epub 2007/09/28PubMed PMID: 17898711): 606-609https://doi.org/10.1038/sj.clpt.6100358
        View in Article
        • Perrot S
        • Maheu E
        • Javier RM
        • et al.
        Guidelines for the use of antidepressants in painful rheumatic conditions.
        Eur J Pain. 2006; 10 (Epub 2006/02/24PubMed PMID: 16490727): 185-192https://doi.org/10.1016/j.ejpain.2005.03.004
        View in Article
        • Volpi-Abadie J
        • Kaye AM
        • Kaye AD
        Serotonin syndrome.
        Ochsner J. 2013; 13 (Epub 2013/12/21. PubMed PMID: 24358002; PubMed Central PMCID: PMCPMC3865832): 533-540
        View in Article
        • Sidhu HS
        • Sadhotra A.
        Current status of the new antiepileptic drugs in chronic pain.
        Front Pharmacol. 2016; 7 (Epub 2016/09/10PubMed PMID: 27610084; PubMed Central PMCID: PMCPMC4996999): 276https://doi.org/10.3389/fphar.2016.00276
        View in Article
        • Xu MY
        • Wong AHC.
        GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia.
        Acta Pharmacol Sin. 2018; 39 (Epub 2018/03/23PubMed PMID: 29565038; PubMed Central PMCID: PMCPMC5943898): 733-753https://doi.org/10.1038/aps.2017.172
        View in Article
        • Yaari Y
        • Devor M.
        Phenytoin suppresses spontaneous ectopic discharge in rat sciatic nerve neuromas.
        Neurosci Lett. 1985; 58 (Epub 1985/07/04PubMed PMID: 4047470): 117-122https://doi.org/10.1016/0304-3940(85)90339-8
        View in Article
        • Tremont-Lukats IW
        • Megeff C
        • Backonja MM.
        Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy.
        Drugs. 2000; 60 (Epub 2000/12/29PubMed PMID: 11129121): 1029-1052https://doi.org/10.2165/00003495-200060050-00005
        View in Article
        • Blommel ML
        • Blommel AL.
        Pregabalin: an antiepileptic agent useful for neuropathic pain.
        Am J Health Syst Pharm. 2007; 64 (Epub 2007/07/10PubMed PMID: 17617497): 1475-1482https://doi.org/10.2146/ajhp060371
        View in Article
        • Tassone DM
        • Boyce E
        • Guyer J
        • Nuzum D.
        Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.
        Clin Ther. 2007; 29 (Epub 2007/03/24PubMed PMID: 17379045): 26-48https://doi.org/10.1016/j.clinthera.2007.01.013
        View in Article
        • Verma V
        • Singh N
        • Singh Jaggi A
        Pregabalin in neuropathic pain: evidences and possible mechanisms.
        Curr Neuropharmacol. 2014; 12 (Epub 2014/02/18PubMed PMID: 24533015; PubMed Central PMCID: PMCPMC3915349): 44-56https://doi.org/10.2174/1570159X1201140117162802
        View in Article
        • Taylor CP
        • Angelotti T
        • Fauman E.
        Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery.
        Epilepsy Res. 2007; 73 (Epub 2006/11/28PubMed PMID: 17126531): 137-150https://doi.org/10.1016/j.eplepsyres.2006.09.008
        View in Article
        • Taylor CP
        • Garrido R.
        Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for calcium channel alpha2-delta (alpha2-delta) type 1 protein.
        Neuroscience. 2008; 155 (Epub 2008/07/12PubMed PMID: 18616987): 510-521https://doi.org/10.1016/j.neuroscience.2008.05.053
        View in Article
        • Sharma U
        • Griesing T
        • Emir B
        • Young Jr, JP
        Time to onset of neuropathic pain reduction: a retrospective analysis of data from nine controlled trials of pregabalin for painful diabetic peripheral neuropathy and postherpetic neuralgia.
        Am J Ther. 2010; 17 (Epub 2010/04/16PubMed PMID: 20393345): 577-585https://doi.org/10.1097/MJT.0b013e3181d5e4 f3
        View in Article
        • Parsons B
        • Emir B
        • Clair A
        Temporal analysis of pain responders and common adverse events: when do these first appear following treatment with pregabalin.
        J Pain Res. 2015; 8 (Epub 2015/07/15PubMed PMID: 26170712; PubMed Central PMCID: PMCPMC4494606): 303-309https://doi.org/10.2147/JPR.S82806
        View in Article
        • Moore RA
        • Wiffen PJ
        • Derry S
        • McQuay HJ.
        Gabapentin for chronic neuropathic pain and fibromyalgia in adults.
        Cochrane Database Syst Rev. 2011; (Epub 2011/03/18PubMed PMID: 21412914; PubMed Central PMCID: PMCPMC4171034)CD007938https://doi.org/10.1002/14651858.CD007938.pub2
        View in Article
        • Moore RA
        • Wiffen PJ
        • Derry S
        • Toelle T
        • Rice AS.
        Gabapentin for chronic neuropathic pain and fibromyalgia in adults.
        Cochrane Database Syst Rev. 2014; (Epub 2014/04/29PubMed PMID: 24771480; PubMed Central PMCID: PMCPMC6464253)CD007938https://doi.org/10.1002/14651858.CD007938.pub3
        View in Article
        • Wiffen PJ
        • Derry S
        • Bell RF
        • et al.
        Gabapentin for chronic neuropathic pain in adults.
        Cochrane Database Syst Rev. 2017; 6 (Epub 2017/06/10PubMed PMID: 28597471; PubMed Central PMCID: PMCPMC6452908)CD007938https://doi.org/10.1002/14651858.CD007938.pub4
        View in Article
        • Wallace MS
        • Irving G
        • Cowles VE.
        Gabapentin extended-release tablets for the treatment of patients with postherpetic neuralgia: a randomized, double-blind, placebo-controlled, multicentre study.
        Clin Drug Investig. 2010; 30 (Epub 2010/09/08PubMed PMID: 20818838): 765-776https://doi.org/10.2165/11539520-000000000-00000
        View in Article
        • Li C.T.WJC
        Anticonvulsants in the treatment of pain.
        Springer Nature Switzerland, 2019
        View in Article
        • Nightingale S.
        The neuropathic pain market.
        Nat Rev Drug Discov. 2012; 11 (Epub 2012/02/02PubMed PMID: 22293560): 101-102https://doi.org/10.1038/nrd3624
        View in Article
        • Rosenberger DC
        • Blechschmidt V
        • Timmerman H
        • Wolff A
        • Treede RD.
        Challenges of neuropathic pain: focus on diabetic neuropathy.
        J Neural Transm (Vienna). 2020; 127 (Epub 2020/02/10PubMed PMID: 32036431; PubMed Central PMCID: PMCPMC7148276): 589-624https://doi.org/10.1007/s00702-020-02145-7
        View in Article
        • Punyawudho B
        • Cloyd JC
        • Leppik IE
        • et al.
        Characterization of the time course of carbamazepine deinduction by an enzyme turnover model.
        Clin Pharmacokinet. 2009; 48 (Epub 2009/07/02PubMed PMID: 19566114; PubMed Central PMCID: PMCPMC2945813): 313-320https://doi.org/10.2165/00003088-200948050-00003
        View in Article
        • Nozari A
        • Akeju O
        • Mirzakhani H
        • et al.
        Prolonged therapy with the anticonvulsant carbamazepine leads to increased plasma clearance of fentanyl.
        J Pharm Pharmacol. 2019; 71 (Epub 2019/02/23PubMed PMID: 30793320): 982-987https://doi.org/10.1111/jphp.13079
        View in Article
        • Maan JS
        • Duong Tv H
        • Saadabadi A
        Carbamazepine.
        StatPearls. Treasure Island (FL), 2020
        View in Article
        • Dai H
        • Tilley DM
        • Mercedes G
        • et al.
        Opiate-free pain therapy using carbamazepine-loaded microparticles provides up to 2 weeks of pain relief in a neuropathic pain model.
        Pain Pract. 2018; 18 (Epub 2018/05/04PubMed PMID: 29723917): 1024-1035https://doi.org/10.1111/papr.12705
        View in Article
        • Pathan H
        • Williams J.
        Basic opioid pharmacology: an update.
        Br J Pain. 2012; 6 (Epub 2012/02/01PubMed PMID: 26516461; PubMed Central PMCID: PMCPMC4590096): 11-16https://doi.org/10.1177/2049463712438493
        View in Article
        • Williams J
        Basic opioid pharmacology.
        Rev Pain. 2008; 1 (Epub 2008/03/01PubMed PMID: 26524987; PubMed Central PMCID: PMCPMC4589929): 2-5https://doi.org/10.1177/204946370800100202
        View in Article
        • Valentino RJ
        • Volkow ND.
        Untangling the complexity of opioid receptor function.
        Neuropsychopharmacology. 2018; 43 (Epub 2018/09/27PubMed PMID: 30250308; PubMed Central PMCID: PMCPMC6224460): 2514-2520https://doi.org/10.1038/s41386-018-0225-3
        View in Article
        • Lutz PE
        • Kieffer BL.
        Opioid receptors: distinct roles in mood disorders.
        Trends Neurosci. 2013; 36 (Epub 2012/12/12PubMed PMID: 23219016; PubMed Central PMCID: PMCPMC3594542): 195-206https://doi.org/10.1016/j.tins.2012.11.002
        View in Article
        • Mollereau C
        • Parmentier M
        • Mailleux P
        • et al.
        ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization.
        FEBS Lett. 1994; 341 (Epub 1994/03/14PubMed PMID: 8137918): 33-38https://doi.org/10.1016/0014-5793(94)80235-1
        View in Article
        • Zaveri NT.
        Nociceptin opioid receptor (nop) as a therapeutic target: progress in translation from preclinical research to clinical utility.
        J Med Chem. 2016; 59 (Epub 2016/02/16PubMed PMID: 26878436; PubMed Central PMCID: PMCPMC5001850): 7011-7028https://doi.org/10.1021/acs.jmedchem.5b01499
        View in Article
        • Corder G
        • Castro DC
        • Bruchas MR
        • Scherrer G.
        Endogenous and exogenous opioids in pain.
        Annu Rev Neurosci. 2018; 41 (Epub 2018/06/01PubMed PMID: 29852083; PubMed Central PMCID: PMCPMC6428583): 453-473https://doi.org/10.1146/annurev-neuro-080317-061522
        View in Article
        • Sprouse-Blum AS
        • Smith G
        • Sugai D
        • Parsa FD.
        Understanding endorphins and their importance in pain management.
        Hawaii Med J. 2010; 69 (Epub 2010/04/20. PubMed PMID: 20397507; PubMed Central PMCID: PMCPMC3104618): 70-71
        View in Article
        • Suvas S.
        Role of substance p neuropeptide in inflammation, wound healing, and tissue homeostasis.
        J Immunol. 2017; 199 (Epub 2017/08/23PubMed PMID: 28827386; PubMed Central PMCID: PMCPMC5657331): 1543-1552https://doi.org/10.4049/jimmunol.1601751
        View in Article
        • Spanagel R
        • Herz A
        • Bals-Kubik R
        • Shippenberg TS.
        Beta-endorphin-induced locomotor stimulation and reinforcement are associated with an increase in dopamine release in the nucleus accumbens.
        Psychopharmacology (Berl). 1991; 104 (Epub 1991/01/01PubMed PMID: 1882003): 51-56https://doi.org/10.1007/BF02244553
        View in Article
        • Wenzel JM
        • Cheer JF.
        Endocannabinoid Regulation of Reward and Reinforcement through Interaction with Dopamine and Endogenous Opioid Signaling.
        Neuropsychopharmacology. 2018; 43 (Epub 2017/06/28PubMed PMID: 28653666; PubMed Central PMCID: PMCPMC5719091): 103-115https://doi.org/10.1038/npp.2017.126
        View in Article
        • Trang T
        • Al-Hasani R
        • Salvemini D
        • Salter MW
        • Gutstein H
        • Cahill CM.
        Pain and poppies: the good, the bad, and the ugly of opioid analgesics.
        J Neurosci. 2015; 35 (Epub 2015/10/16PubMed PMID: 26468188; PubMed Central PMCID: PMCPMC4604226): 13879-13888https://doi.org/10.1523/JNEUROSCI.2711-15.2015
        View in Article
        • Fields HL
        • Margolis EB.
        Understanding opioid reward.
        Trends Neurosci. 2015; 38 (Epub 2015/02/02PubMed PMID: 25637939; PubMed Central PMCID: PMCPMC4385443): 217-225https://doi.org/10.1016/j.tins.2015.01.002
        View in Article
        • Pilozzi A
        • Carro C
        • Huang X.
        Roles of beta-Endorphin in Stress, Behavior, Neuroinflammation, and Brain Energy Metabolism.
        Int J Mol Sci. 2020; 22 (Epub 2021/01/06PubMed PMID: 33396962; PubMed Central PMCID: PMCPMC7796446)https://doi.org/10.3390/ijms22010338
        View in Article
        • Suh HH
        • Fujimoto JM
        • Tseng LL.
        Differential mechanisms mediating beta-endorphin- and morphine-induced analgesia in mice.
        Eur J Pharmacol. 1989; 168 (Epub 1989/09/01PubMed PMID: 2531093): 61-70https://doi.org/10.1016/0014-2999(89)90633-x
        View in Article
        • Gomes I
        • Sierra S
        • Lueptow L
        • et al.
        Biased signaling by endogenous opioid peptides.
        Proc Natl Acad Sci U S A. 2020; 117 (Epub 2020/05/13PubMed PMID: 32393639; PubMed Central PMCID: PMCPMC7261131): 11820-11828https://doi.org/10.1073/pnas.2000712117
        View in Article
        • Faouzi A
        • Varga BR
        • Majumdar S.
        Biased Opioid Ligands.
        Molecules. 2020; 25 (Epub 2020/09/20PubMed PMID: 32948048; PubMed Central PMCID: PMCPMC7570672)https://doi.org/10.3390/molecules25184257
        View in Article
        • Manglik A
        • Lin H
        • Aryal DK
        • et al.
        Structure-based discovery of opioid analgesics with reduced side effects.
        Nature. 2016; 537 (Epub 2016/08/18PubMed PMID: 27533032; PubMed Central PMCID: PMCPMC5161585): 185-190https://doi.org/10.1038/nature19112
        View in Article
        • Negri A
        • Rives ML
        • Caspers MJ
        • Prisinzano TE
        • Javitch JA
        • Filizola M.
        Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening.
        J Chem Inf Model. 2013; 53 (Epub 2013/03/07PubMed PMID: 23461591; PubMed Central PMCID: PMCPMC3702663): 521-526https://doi.org/10.1021/ci400019t
        View in Article
        • Bohinc BN
        • Gesty-Palmer D.
        Beta-arrestin-biased agonism at the parathyroid hormone receptor uncouples bone formation from bone resorption.
        Endocr Metab Immune Disord Drug Targets. 2011; 11 (Epub 2011/04/12PubMed PMID: 21476967): 112-119https://doi.org/10.2174/187153011795564151
        View in Article
        • Galandrin S
        • Oligny-Longpre G
        • Bouvier M.
        The evasive nature of drug efficacy: implications for drug discovery.
        Trends Pharmacol Sci. 2007; 28 (Epub 2007/07/31PubMed PMID: 17659355): 423-430https://doi.org/10.1016/j.tips.2007.06.005
        View in Article
        • Rankovic Z
        • Brust TF
        • Bohn LM.
        Biased agonism: an emerging paradigm in GPCR drug discovery.
        Bioorg Med Chem Lett. 2016; 26 (Epub 2015/12/29PubMed PMID: 26707396; PubMed Central PMCID: PMCPMC5595354): 241-250https://doi.org/10.1016/j.bmcl.2015.12.024
        View in Article
        • Conibear AE
        • Asghar J
        • Hill R
        • et al.
        A novel G protein-biased agonist at the delta opioid receptor with analgesic efficacy in models of chronic pain.
        J Pharmacol Exp Ther. 2020; 372 (Epub 2019/10/09PubMed PMID: 31594792; PubMed Central PMCID: PMCPMC6978697): 224-236https://doi.org/10.1124/jpet.119.258640
        View in Article
        • Conibear AE
        • Kelly E.
        A biased view of mu-opioid receptors?.
        Mol Pharmacol. 2019; 96 (Epub 2019/06/09PubMed PMID: 31175184; PubMed Central PMCID: PMCPMC6784500): 542-549https://doi.org/10.1124/mol.119.115956
        View in Article
        • Rivero G
        • Llorente J
        • McPherson J
        • et al.
        Endomorphin-2: a biased agonist at the mu-opioid receptor.
        Mol Pharmacol. 2012; 82 (Epub 2012/05/04PubMed PMID: 22553358; PubMed Central PMCID: PMCPMC3400840): 178-188https://doi.org/10.1124/mol.112.078659
        View in Article
        • Filliol D
        • Ghozland S
        • Chluba J
        • et al.
        Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses.
        Nat Genet. 2000; 25 (Epub 2000/06/03PubMed PMID: 10835636): 195-200https://doi.org/10.1038/76061
        View in Article
        • Bruchas MR
        • Land BB
        • Chavkin C.
        The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors.
        Brain Res. 2010; 1314 (Epub 2009/09/01PubMed PMID: 19716811; PubMed Central PMCID: PMCPMC2819621): 44-55https://doi.org/10.1016/j.brainres.2009.08.062
        View in Article
        • Chefer VI
        • Shippenberg TS.
        Augmentation of morphine-induced sensitization but reduction in morphine tolerance and reward in delta-opioid receptor knockout mice.
        Neuropsychopharmacology. 2009; 34 (Epub 2008/08/16PubMed PMID: 18704097; PubMed Central PMCID: PMCPMC2639630): 887-898https://doi.org/10.1038/npp.2008.128
        View in Article
        • Zhu Y
        • King MA
        • Schuller AG
        • et al.
        Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice.
        Neuron. 1999; 24 (Epub 2000/02/17PubMed PMID: 10677041): 243-252https://doi.org/10.1016/s0896-6273(00)80836-3
        View in Article
        • Konig M
        • Zimmer AM
        • Steiner H
        • et al.
        Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin.
        Nature. 1996; 383 (Epub 1996/10/10PubMed PMID: 8849726): 535-538https://doi.org/10.1038/383535a0
        View in Article
        • McLaughlin JP
        • Land BB
        • Li S
        • Pintar JE
        • Chavkin C.
        Prior activation of kappa opioid receptors by U50488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning.
        Neuropsychopharmacology. 2006; 31 (Epub 2005/08/27PubMed PMID: 16123754; PubMed Central PMCID: PMCPMC2096772): 787-794https://doi.org/10.1038/sj.npp.1300860
        View in Article
        • Volkow ND
        • McLellan AT.
        Opioid abuse in chronic pain–misconceptions and mitigation strategies.
        N Engl J Med. 2016; 374 (Epub 2016/03/31PubMed PMID: 27028915): 1253-1263https://doi.org/10.1056/NEJMra1507771
        View in Article
        • Carroll IR
        • Angst MS
        • Clark JD.
        Management of perioperative pain in patients chronically consuming opioids.
        Reg Anesth Pain Med. 2004; 29 (Epub 2005/01/07PubMed PMID: 15635517): 576-591https://doi.org/10.1016/j.rapm.2004.06.009
        View in Article
        • Morgan MM
        • Christie MJ.
        Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.
        Br J Pharmacol. 2011; 164 (Epub 2011/03/26PubMed PMID: 21434879; PubMed Central PMCID: PMCPMC3229764): 1322-1334https://doi.org/10.1111/j.1476-5381.2011.01335.x
        View in Article
        • Madariaga-Mazon A
        • Marmolejo-Valencia AF
        • Li Y
        • Toll L
        • Houghten RA
        • Martinez-Mayorga K.
        Mu-Opioid receptor biased ligands: a safer and painless discovery of analgesics?.
        Drug Discov Today. 2017; 22 (Epub 2017/07/27PubMed PMID: 28743488; PubMed Central PMCID: PMCPMC6620030): 1719-1729https://doi.org/10.1016/j.drudis.2017.07.002
        View in Article
        • Bohn LM
        • Lefkowitz RJ
        • Gainetdinov RR
        • Peppel K
        • Caron MG
        • Lin FT.
        Enhanced morphine analgesia in mice lacking beta-arrestin 2.
        Science. 1999; 286 (Epub 2000/01/05PubMed PMID: 10617462): 2495-2498https://doi.org/10.1126/science.286.5449.2495
        View in Article
        • Bohn LM
        • Gainetdinov RR
        • Lin FT
        • Lefkowitz RJ
        • Caron MG.
        Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence.
        Nature. 2000; 408 (Epub 2000/12/29PubMed PMID: 11130073): 720-723https://doi.org/10.1038/35047086
        View in Article
        • Kliewer A
        • Schmiedel F
        • Sianati S
        • et al.
        Phosphorylation-deficient G-protein-biased mu-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects.
        Nat Commun. 2019; 10 (Epub 2019/01/22PubMed PMID: 30664663; PubMed Central PMCID: PMCPMC6341117): 367https://doi.org/10.1038/s41467-018-08162-1
        View in Article
        • Gillis A
        • Kliewer A
        • Kelly E
        • et al.
        Critical assessment of G protein-biased agonism at the mu-opioid receptor.
        Trends Pharmacol Sci. 2020; 41 (Epub 2020/10/25PubMed PMID: 33097283): 947-959https://doi.org/10.1016/j.tips.2020.09.009
        View in Article
        • Avidor-Reiss T
        • Nevo I
        • Saya D
        • Bayewitch M
        • Vogel Z.
        Opiate-induced adenylyl cyclase superactivation is isozyme-specific.
        J Biol Chem. 1997; 272 (Epub 1997/02/21PubMed PMID: 9030567): 5040-5047https://doi.org/10.1074/jbc.272.8.5040
        View in Article
        • Sriram K
        • Insel PA.G
        Protein-coupled receptors as targets for approved drugs: how many targets and how many drugs?.
        Mol Pharmacol. 2018; 93 (Epub 2018/01/05PubMed PMID: 29298813; PubMed Central PMCID: PMCPMC5820538): 251-258https://doi.org/10.1124/mol.117.111062
        View in Article
        • Dessauer CW
        • Tesmer JJ
        • Sprang SR
        • Gilman AG.
        Identification of a Gialpha binding site on type V adenylyl cyclase.
        J Biol Chem. 1998; 273 (Epub 1998/09/25PubMed PMID: 9748257): 25831-25839https://doi.org/10.1074/jbc.273.40.25831
        View in Article
        • Defer N
        • Best-Belpomme M
        • Hanoune J.
        Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase.
        Am J Physiol Renal Physiol. 2000; 279 (Epub 2000/09/01PubMed PMID: 10966920): F400-F416https://doi.org/10.1152/ajprenal.2000.279.3.F400
        View in Article
        • Visel A
        • Alvarez-Bolado G
        • Thaller C
        • Eichele G.
        Comprehensive analysis of the expression patterns of the adenylate cyclase gene family in the developing and adult mouse brain.
        J Comp Neurol. 2006; 496 (Epub 2006/04/15PubMed PMID: 16615126): 684-697https://doi.org/10.1002/cne.20953
        View in Article
        • Johansen JP
        • Cain CK
        • Ostroff LE
        • LeDoux JE.
        Molecular mechanisms of fear learning and memory.
        Cell. 2011; 147 (Epub 2011/11/01PubMed PMID: 22036561; PubMed Central PMCID: PMCPMC3215943): 509-524https://doi.org/10.1016/j.cell.2011.10.009
        View in Article
        • Ji RR
        • Xu ZZ
        • Gao YJ.
        Emerging targets in neuroinflammation-driven chronic pain.
        Nat Rev Drug Discov. 2014; 13 (Epub 2014/06/21PubMed PMID: 24948120; PubMed Central PMCID: PMCPMC4228377): 533-548https://doi.org/10.1038/nrd4334
        View in Article
        • Savai R
        • Pullamsetti SS
        • Banat GA
        • et al.
        Targeting cancer with phosphodiesterase inhibitors.
        Expert Opin Investig Drugs. 2010; 19 (Epub 2009/12/17PubMed PMID: 20001559): 117-131https://doi.org/10.1517/13543780903485642
        View in Article
        • Ahmad F
        • Murata T
        • Shimizu K
        • Degerman E
        • Maurice D
        • Manganiello V.
        Cyclic nucleotide phosphodiesterases: important signaling modulators and therapeutic targets.
        Oral Dis. 2015; 21 (Epub 2014/07/25PubMed PMID: 25056711; PubMed Central PMCID: PMCPMC4275405): e25-e50https://doi.org/10.1111/odi.12275
        View in Article
        • Kim C
        • Cheng CY
        • Saldanha SA
        • Taylor SS.
        PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.
        Cell. 2007; 130 (Epub 2007/09/25PubMed PMID: 17889648): 1032-1043https://doi.org/10.1016/j.cell.2007.07.018
        View in Article
        • Sassone-Corsi P.
        The cyclic AMP pathway.
        Cold Spring Harb Perspect Biol. 2012; 4 (Epub 2012/12/05PubMed PMID: 23209152; PubMed Central PMCID: PMCPMC3504441)https://doi.org/10.1101/cshperspect.a011148
        View in Article
        • Mayr B
        • Montminy M.
        Transcriptional regulation by the phosphorylation-dependent factor CREB.
        Nat Rev Mol Cell Biol. 2001; 2 (Epub 2001/08/03PubMed PMID: 11483993): 599-609https://doi.org/10.1038/35085068
        View in Article
        • Bie B
        • Peng Y
        • Zhang Y
        • Pan ZZ.
        cAMP-mediated mechanisms for pain sensitization during opioid withdrawal.
        J Neurosci. 2005; 25 (Epub 2005/04/15PubMed PMID: 15829634; PubMed Central PMCID: PMCPMC6724939): 3824-3832https://doi.org/10.1523/JNEUROSCI.5010-04.2005
        View in Article
        • Barco A
        • Alarcon JM
        • Kandel ER.
        Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture.
        Cell. 2002; 108 (Epub 2002/03/15PubMed PMID: 11893339): 689-703https://doi.org/10.1016/s0092-8674(02)00657-8
        View in Article
        • Williams JT
        • Christie MJ
        • Manzoni O.
        Cellular and synaptic adaptations mediating opioid dependence.
        Physiol Rev. 2001; 81 (Epub 2001/01/12PubMed PMID: 11152760): 299-343https://doi.org/10.1152/physrev.2001.81.1.299
        View in Article
        • Chan P
        • Lutfy K.
        Molecular changes in opioid addiction: the role of adenylyl cyclase and cAMP/PKA system.
        Prog Mol Biol Transl Sci. 2016; 137 (Epub 2016/01/27PubMed PMID: 26810003): 203-227https://doi.org/10.1016/bs.pmbts.2015.10.005
        View in Article
        • Liu JG
        • Anand KJ.
        Protein kinases modulate the cellular adaptations associated with opioid tolerance and dependence.
        Brain Res Brain Res Rev. 2001; 38 (Epub 2001/12/26.PubMed PMID: 11750924): 1-19https://doi.org/10.1016/s0165-0173(01)00057-1
        View in Article
        • Avidor-Reiss T
        • Nevo I
        • Levy R
        • Pfeuffer T
        • Vogel Z.
        Chronic opioid treatment induces adenylyl cyclase V superactivation. Involvement of Gbetagamma.
        J Biol Chem. 1996; 271 (Epub 1996/08/30PubMed PMID: 8702909): 21309-21315https://doi.org/10.1074/jbc.271.35.21309
        View in Article
        • Sharma SK
        • Klee WA
        • Nirenberg M.
        Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance.
        Proc Natl Acad Sci U S A. 1975; 72 (Epub 1975/08/01PubMed PMID: 1059094; PubMed Central PMCID: PMCPMC432926): 3092-3096https://doi.org/10.1073/pnas.72.8.3092
        View in Article
        • Law PY
        • Loh HH.
        delta-Opioid receptor activates cAMP phosphodiesterase activities in neuroblastoma x glioma NG108-15 hybrid cells.
        Mol Pharmacol. 1993; 43 (Epub 1993/05/01. PubMed PMID: 8388986): 684-693
        View in Article
        • Ammer H
        • Schulz R.
        Morphine dependence in human neuroblastoma SH-SY5Y cells is associated with adaptive changes in both the quantity and functional interaction of PGE1 receptors and stimulatory G proteins.
        Brain Res. 1996; 707 (Epub 1996/01/29PubMed PMID: 8919301): 235-244https://doi.org/10.1016/0006-8993(95)01265-6
        View in Article
        • Brust TF
        • Conley JM
        • Watts VJ.
        Galpha(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later.
        Eur J Pharmacol. 2015; 763 (Epub 2015/05/20PubMed PMID: 25981304; PubMed Central PMCID: PMCPMC4584185): 223-232https://doi.org/10.1016/j.ejphar.2015.05.014
        View in Article
        • Watts VJ
        • Neve KA.
        Sensitization of adenylate cyclase by Galpha i/o-coupled receptors.
        Pharmacol Ther. 2005; 106 (Epub 2005/06/01PubMed PMID: 15922020): 405-421https://doi.org/10.1016/j.pharmthera.2004.12.005
        View in Article
        • Taussig R
        • Tang WJ
        • Hepler JR
        • Gilman AG.
        Distinct patterns of bidirectional regulation of mammalian adenylyl cyclases.
        J Biol Chem. 1994; 269 (Epub 1994/02/25. PubMed PMID: 8119955): 6093-6100
        View in Article
        • Ferguson GD
        • Storm DR.
        Why calcium-stimulated adenylyl cyclases?.
        Physiology (Bethesda). 2004; 19 (Epub 2004/09/24PubMed PMID: 15381755): 271-276https://doi.org/10.1152/physiol.00010.2004
        View in Article
        • Zachariou V
        • Liu R
        • LaPlant Q
        • et al.
        Distinct roles of adenylyl cyclases 1 and 8 in opiate dependence: behavioral, electrophysiological, and molecular studies.
        Biol Psychiatry. 2008; 63 (Epub 2008/01/29PubMed PMID: 18222416; PubMed Central PMCID: PMCPMC2442273): 1013-1021https://doi.org/10.1016/j.biopsych.2007.11.021
        View in Article
        • Li S
        • Lee ML
        • Bruchas MR
        • Chan GC
        • Storm DR
        • Chavkin C.
        Calmodulin-stimulated adenylyl cyclase gene deletion affects morphine responses.
        Mol Pharmacol. 2006; 70 (Epub 2006/08/18PubMed PMID: 16914643): 1742-1749https://doi.org/10.1124/mol.106.025783
        View in Article
        • Miao HH
        • Li XH
        • Chen QY
        • Zhuo M.
        Calcium-stimulated adenylyl cyclase subtype 1 is required for presynaptic long-term potentiation in the insular cortex of adult mice.
        Mol Pain. 2019; 15 (Epub 2019/03/23PubMed PMID: 30900503; PubMed Central PMCID: PMCPMC6480986)1744806919842961https://doi.org/10.1177/1744806919842961
        View in Article
        • Nabavi S
        • Fox R
        • Proulx CD
        • Lin JY
        • Tsien RY
        • Malinow R.
        Engineering a memory with LTD and LTP.
        Nature. 2014; 511 (Epub 2014/06/05PubMed PMID: 24896183; PubMed Central PMCID: PMCPMC4210354): 348-352https://doi.org/10.1038/nature13294
        View in Article
        • Wong ST
        • Athos J
        • Figueroa XA
        • et al.
        Calcium-stimulated adenylyl cyclase activity is critical for hippocampus-dependent long-term memory and late phase LTP.
        Neuron. 1999; 23 (Epub 1999/09/11PubMed PMID: 10482244): 787-798https://doi.org/10.1016/s0896-6273(01)80036-2
        View in Article
        • Chen T
        • O'Den G
        • Song Q
        • Koga K
        • Zhang MM
        • Zhuo M.
        Adenylyl cyclase subtype 1 is essential for late-phase long term potentiation and spatial propagation of synaptic responses in the anterior cingulate cortex of adult mice.
        Mol Pain. 2014; 10 (Epub 2014/10/12PubMed PMID: 25304256; PubMed Central PMCID: PMCPMC4198686): 65https://doi.org/10.1186/1744-8069-10-65
        View in Article
        • Yamanaka M
        • Matsuura T
        • Pan H
        • Zhuo M.
        Calcium-stimulated adenylyl cyclase subtype 1 (AC1) contributes to LTP in the insular cortex of adult mice.
        Heliyon. 2017; 3 (Epub 2017/07/20PubMed PMID: 28721398; PubMed Central PMCID: PMCPMC5498404): e00338https://doi.org/10.1016/j.heliyon.2017.e00338
        View in Article
        • Starr CJ
        • Sawaki L
        • Wittenberg GF
        • et al.
        Roles of the insular cortex in the modulation of pain: insights from brain lesions.
        J Neurosci. 2009; 29 (Epub 2009/03/06PubMed PMID: 19261863; PubMed Central PMCID: PMCPMC2748680): 2684-2694https://doi.org/10.1523/JNEUROSCI.5173-08.2009
        View in Article
        • Wieczorek L
        • Majumdar D
        • Wills TA
        • et al.
        Absence of Ca2+-stimulated adenylyl cyclases leads to reduced synaptic plasticity and impaired experience-dependent fear memory.
        Transl Psychiatry. 2012; 2 (Epub 2012/07/27PubMed PMID: 22832970; PubMed Central PMCID: PMCPMC3365269): e126https://doi.org/10.1038/tp.2012.50
        View in Article
        • Liu SB
        • Wang XS
        • Yue J
        • et al.
        Cyclic AMP-dependent positive feedback signaling pathways in the cortex contributes to visceral pain.
        J Neurochem. 2020; 153 (Epub 2019/10/31PubMed PMID: 31665810): 252-263https://doi.org/10.1111/jnc.14903
        View in Article
        • Wang H
        • Gong B
        • Vadakkan KI
        • Toyoda H
        • Kaang BK
        • Zhuo M.
        Genetic evidence for adenylyl cyclase 1 as a target for preventing neuronal excitotoxicity mediated by N-methyl-D-aspartate receptors.
        J Biol Chem. 2007; 282 (Epub 2006/11/24PubMed PMID: 17121841): 1507-1517https://doi.org/10.1074/jbc.M607291200
        View in Article
        • Kang WB
        • Yang Q
        • Guo YY
        • et al.
        Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model.
        Mol Pain. 2016; 12 (Epub 2016/09/11PubMed PMID: 27612915; PubMed Central PMCID: PMCPMC5019365)https://doi.org/10.1177/1744806916652409
        View in Article
        • Cali JJ
        • Zwaagstra JC
        • Mons N
        • Cooper DM
        • Krupinski J.
        Type VIII adenylyl cyclase. A Ca2+/calmodulin-stimulated enzyme expressed in discrete regions of rat brain.
        J Biol Chem. 1994; 269 (Epub 1994/04/22. PubMed PMID: 8163524): 12190-12195
        View in Article
        • Lubker C
        • Seifert R.
        Effects of 39 compounds on calmodulin-regulated adenylyl cyclases AC1 and bacillus anthracis edema factor.
        PLoS One. 2015; 10 (Epub 2015/05/07PubMed PMID: 25946093; PubMed Central PMCID: PMCPMC4422518)e0124017https://doi.org/10.1371/journal.pone.0124017
        View in Article
        • Seifert R
        • Lushington GH
        • Mou TC
        • Gille A
        • Sprang SR.
        Inhibitors of membranous adenylyl cyclases.
        Trends Pharmacol Sci. 2012; 33 (Epub 2011/11/22PubMed PMID: 22100304; PubMed Central PMCID: PMCPMC3273670): 64-78https://doi.org/10.1016/j.tips.2011.10.006
        View in Article
        • Gille A
        • Seifert R.
        2 '(3 ')-O-(N-methylanthraniloyl)-substituted GTP analogs: a novel class of potent competitive adenylyl cyclase inhibitors.
        J Biol Chem. 2003; 278 (Epub 2003/02/05PubMed PMID: 12566433): 12672-12679https://doi.org/10.1074/jbc.M211292200
        View in Article
        • Brand CS
        • Hocker HJ
        • Gorfe AA
        • Cavasotto CN
        • Dessauer CW.
        Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds.
        J Pharmacol Exp Ther. 2013; 347 (Epub 2013/09/06PubMed PMID: 24006339; PubMed Central PMCID: PMCPMC3807061): 265-275https://doi.org/10.1124/jpet.113.208157
        View in Article
        • Tesmer JJ
        • Dessauer CW
        • Sunahara RK
        • et al.
        Molecular basis for P-site inhibition of adenylyl cyclase.
        Biochemistry. 2000; 39 (Epub 2000/11/23PubMed PMID: 11087399): 14464-14471https://doi.org/10.1021/bi0015562
        View in Article
        • Dessauer CW
        • Tesmer JJ
        • Sprang SR
        • Gilman AG.
        The interactions of adenylate cyclases with P-site inhibitors.
        Trends Pharmacol Sci. 1999; 20 (Epub 1999/06/04PubMed PMID: 10354616): 205-210https://doi.org/10.1016/s0165-6147(99)01310-3
        View in Article
        • Haslam RJ
        • Davidson MM
        • Desjardins JV.
        Inhibition of adenylate cyclase by adenosine analogues in preparations of broken and intact human platelets. Evidence for the unidirectional control of platelet function by cyclic AMP.
        Biochem J. 1978; 176 (Epub 1978/10/15PubMed PMID: 215136; PubMed Central PMCID: PMCPMC1186207): 83-95https://doi.org/10.1042/bj1760083
        View in Article
        • Emery AC
        • Eiden MV
        • Eiden LE.
        A new site and mechanism of action for the widely used adenylate cyclase inhibitor SQ22536.
        Mol Pharmacol. 2013; 83 (Epub 2012/10/12PubMed PMID: 23053667; PubMed Central PMCID: PMCPMC3533470): 95-105https://doi.org/10.1124/mol.112.081760
        View in Article
        • Erdorf M
        • Mou TC
        • Seifert R.
        Impact of divalent metal ions on regulation of adenylyl cyclase isoforms by forskolin analogs.
        Biochem Pharmacol. 2011; 82 (Epub 2011/08/17PubMed PMID: 21843517; PubMed Central PMCID: PMCPMC5360100): 1673-1681https://doi.org/10.1016/j.bcp.2011.07.099
        View in Article
        • Haunso A
        • Simpson J
        • Antoni FA.
        Small ligands modulating the activity of mammalian adenylyl cyclases: a novel mode of inhibition by calmidazolium.
        Mol Pharmacol. 2003; 63 (Epub 2003/02/28PubMed PMID: 12606770): 624-631https://doi.org/10.1124/mol.63.3.624
        View in Article
        • Sethna F
        • Feng W
        • Ding Q
        • Robison AJ
        • Feng Y
        • Wang H.
        Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model.
        Nat Commun. 2017; 8 (Epub 2017/02/22PubMed PMID: 28218269; PubMed Central PMCID: PMCPMC5321753): 14359https://doi.org/10.1038/ncomms14359
        View in Article
        • Tian Z
        • Wang DS
        • Wang XS
        • et al.
        Analgesic effects of NB001 on mouse models of arthralgia.
        Mol Brain. 2015; 8 (Epub 2015/10/11PubMed PMID: 26452469; PubMed Central PMCID: PMCPMC4599030): 60https://doi.org/10.1186/s13041-015-0151-9
        View in Article
        • Hayes MP
        • Soto-Velasquez M
        • Fowler CA
        • Watts VJ
        • Roman DL.
        Identification of FDA-approved small molecules capable of disrupting the calmodulin-adenylyl cyclase 8 interaction through direct binding to calmodulin.
        ACS Chem Neurosci. 2018; 9 (Epub 2017/10/03PubMed PMID: 28968502; PubMed Central PMCID: PMCPMC6362833): 346-357https://doi.org/10.1021/acschemneuro.7b00349
        View in Article
        • Ahlijanian MK
        • Cooper DM.
        Antagonism of calmodulin-stimulated adenylate cyclase by trifluoperazine, calmidazolium and W-7 in rat cerebellar membranes.
        J Pharmacol Exp Ther. 1987; 241 (Epub 1987/05/01. PubMed PMID: 3106618): 407-414
        View in Article
        • Brust TF
        • Alongkronrusmee D
        • Soto-Velasquez M
        • et al.
        Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties.
        Sci Signal. 2017; 10 (Epub 2017/02/23PubMed PMID: 28223412; PubMed Central PMCID: PMCPMC5734633)https://doi.org/10.1126/scisignal.aah5381
        View in Article
        • Kaur J
        • Soto-Velasquez M
        • Ding Z
        • et al.
        Optimization of a 1,3,4-oxadiazole series for inhibition of Ca(2+)/calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain.
        Eur J Med Chem. 2019; 162 (Epub 2018/11/26PubMed PMID: 30472604; PubMed Central PMCID: PMCPMC6310635): 568-585https://doi.org/10.1016/j.ejmech.2018.11.036
        View in Article
        • Soto-Velasquez M
        • Hayes MP
        • Alpsoy A
        • Dykhuizen EC
        • Watts VJ.
        A Novel CRISPR/Cas9-based cellular model to explore adenylyl cyclase and cAMP signaling.
        Mol Pharmacol. 2018; 94 (Epub 2018/06/29PubMed PMID: 29950405; PubMed Central PMCID: PMCPMC6064782): 963-972https://doi.org/10.1124/mol.118.111849
        View in Article
        • Mann L
        • Heldman E
        • Bersudsky Y
        • et al.
        Inhibition of specific adenylyl cyclase isoforms by lithium and carbamazepine, but not valproate, may be related to their antidepressant effect.
        Bipolar Disord. 2009; 11 (Epub 2009/11/20PubMed PMID: 19922557): 885-896https://doi.org/10.1111/j.1399-5618.2009.00762.x
        View in Article
        • Pinto C
        • Papa D
        • Hubner M
        • Mou TC
        • Lushington GH
        • Seifert R.
        Activation and inhibition of adenylyl cyclase isoforms by forskolin analogs.
        J Pharmacol Exp Ther. 2008; 325 (Epub 2008/01/11PubMed PMID: 18184830): 27-36https://doi.org/10.1124/jpet.107.131904
        View in Article
        • Iversen L
        • Chapman V.
        Cannabinoids: a real prospect for pain relief?.
        Curr Opin Pharmacol. 2002; 2 (Epub 2002/01/12PubMed PMID: 11786308): 50-55https://doi.org/10.1016/s1471-4892(01)00120-5
        View in Article
        • Manzanares J
        • Julian M
        • Carrascosa A.
        Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes.
        Curr Neuropharmacol. 2006; 4 (Epub 2008/07/11PubMed PMID: 18615144; PubMed Central PMCID: PMCPMC2430692): 239-257https://doi.org/10.2174/157015906778019527
        View in Article
        • Rahn EJ
        • Hohmann AG.
        Cannabinoids as pharmacotherapies for neuropathic pain: from the bench to the bedside.
        Neurotherapeutics. 2009; 6 (Epub 2009/10/01PubMed PMID: 19789075; PubMed Central PMCID: PMCPMC2755639): 713-737https://doi.org/10.1016/j.nurt.2009.08.002
        View in Article
        • Manning BH
        • Martin WJ
        • Meng ID.
        The rodent amygdala contributes to the production of cannabinoid-induced antinociception.
        Neuroscience. 2003; 120 (Epub 2003/08/21PubMed PMID: 12927220): 1157-1170https://doi.org/10.1016/s0306-4522(03)00356-7
        View in Article
        • Cichewicz DL.
        Synergistic interactions between cannabinoid and opioid analgesics.
        Life Sci. 2004; 74 (Epub 2004/01/07PubMed PMID: 14706563): 1317-1324https://doi.org/10.1016/j.lfs.2003.09.038
        View in Article
        • Welch SP.
        Interaction of the cannabinoid and opioid systems in the modulation of nociception.
        Int Rev Psychiatry. 2009; 21 (Epub 2009/04/16PubMed PMID: 19367508): 143-151https://doi.org/10.1080/09540260902782794
        View in Article
        • Desroches J
        • Beaulieu P.
        Opioids and cannabinoids interactions: involvement in pain management.
        Curr Drug Targets. 2010; 11 (Epub 2009/12/19.PubMed PMID: 20017728): 462-473https://doi.org/10.2174/138945010790980303
        View in Article
        • Knezevic NN
        • Jovanovic F
        • Voronov D
        • Candido KD.
        Do corticosteroids still have a place in the treatment of chronic pain?.
        Front Pharmacol. 2018; 9 (Epub 2018/11/18PubMed PMID: 30443214; PubMed Central PMCID: PMCPMC6221932): 1229https://doi.org/10.3389/fphar.2018.01229
        View in Article
        • Mensah-Nyagan AG
        • Meyer L
        • Schaeffer V
        • Kibaly C
        • Patte-Mensah C.
        Evidence for a key role of steroids in the modulation of pain.
        Psychoneuroendocrinology. 2009; 34 (Epub 2009/07/07PubMed PMID: 19577851): S169-S177https://doi.org/10.1016/j.psyneuen.2009.06.004
        View in Article
        • Javan M
        • Kazemi B
        • Ahmadiani A
        • Motamedi F.
        Dexamethasone mimics the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia and compensates for morphine induced changes in G proteins gene expression.
        Brain Res. 2006; 1104 (Epub 2006/07/11PubMed PMID: 16828064): 73-79https://doi.org/10.1016/j.brainres.2006.05.088
        View in Article
        • Nestler EJ
        • Hope BT
        • Widnell KL.
        Drug addiction: a model for the molecular basis of neural plasticity.
        Neuron. 1993; 11 (Epub 1993/12/01PubMed PMID: 8274284): 995-1006https://doi.org/10.1016/0896-6273(93)90213-b
        View in Article
        • Gao W
        • Ren Y
        • Cui GX.
        Dexamethasone added to local lidocaine for infiltration along the spinal-epidural needle pathway decreases incidence and severity of backache after gynecological surgery.
        Med Sci Monit. 2015; 21 (Epub 2015/03/19PubMed PMID: 25785683; PubMed Central PMCID: PMCPMC4374485): 821-827https://doi.org/10.12659/MSM.892620
        View in Article
        • Manchikanti L
        • Pampati V
        • Benyamin RM
        • Boswell MV.
        Analysis of efficacy differences between caudal and lumbar interlaminar epidural injections in chronic lumbar axial discogenic pain: local anesthetic alone vs. local combined with steroids.
        Int J Med Sci. 2015; 12 (Epub 2015/02/14PubMed PMID: 25678838; PubMed Central PMCID: PMCPMC4323359): 214-222https://doi.org/10.7150/ijms.10870
        View in Article
        • Mendez-Resendiz KA
        • Enciso-Pablo O
        • Gonzalez-Ramirez R
        • Juarez-Contreras R
        • Rosenbaum T
        • Morales-Lazaro SL.
        Steroids and TRP channels: a close relationship.
        Int J Mol Sci. 2020; 21 (Epub 2020/05/31PubMed PMID: 32471309; PubMed Central PMCID: PMCPMC7325571)https://doi.org/10.3390/ijms21113819
        View in Article
        • Petrofsky JS
        • Laymon M
        • Alshammari F
        • Khowailed IA
        • Lee H.
        Use of low level of continuous heat and Ibuprofen as an adjunct to physical therapy improves pain relief, range of motion and the compliance for home exercise in patients with nonspecific neck pain: a randomized controlled trial.
        J Back Musculoskelet Rehabil. 2017; 30 (Epub 2017/03/12PubMed PMID: 28282796): 889-896https://doi.org/10.3233/BMR-160577
        View in Article
        • Bedaiwi MK
        • Sari I
        • Wallis D
        • et al.
        Clinical efficacy of celecoxib compared to acetaminophen in chronic nonspecific low back pain: results of a randomized controlled trial.
        Arthritis Care Res (Hoboken). 2016; 68 (Epub 2015/10/17PubMed PMID: 26474041): 845-852https://doi.org/10.1002/acr.22753
        View in Article
        • Ahmed SU
        • Zhang Y
        • Chen L
        • et al.
        Effect of 1.5% topical diclofenac on clinical neuropathic pain.
        Anesthesiology. 2015; 123 (Epub 2015/05/09PubMed PMID: 25955980): 191-198https://doi.org/10.1097/ALN.0000000000000693
        View in Article
        • Sanders D
        • Krause K
        • O'Muircheartaigh J
        • et al.
        Pharmacologic modulation of hand pain in osteoarthritis: a double-blind placebo-controlled functional magnetic resonance imaging study using naproxen.
        Arthritis Rheumatol. 2015; 67 (Epub 2014/12/24PubMed PMID: 25533872; PubMed Central PMCID: PMCPMC4365729): 741-751https://doi.org/10.1002/art.38987
        View in Article
        • Robertson K
        • Marshman LAG
        • Plummer D
        • Downs E.
        Effect of gabapentin vs pregabalin on pain intensity in adults with chronic sciatica: a randomized clinical trial.
        JAMA Neurol. 2019; 76 (Epub 2018/10/17PubMed PMID: 30326006; PubMed Central PMCID: PMCPMC6439871): 28-34https://doi.org/10.1001/jamaneurol.2018.3077
        View in Article
        • Mishra S
        • Bhatnagar S
        • Goyal GN
        • Rana SP
        • Upadhya SP.
        A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study.
        Am J Hosp Palliat Care. 2012; 29 (Epub 2011/07/13PubMed PMID: 21745832): 177-182https://doi.org/10.1177/1049909111412539
        View in Article
        • Salinas FA
        • Lugo LH
        • Garcia HI.
        Efficacy of early treatment with carbamazepine in prevention of neuropathic pain in patients with spinal cord injury.
        Am J Phys Med Rehabil. 2012; 91 (Epub 2012/08/03PubMed PMID: 22854901): 1020-1027https://doi.org/10.1097/PHM.0b013e3182643c85
        View in Article
        • Maarrawi J
        • Abdel Hay J
        • Kobaiter-Maarrawi S
        • Tabet P
        • Peyron R
        • Garcia-Larrea L
        Randomized double-blind controlled study of bedtime low-dose amitriptyline in chronic neck pain.
        Eur J Pain. 2018; 22 (Epub 2018/02/13PubMed PMID: 29436064): 1180-1187https://doi.org/10.1002/ejp.1206
        View in Article
        • Xia D
        • Wang P
        • Chen J
        • Wang S
        • Jiang H.
        Fluoxetine ameliorates symptoms of refractory chronic prostatitis/chronic pelvic pain syndrome.
        Chin Med J (Engl). 2011; 124 (Epub 2011/09/22. PubMed PMID: 21933619): 2158-2161
        View in Article
        • Smith EM
        • Pang H
        • Cirrincione C
        • et al.
        Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial.
        JAMA. 2013; 309 (Epub 2013/04/04PubMed PMID: 23549581; PubMed Central PMCID: PMCPMC3912515): 1359-1367https://doi.org/10.1001/jama.2013.2813
        View in Article

      Article info

      Publication history

      Published online: March 13, 2021
      Accepted: March 8, 2021
      Received in revised form: March 6, 2021
      Received: January 16, 2021

      Identification

      DOI: https://doi.org/10.1016/j.trsl.2021.03.008

      Copyright

      © 2021 Elsevier Inc. All rights reserved.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX