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The Delta Opioid Receptor in Pain Control

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Delta Opioid Receptor Pharmacology and Therapeutic Applications

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 247))

Abstract

Nowadays, the delta opioid receptor (DOPr) represents a promising target for the treatment of chronic pain and emotional disorders. Despite the fact that they produce limited antinociceptive effects in healthy animals and in most acute pain models, DOPr agonists have shown efficacy in various chronic pain models. In this chapter, we review the progresses that have been made over the last decades in understanding the role played by DOPr in the control of pain. More specifically, the distribution of DOPr within the central nervous system and along pain pathways is presented. We also summarize the literature supporting a role for DOPr in acute, tonic, and chronic pain models, as well as the mechanisms regulating its activity under specific conditions. Finally, novel compounds that have make their way to clinical trials are discussed.

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Notes

  1. 1.

    Migraine is the most common and disabling neurological disorder that occurs as recurrent, pulsatile, episodic headaches with or without aura. It is thought to be the result of trigeminal nerve activation leading to distension in cerebral and meningeal blood vessels. The cortical spreading depression (CSD) is defined as a slowly propagated wave of depolarization originating from the occipital to the frontal part of the brain which is followed by a suppression of brain activity (Goadsby et al. 2009; Olesen et al. 2009).

References

  • Akil H, Owens C, Gutstein H, Taylor L, Curran E, Watson S (1998) Endogenous opioids: overview and current issues. Drug Alcohol Depend 51:127–140

    CAS  PubMed  Google Scholar 

  • Al-Hasani R, Bruchas MR (2011) Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 115:1363–1381

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ansari H, Kouti L (2016) Drug interaction and serotonin toxicity with opioid use: another reason to avoid opioids in headache and migraine treatment. Curr Pain Headache Rep 20:50

    PubMed  Google Scholar 

  • Ansonoff MA, Portoghese PS, Pintar JE (2010) Consequences of opioid receptor mutation on actions of univalent and bivalent kappa and delta ligands. Psychopharmacology 210:161–168

    CAS  PubMed  Google Scholar 

  • Arvidsson U, Dado RJ, Riedl M, Lee JH, Law PY, Loh HH, Elde R, Wessendorf MW (1995) Delta-opioid receptor immunoreactivity: distribution in brainstem and spinal cord, and relationship to biogenic amines and enkephalin. J Neurosci 15:1215–1235

    CAS  PubMed  Google Scholar 

  • Baamonde A, Lastra A, Juarez L, Garcia V, Hidalgo A, Menendez L (2005) Effects of the local administration of selective mu-, delta-and kappa-opioid receptor agonists on osteosarcoma-induced hyperalgesia. Naunyn Schmiedebergs Arch Pharmacol 372:213–219

    CAS  PubMed  Google Scholar 

  • Bardoni R, Tawfik VL, Wang D, Francois A, Solorzano C, Shuster SA, Choudhury P, Betelli C, Cassidy C, Smith K, de Nooij JC, Mennicken F, O’Donnell D, Kieffer BL, Woodbury CJ, Basbaum AI, MacDermott AB, Scherrer G (2014) Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn. Neuron 81:1312–1327

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barn DR, Caulfield WL, Cottney J, McGurk K, Morphy JR, Rankovic Z, Roberts B (2001) Parallel synthesis and biological activity of a new class of high affinity and selective delta-opioid ligand. Bioorg Med Chem 9:2609–2624

    CAS  PubMed  Google Scholar 

  • Beaudry H, Proteau-Gagne A, Li S, Dory Y, Chavkin C, Gendron L (2009) Differential noxious and motor tolerance of chronic delta opioid receptor agonists in rodents. Neuroscience 161:381–391

    CAS  PubMed  PubMed Central  Google Scholar 

  • Beaudry H, Dubois D, Gendron L (2011) Activation of spinal mu- and delta-opioid receptors potently inhibits substance P release induced by peripheral noxious stimuli. J Neurosci 31:13068–13077

    CAS  PubMed  PubMed Central  Google Scholar 

  • Beaudry H, Gendron L, Moron JA (2015a) Implication of delta opioid receptor subtype 2 but not delta opioid receptor subtype 1 in the development of morphine analgesic tolerance in a rat model of chronic inflammatory pain. Eur J Neurosci 41:901–907

    CAS  PubMed  Google Scholar 

  • Beaudry H, Mercier-Blais AA, Delaygue C, Lavoie C, Parent JL, Neugebauer W, Gendron L (2015b) Regulation of mu and delta opioid receptor functions: involvement of cyclin-dependent kinase 5. Br J Pharmacol 172:2573–2587

    CAS  PubMed  PubMed Central  Google Scholar 

  • Becker WJ (2015) Acute migraine treatment in adults. Headache 55:778–793

    PubMed  Google Scholar 

  • Befort K, Mattei MG, Roeckel N, Kieffer B (1994) Chromosomal localization of the delta opioid receptor gene to human 1p34.3-p36.1 and mouse 4D bands by in situ hybridization. Genomics 20:143–145

    CAS  PubMed  Google Scholar 

  • Bhushan RG, Sharma SK, Xie Z, Daniels DJ, Portoghese PS (2004) A bivalent ligand (KDN-21) reveals spinal delta and kappa opioid receptors are organized as heterodimers that give rise to delta(1) and kappa(2) phenotypes. Selective targeting of delta-kappa heterodimers. J Med Chem 47:2969–2972

    CAS  PubMed  Google Scholar 

  • Bie B, Pan ZZ (2007) Trafficking of central opioid receptors and descending pain inhibition. Mol Pain 3:37

    PubMed  PubMed Central  Google Scholar 

  • Bie B, Zhang Z, Cai YQ, Zhu W, Zhang Y, Dai J, Lowenstein CJ, Weinman EJ, Pan ZZ (2010) Nerve growth factor-regulated emergence of functional delta-opioid receptors. J Neurosci 30:5617–5628

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bigal ME, Lipton RB (2008) Excessive acute migraine medication use and migraine progression. Neurology 71:1821–1828

    CAS  PubMed  Google Scholar 

  • Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB (2008) Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 48:1157–1168

    PubMed  Google Scholar 

  • Bilsky EJ, Calderon SN, Wang T, Bernstein RN, Davis P, Hruby VJ, McNutt RW, Rothman RB, Rice KC, Porreca F (1995) SNC 80, a selective, nonpeptidic and systemically active opioid delta agonist. J Pharmacol Exp Ther 273:359–366

    CAS  PubMed  Google Scholar 

  • Bilsky EJ, Bernstein RN, Hruby VJ, Rothman RB, Lai J, Porreca F (1996a) Characterization of antinociception to opioid receptor selective agonists after antisense oligodeoxynucleotide-mediated “knock-down” of opioid receptor in vivo. J Pharmacol Exp Ther 277:491–501

    CAS  PubMed  Google Scholar 

  • Bilsky EJ, Wang T, Lai J, Porreca F (1996b) Selective blockade of peripheral delta opioid agonist induced antinociception by intrathecal administration of delta receptor antisense oligodeoxynucleotide. Neurosci Lett 220:155–158

    CAS  PubMed  Google Scholar 

  • Brackley AD, Gomez R, Akopian AN, Henry MA, Jeske NA (2016) GRK2 constitutively governs peripheral delta opioid receptor activity. Cell Rep 16:2686–2698

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brainin-Mattos J, Smith ND, Malkmus S, Rew Y, Goodman M, Taulane J, Yaksh TL (2006) Cancer-related bone pain is attenuated by a systemically available delta-opioid receptor agonist. Pain 122:174–181

    CAS  PubMed  Google Scholar 

  • Brandt MR, Furness MS, Mello NK, Rice KC, Negus SS (2001) Antinociceptive effects of delta-opioid agonists in Rhesus monkeys: effects on chemically induced thermal hypersensitivity. J Pharmacol Exp Ther 296:939–946

    CAS  PubMed  Google Scholar 

  • Brantl V, Pfeiffer A, Herz A, Henschen A, Lottspeich F (1982) Antinociceptive potencies of beta-casomorphin analogs as compared to their affinities towards mu and delta opiate receptor sites in brain and periphery. Peptides 3:793–797

    CAS  PubMed  Google Scholar 

  • Breslin HJ, Diamond CJ, Kavash RW, Cai C, Dyatkin AB, Miskowski TA, Zhang SP, Wade PR, Hornby PJ, He W (2012) Identification of a dual delta OR antagonist/mu OR agonist as a potential therapeutic for diarrhea-predominant irritable bowel syndrome (IBS-d). Bioorg Med Chem Lett 22:4869–4872

    CAS  PubMed  Google Scholar 

  • Broom DC, Jutkiewicz EM, Folk JE, Traynor JR, Rice KC, Woods JH (2002a) Convulsant activity of a non-peptidic delta-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats. Psychopharmacology 164:42–48

    CAS  PubMed  Google Scholar 

  • Broom DC, Nitsche JF, Pintar JE, Rice KC, Woods JH, Traynor JR (2002b) Comparison of receptor mechanisms and efficacy requirements for delta-agonist-induced convulsive activity and antinociception in mice. J Pharmacol Exp Ther 303:723–729

    CAS  PubMed  Google Scholar 

  • Cahill CM, McClellan KA, Morinville A, Hoffert C, Hubatsch D, O’Donnell D, Beaudet A (2001a) Immunohistochemical distribution of delta opioid receptors in the rat central nervous system: evidence for somatodendritic labeling and antigen-specific cellular compartmentalization. J Comp Neurol 440:65–84

    CAS  PubMed  Google Scholar 

  • Cahill CM, Morinville A, Lee MC, Vincent JP, Collier B, Beaudet A (2001b) Prolonged morphine treatment targets delta opioid receptors to neuronal plasma membranes and enhances delta-mediated antinociception. J Neurosci 21:7598–7607

    CAS  PubMed  Google Scholar 

  • Cahill CM, Morinville A, Hoffert C, O’Donnell D, Beaudet A (2003) Up-regulation and trafficking of delta opioid receptor in a model of chronic inflammation: implications for pain control. Pain 101:199–208

    CAS  PubMed  Google Scholar 

  • Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI (1998) Primary afferent tachykinins are required to experience moderate to intense pain. Nature 392:390–394

    CAS  PubMed  Google Scholar 

  • Charles AC, Baca SM (2013) Cortical spreading depression and migraine. Nat Rev Neurol 9:637–644

    PubMed  Google Scholar 

  • Charles A, Pradhan AA (2016) Delta-opioid receptors as targets for migraine therapy. Curr Opin Neurol 29:314–319

    CAS  PubMed  Google Scholar 

  • Chaturvedi K, Christoffers KH, Singh K, Howells RD (2000) Structure and regulation of opioid receptors. Biopolymers 55:334–346

    CAS  PubMed  Google Scholar 

  • Chen Y, Mestek A, Liu J, Hurley JA, Yu L (1993) Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Mol Pharmacol 44:8–12

    CAS  PubMed  Google Scholar 

  • Cheng PY, Svingos AL, Wang H, Clarke CL, Jenab S, Beczkowska IW, Inturrisi CE, Pickel VM (1995) Ultrastructural immunolabeling shows prominent presynaptic vesicular localization of delta-opioid receptor within both enkephalin- and nonenkephalin-containing axon terminals in the superficial layers of the rat cervical spinal cord. J Neurosci 15:5976–5988

    CAS  PubMed  Google Scholar 

  • Cheng PY, Liu-Chen LY, Pickel VM (1997) Dual ultrastructural immunocytochemical labeling of mu and delta opioid receptors in the superficial layers of the rat cervical spinal cord. Brain Res 778:367–380

    CAS  PubMed  Google Scholar 

  • Chu Sin Chung P, Kieffer BL (2013) Delta opioid receptors in brain function and diseases. Pharmacol Ther 140:112–120

    CAS  PubMed  Google Scholar 

  • Chung MK, Cho YS, Bae YC, Lee J, Zhang X, Ro JY (2014) Peripheral G protein-coupled inwardly rectifying potassium channels are involved in delta-opioid receptor-mediated anti-hyperalgesia in rat masseter muscle. Eur J Pain 18:29–38

    CAS  PubMed  Google Scholar 

  • Chung PC, Boehrer A, Stephan A, Matifas A, Scherrer G, Darcq E, Befort K, Kieffer BL (2015) Delta opioid receptors expressed in forebrain GABAergic neurons are responsible for SNC80-induced seizures. Behav Brain Res 278:429–434

    PubMed  Google Scholar 

  • Comer SD, Hoenicke EM, Sable AI, McNutt RW, Chang KJ, De Costa BR, Mosberg HI, Woods JH (1993) Convulsive effects of systemic administration of the delta opioid agonist BW373U86 in mice. J Pharmacol Exp Ther 267:888–895

    CAS  PubMed  Google Scholar 

  • Commons KG (2003) Translocation of presynaptic delta opioid receptors in the ventrolateral periaqueductal gray after swim stress. J Comp Neurol 464:197–207

    PubMed  Google Scholar 

  • Commons KG, Beck SG, Rudoy C, Van Bockstaele EJ (2001) Anatomical evidence for presynaptic modulation by the delta opioid receptor in the ventrolateral periaqueductal gray of the rat. J Comp Neurol 430:200–208

    CAS  PubMed  Google Scholar 

  • Dado RJ, Law PY, Loh HH, Elde R (1993) Immunofluorescent identification of a delta (delta)-opioid receptor on primary afferent nerve terminals. Neuroreport 5:341–344

    CAS  PubMed  Google Scholar 

  • Daniels DJ, Kulkarni A, Xie Z, Bhushan RG, Portoghese PS (2005a) A bivalent ligand (KDAN-18) containing delta-antagonist and kappa-agonist pharmacophores bridges delta2 and kappa1 opioid receptor phenotypes. J Med Chem 48:1713–1716

    CAS  PubMed  Google Scholar 

  • Daniels DJ, Lenard NR, Etienne CL, Law PY, Roerig SC, Portoghese PS (2005b) Opioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series. Proc Natl Acad Sci U S A 102:19208–19213

    CAS  PubMed  PubMed Central  Google Scholar 

  • Darland T, Heinricher MM, Grandy DK (1998) Orphanin FQ/nociceptin: a role in pain and analgesia, but so much more. Trends Neurosci 21:215–221

    CAS  PubMed  Google Scholar 

  • Desmeules JA, Kayser V, Gacel G, Guilbaud G, Roques BP (1993) The highly selective delta agonist BUBU induces an analgesic effect in normal and arthritic rat and this action is not affected by repeated administration of low doses of morphine. Brain Res 611:243–248

    CAS  PubMed  Google Scholar 

  • Dondio G, Ronzoni S, Farina C, Graziani D, Parini C, Petrillo P, Giardina GA (2001) Selective delta opioid receptor agonists for inflammatory and neuropathic pain. Farmaco 56:117–119

    CAS  PubMed  Google Scholar 

  • Dore-Savard L, Otis V, Belleville K, Lemire M, Archambault M, Tremblay L, Beaudoin JF, Beaudet N, Lecomte R, Lepage M, Gendron L, Sarret P (2010) Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain. PLoS One 5:e13774

    PubMed  PubMed Central  Google Scholar 

  • Dubois D, Gendron L (2010) Delta opioid receptor-mediated analgesia is not altered in preprotachykinin A knockout mice. Eur J Neurosci 32:1921–1929

    PubMed  Google Scholar 

  • Dykstra LA, Schoenbaum GM, Yarbrough J, McNutt R, Chang KJ (1993) A novel delta opioid agonist, BW373U86, in squirrel monkeys responding under a schedule of shock titration. J Pharmacol Exp Ther 267:875–882

    CAS  PubMed  Google Scholar 

  • Evans CJ, Keith DE Jr, Morrison H, Magendzo K, Edwards RH (1992) Cloning of a delta opioid receptor by functional expression. Science 258:1952–1955

    CAS  PubMed  Google Scholar 

  • Fenalti G, Giguere PM, Katritch V, Huang XP, Thompson AA, Cherezov V, Roth BL, Stevens RC (2014) Molecular control of delta-opioid receptor signalling. Nature 506:191–196

    CAS  PubMed  PubMed Central  Google Scholar 

  • Filliol D, Ghozland S, Chluba J, Martin M, Matthes HW, Simonin F, Befort K, Gaveriaux-Ruff C, Dierich A, LeMeur M, Valverde O, Maldonado R, Kieffer BL (2000) Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet 25:195–200

    CAS  PubMed  Google Scholar 

  • Finn AK, Whistler JL (2001) Endocytosis of the mu opioid receptor reduces tolerance and a cellular hallmark of opiate withdrawal. Neuron 32:829–839

    CAS  PubMed  Google Scholar 

  • Fraser GL, Gaudreau GA, Clarke PB, Menard DP, Perkins MN (2000a) Antihyperalgesic effects of delta opioid agonists in a rat model of chronic inflammation. Br J Pharmacol 129:1668–1672

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fraser GL, Holmgren J, Clarke PB, Wahlestedt C (2000b) Antisense inhibition of delta-opioid receptor gene function in vivo by peptide nucleic acids. Mol Pharmacol 57:725–731

    CAS  PubMed  Google Scholar 

  • Fujita W, Gomes I, Devi LA (2014) Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10. Br J Pharmacol 171:4155–4176

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fujita W, Gomes I, Devi LA (2015) Heteromers of mu-delta opioid receptors: new pharmacology and novel therapeutic possibilities. Br J Pharmacol 172:375–387

    CAS  PubMed  Google Scholar 

  • Gallantine EL, Meert TF (2005) A comparison of the antinociceptive and adverse effects of the mu-opioid agonist morphine and the delta-opioid agonist SNC80. Basic Clin Pharmacol Toxicol 97:39–51

    CAS  PubMed  Google Scholar 

  • Garnock-Jones KP (2015) Eluxadoline: first global approval. Drugs 75:1305–1310

    CAS  PubMed  Google Scholar 

  • Gaveriaux-Ruff C, Kieffer BL (2011) Delta opioid receptor analgesia: recent contributions from pharmacology and molecular approaches. Behav Pharmacol 22:405–414

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gaveriaux-Ruff C, Karchewski LA, Hever X, Matifas A, Kieffer BL (2008) Inflammatory pain is enhanced in delta opioid receptor-knockout mice. Eur J Neurosci 27:2558–2567

    PubMed  PubMed Central  Google Scholar 

  • Gaveriaux-Ruff C, Nozaki C, Nadal X, Hever XC, Weibel R, Matifas A, Reiss D, Filliol D, Nassar MA, Wood JN, Maldonado R, Kieffer BL (2011) Genetic ablation of delta opioid receptors in nociceptive sensory neurons increases chronic pain and abolishes opioid analgesia. Pain 152:1238–1248

    CAS  PubMed  Google Scholar 

  • Gendron L, Lucido AL, Mennicken F, O’Donnell D, Vincent JP, Stroh T, Beaudet A (2006) Morphine and pain-related stimuli enhance cell surface availability of somatic delta-opioid receptors in rat dorsal root ganglia. J Neurosci 26:953–962

    CAS  PubMed  Google Scholar 

  • Gendron L, Esdaile MJ, Mennicken F, Pan H, O'Donnell D, Vincent J-P, Devi LA, Cahill CM, Stroh T, Beaudet A (2007a) Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin. Neuroscience 144:263–274

    CAS  PubMed  Google Scholar 

  • Gendron L, Pintar JE, Chavkin C (2007b) Essential role of mu opioid receptor in the regulation of delta opioid receptor-mediated antihyperalgesia. Neuroscience 150:807–817

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gendron L, Mittal N, Beaudry H, Walwyn W (2015) Recent advances on the delta opioid receptor: from trafficking to function. Br J Pharmacol 172:403–419

    CAS  PubMed  Google Scholar 

  • Gendron L, Cahill CM, von Zastrow M, Schiller PW, Pineyro G (2016) Molecular pharmacology of delta-opioid receptors. Pharmacol Rev 68:631–700

    CAS  PubMed  PubMed Central  Google Scholar 

  • George SR, Zastawny RL, Briones-Urbina R, Cheng R, Nguyen T, Heiber M, Kouvelas A, Chan AS, O’Dowd BF (1994) Distinct distributions of mu, delta and kappa opioid receptor mRNA in rat brain. Biochem Biophys Res Commun 205:1438–1444

    CAS  PubMed  Google Scholar 

  • Goadsby PJ, Charbit AR, Andreou AP, Akerman S, Holland PR (2009) Neurobiology of migraine. Neuroscience 161:327–341

    CAS  PubMed  Google Scholar 

  • Goldstein A, Tachibana S, Lowney LI, Hunkapiller M, Hood L (1979) Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci U S A 76:6666–6670

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gomes I, Fujita W, Gupta A, Saldanha SA, Negri A, Pinello CE, Eberhart C, Roberts E, Filizola M, Hodder P, Devi LA (2013) Identification of a mu-delta opioid receptor heteromer-biased agonist with antinociceptive activity. Proc Natl Acad Sci U S A 110:12072–12077

    CAS  PubMed  PubMed Central  Google Scholar 

  • Granier S, Manglik A, Kruse AC, Kobilka TS, Thian FS, Weis WI, Kobilka BK (2012) Structure of the delta-opioid receptor bound to naltrindole. Nature 485:400–404

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guan JS, Xu ZZ, Gao H, He SQ, Ma GQ, Sun T, Wang LH, Zhang ZN, Lena I, Kitchen I, Elde R, Zimmer A, He C, Pei G, Bao L, Zhang X (2005) Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia. Cell 122:619–631

    CAS  PubMed  Google Scholar 

  • Gupta A, Mulder J, Gomes I, Rozenfeld R, Bushlin I, Ong E, Lim M, Maillet E, Junek M, Cahill CM, Harkany T, Devi LA (2010) Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci Signal 3:ra54

    PubMed  PubMed Central  Google Scholar 

  • Hack SP, Bagley EE, Chieng BC, Christie MJ (2005) Induction of delta-opioid receptor function in the midbrain after chronic morphine treatment. J Neurosci 25:3192–3198

    CAS  PubMed  Google Scholar 

  • Hansra P, Moran EL, Fornasier VL, Bogoch ER (2000) Carrageenan-induced arthritis in the rat. Inflammation 24:141–155

    CAS  PubMed  Google Scholar 

  • Harvey JH, Long DH, England PM, Whistler JL (2012) Tuned-affinity bivalent ligands for the characterization of opioid receptor heteromers. ACS Med Chem Lett 3:640–644

    CAS  PubMed  PubMed Central  Google Scholar 

  • Headrick JP, See Hoe LE, Du Toit EF, Peart JN (2015) Opioid receptors and cardioprotection – ‘opioidergic conditioning’ of the heart. Br J Pharmacol 172:2026–2050

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hervera A, Leanez S, Negrete R, Pol O (2009) The peripheral administration of a nitric oxide donor potentiates the local antinociceptive effects of a DOR agonist during chronic inflammatory pain in mice. Naunyn Schmiedebergs Arch Pharmacol 380:345–352

    CAS  PubMed  Google Scholar 

  • Heydorn A, Sondergaard BP, Ersboll B, Holst B, Nielsen FC, Haft CR, Whistler J, Schwartz TW (2004) A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associated sorting protein (GASP). J Biol Chem 279:54291–54303

    CAS  PubMed  Google Scholar 

  • Holdridge SV, Cahill CM (2007) Spinal administration of a delta opioid receptor agonist attenuates hyperalgesia and allodynia in a rat model of neuropathic pain. Eur J Pain 11:685–693

    CAS  PubMed  Google Scholar 

  • Honore P, Rogers SD, Schwei MJ, Salak-Johnson JL, Luger NM, Sabino MC, Clohisy DR, Mantyh PW (2000) Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience 98:585–598

    CAS  PubMed  Google Scholar 

  • Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR (1975) Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258:577–580

    CAS  PubMed  Google Scholar 

  • Hurley RW, Hammond DL (2000) The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 20:1249–1259

    CAS  PubMed  Google Scholar 

  • Hylden JL, Thomas DA, Iadarola MJ, Nahin RL, Dubner R (1991) Spinal opioid analgesic effects are enhanced in a model of unilateral inflammation/hyperalgesia: possible involvement of noradrenergic mechanisms. Eur J Pharmacol 194:135–143

    CAS  PubMed  Google Scholar 

  • Ichikawa H, Schulz S, Hollt V, Sugimoto T (2005) Delta-opioid receptor-immunoreactive neurons in the rat cranial sensory ganglia. Brain Res 1043:225–230

    CAS  PubMed  Google Scholar 

  • Ji RR, Zhang Q, Law PY, Low HH, Elde R, Hokfelt T (1995) Expression of mu-, delta-, and kappa-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation. J Neurosci 15:8156–8166

    CAS  PubMed  Google Scholar 

  • Kabli N, Cahill CM (2007) Anti-allodynic effects of peripheral delta opioid receptors in neuropathic pain. Pain 127:84–93

    CAS  PubMed  Google Scholar 

  • Kamei J, Kashiwazaki T, Hitosugi H, Nagase H (1997a) The role of spinal delta1-opioid receptors in inhibiting the formalin-induced nociceptive response in diabetic mice. Eur J Pharmacol 326:31–36

    CAS  PubMed  Google Scholar 

  • Kamei J, Kawai K, Mizusuna A, Saitoh A, Morita K, Narita M, Tseng LF, Nagase H (1997b) Supraspinal delta 1-opioid receptor-mediated antinociceptive properties of (-)-TAN-67 in diabetic mice. Eur J Pharmacol 322:27–30

    CAS  PubMed  Google Scholar 

  • Kent JL, Pert CB, Herkenham M (1981) Ontogeny of opiate receptors in rat forebrain: visualization by in vitro autoradiography. Brain Res 254:487–504

    CAS  PubMed  Google Scholar 

  • Kieffer BL, Evans CJ (2009) Opioid receptors: from binding sites to visible molecules in vivo. Neuropharmacology 56(Suppl 1):205–212

    CAS  PubMed  Google Scholar 

  • Kieffer BL, Gaveriaux-Ruff C (2002) Exploring the opioid system by gene knockout. Prog Neurobiol 66:285–306

    CAS  PubMed  Google Scholar 

  • Kieffer BL, Befort K, Gaveriaux-Ruff C, Hirth CG (1992) The delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characterization. Proc Natl Acad Sci U S A 89:12048–12052

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klareskog L (1989) What can we learn about rheumatoid arthritis from animal models? Springer Semin Immunopathol 11:315–333

    CAS  PubMed  Google Scholar 

  • Kouchek M, Takasusuki T, Terashima T, Yaksh TL, Xu Q (2013) Effects of intrathecal SNC80, a delta receptor ligand, on nociceptive threshold and dorsal horn substance p release. J Pharmacol Exp Ther 347:258–264

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krames ES, Wilkie DJ, Gershow J (1986) Intrathecal D-Ala2-D-Leu5-enkephalin (DADL) restores analgesia in a patient analgetically tolerant to intrathecal morphine sulfate. Pain 24:205–209

    CAS  PubMed  Google Scholar 

  • Le Bourdonnec B, Windh RT, Ajello CW, Leister LK, Gu M, Chu GH, Tuthill PA, Barker WM, Koblish M, Wiant DD, Graczyk TM, Belanger S, Cassel JA, Feschenko MS, Brogdon BL, Smith SA, Christ DD, Derelanko MJ, Kutz S, Little PJ, DeHaven RN, DeHaven-Hudkins DL, Dolle RE (2008) Potent, orally bioavailable delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-4-(5-hydroxyspiro[chromene-2,4'-piperidine]-4-yl)benzamide (ADL5859). J Med Chem 51:5893–5896

    PubMed  Google Scholar 

  • Le Bourdonnec B, Windh RT, Leister LK, Zhou QJ, Ajello CW, Gu M, Chu GH, Tuthill PA, Barker WM, Koblish M, Wiant DD, Graczyk TM, Belanger S, Cassel JA, Feschenko MS, Brogdon BL, Smith SA, Derelanko MJ, Kutz S, Little PJ, DeHaven RN, DeHaven-Hudkins DL, Dolle RE (2009) Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4′-piperidine]-4-yl) benzamide (ADL5747). J Med Chem 52:5685–5702

    PubMed  Google Scholar 

  • Le Merrer J, Becker JA, Befort K, Kieffer BL (2009) Reward processing by the opioid system in the brain. Physiol Rev 89:1379–1412

    PubMed  PubMed Central  Google Scholar 

  • Lembo AJ, Lacy BE, Zuckerman MJ, Schey R, Dove LS, Andrae DA, Davenport JM, McIntyre G, Lopez R, Turner L, Covington PS (2016) Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med 374:242–253

    CAS  PubMed  Google Scholar 

  • Li CH, Chung D (1976) Isolation and structure of an untriakontapeptide with opiate activity from camel pituitary glands. Proc Natl Acad Sci U S A 73:1145–1148

    CAS  PubMed  PubMed Central  Google Scholar 

  • Loh HH, Tseng LF, Wei E, Li CH (1976) beta-endorphin is a potent analgesic agent. Proc Natl Acad Sci U S A 73:2895–2898

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lucido AL, Morinville A, Gendron L, Stroh T, Beaudet A (2005) Prolonged morphine treatment selectively increases membrane recruitment of delta-opioid receptors in mouse basal ganglia. J Mol Neurosci 25:207–214

    CAS  PubMed  Google Scholar 

  • Lutz PE, Kieffer BL (2013) Opioid receptors: distinct roles in mood disorders. Trends Neurosci 36:195–206

    CAS  PubMed  Google Scholar 

  • Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S (2012) Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature 485:321–326

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ (1987) Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain. J Neurosci 7:2445–2464

    CAS  PubMed  Google Scholar 

  • Mansour A, Thompson RC, Akil H, Watson SJ (1993) Delta opioid receptor mRNA distribution in the brain: comparison to delta receptor binding and proenkephalin mRNA. J Chem Neuroanat 6:351–362

    CAS  PubMed  Google Scholar 

  • Mansour A, Fox CA, Burke S, Meng F, Thompson RC, Akil H, Watson SJ (1994) Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study. J Comp Neurol 350:412–438

    CAS  PubMed  Google Scholar 

  • Mansour A, Fox CA, Akil H, Watson SJ (1995) Opioid-receptor mRNA expression in the rat CNS: anatomical and functional implications. Trends Neurosci 18:22–29

    CAS  PubMed  Google Scholar 

  • McDowell J, Kitchen I (1986) Ontogenesis of delta-opioid receptors in rat brain using [3H][D-Pen2,D-Pen5]enkephalin as a binding ligand. Eur J Pharmacol 128:287–289

    CAS  PubMed  Google Scholar 

  • McQuay H (1999) Opioids in pain management. Lancet 353:2229–2232

    CAS  PubMed  Google Scholar 

  • Meng F, Xie GX, Thompson RC, Mansour A, Goldstein A, Watson SJ, Akil H (1993) Cloning and pharmacological characterization of a rat kappa opioid receptor. Proc Natl Acad Sci U S A 90:9954–9958

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mennicken F, Zhang J, Hoffert C, Ahmad S, Beaudet A, O’Donnell D (2003) Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia. J Comp Neurol 465:349–360

    CAS  PubMed  Google Scholar 

  • Meunier JC, Mollereau C, Toll L, Suaudeau C, Moisand C, Alvinerie P, Butour JL, Guillemot JC, Ferrara P, Monsarrat B et al (1995) Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. Nature 377:532–535

    CAS  PubMed  Google Scholar 

  • Mika J, Przewlocki R, Przewlocka B (2001) The role of delta-opioid receptor subtypes in neuropathic pain. Eur J Pharmacol 415:31–37

    CAS  PubMed  Google Scholar 

  • Milan-Lobo L, Whistler JL (2011) Heteromerization of the mu- and delta-opioid receptors produces ligand-biased antagonism and alters mu-receptor trafficking. J Pharmacol Exp Ther 337:868–875

    CAS  PubMed  PubMed Central  Google Scholar 

  • Milan-Lobo L, Enquist J, van Rijn RM, Whistler JL (2013) Anti-analgesic effect of the mu/delta opioid receptor heteromer revealed by ligand-biased antagonism. PLoS One 8:e58362

    CAS  PubMed  PubMed Central  Google Scholar 

  • Minami M, Toya T, Katao Y, Maekawa K, Nakamura S, Onogi T, Kaneko S, Satoh M (1993) Cloning and expression of a cDNA for the rat kappa-opioid receptor. FEBS Lett 329:291–295

    CAS  PubMed  Google Scholar 

  • Minami M, Maekawa K, Yabuuchi K, Satoh M (1995) Double in situ hybridization study on coexistence of mu-, delta- and kappa-opioid receptor mRNAs with preprotachykinin A mRNA in the rat dorsal root ganglia. Brain Res Mol Brain Res 30:203–210

    CAS  PubMed  Google Scholar 

  • Morinville A, Cahill CM, Esdaile MJ, Aibak H, Collier B, Kieffer BL, Beaudet A (2003) Regulation of delta-opioid receptor trafficking via mu-opioid receptor stimulation: evidence from mu-opioid receptor knock-out mice. J Neurosci 23:4888–4898

    CAS  PubMed  Google Scholar 

  • Morinville A, Cahill CM, Aibak H, Rymar VV, Pradhan A, Hoffert C, Mennicken F, Stroh T, Sadikot AF, O'Donnell D, Clarke PB, Collier B, Henry JL, Vincent JP, Beaudet A (2004) Morphine-induced changes in delta opioid receptor trafficking are linked to somatosensory processing in the rat spinal cord. J Neurosci 24:5549–5559

    CAS  PubMed  Google Scholar 

  • Mosberg HI, Hurst R, Hruby VJ, Gee K, Yamamura HI, Galligan JJ, Burks TF (1983) Bis-penicillamine enkephalins possess highly improved specificity toward delta opioid receptors. Proc Natl Acad Sci U S A 80:5871–5874

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moulin DE, Max MB, Kaiko RF, Inturrisi CE, Maggard J, Yaksh TL, Foley KM (1985) The analgesic efficacy of intrathecal D-Ala2-D-Leu5-enkephalin in cancer patients with chronic pain. Pain 23:213–221

    CAS  PubMed  Google Scholar 

  • Nadal X, Banos JE, Kieffer BL, Maldonado R (2006) Neuropathic pain is enhanced in delta-opioid receptor knockout mice. Eur J Neurosci 23:830–834

    PubMed  Google Scholar 

  • Negri L, Severini C, Lattanzi R, Potenza RL, Melchiorri P (1997) Postnatal development of delta-opioid receptor subtypes in mice. Br J Pharmacol 120:989–994

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nitsche JF, Pintar JE (2003) Opioid receptor-induced GTPgamma35S binding during mouse development. Dev Biol 253:99–108

    CAS  PubMed  Google Scholar 

  • Obara I, Parkitna JR, Korostynski M, Makuch W, Kaminska D, Przewlocka B, Przewlocki R (2009) Local peripheral opioid effects and expression of opioid genes in the spinal cord and dorsal root ganglia in neuropathic and inflammatory pain. Pain 141:283–291

    CAS  PubMed  Google Scholar 

  • Olesen J, Burstein R, Ashina M, Tfelt-Hansen P (2009) Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol 8:679–690

    PubMed  Google Scholar 

  • Onofrio BM, Yaksh TL (1983) Intrathecal delta-receptor ligand produces analgesia in man. Lancet 1:1386–1387

    CAS  PubMed  Google Scholar 

  • Otis V, Sarret P, Gendron L (2011) Spinal activation of delta opioid receptors alleviates cancer-related bone pain. Neuroscience 183:221–229

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pacheco DF, Duarte ID (2005) Delta-opioid receptor agonist SNC80 induces peripheral antinociception via activation of ATP-sensitive K+ channels. Eur J Pharmacol 512:23–28

    CAS  PubMed  Google Scholar 

  • Pakarinen ED, Woods JH, Moerschbaecher JM (1995) Repeated acquisition of behavioral chains in squirrel monkeys: comparisons of a mu, kappa and delta opioid agonist. J Pharmacol Exp Ther 272:552–559

    CAS  PubMed  Google Scholar 

  • Pasquini F, Bochet P, Garbay-Jaureguiberry C, Roques BP, Rossier J, Beaudet A (1992) Electron microscopic localization of photoaffinity-labelled delta opioid receptors in the neostriatum of the rat. J Comp Neurol 326:229–244

    CAS  PubMed  Google Scholar 

  • Patwardhan AM, Berg KA, Akopain AN, Jeske NA, Gamper N, Clarke WP, Hargreaves KM (2005) Bradykinin-induced functional competence and trafficking of the delta-opioid receptor in trigeminal nociceptors. J Neurosci 25:8825–8832

    CAS  PubMed  Google Scholar 

  • Peng J, Sarkar S, Chang SL (2012) Opioid receptor expression in human brain and peripheral tissues using absolute quantitative real-time RT-PCR. Drug Alcohol Depend 124:223–228

    CAS  PubMed  PubMed Central  Google Scholar 

  • Petrillo P, Angelici O, Bingham S, Ficalora G, Garnier M, Zaratin PF, Petrone G, Pozzi O, Sbacchi M, Stean TO, Upton N, Dondio GM, Scheideler MA (2003) Evidence for a selective role of the delta-opioid agonist [8R-(4bS*,8aalpha,8abeta, 12bbeta)]7,10-dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoli ne hydrochloride (SB-235863) in blocking hyperalgesia associated with inflammatory and neuropathic pain responses. J Pharmacol Exp Ther 307:1079–1089

    CAS  PubMed  Google Scholar 

  • Podolsky AT, Sandweiss A, Hu J, Bilsky EJ, Cain JP, Kumirov VK, Lee YS, Hruby VJ, Vardanyan RS, Vanderah TW (2013) Novel fentanyl-based dual mu/delta-opioid agonists for the treatment of acute and chronic pain. Life Sci 93:1010–1016

    CAS  PubMed  PubMed Central  Google Scholar 

  • Porreca F, Mosberg HI, Hurst R, Hruby VJ, Burks TF (1984) Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse. J Pharmacol Exp Ther 230:341–348

    CAS  PubMed  Google Scholar 

  • Poulin JF, Chevalier B, Laforest S, Drolet G (2006) Enkephalinergic afferents of the centromedial amygdala in the rat. J Comp Neurol 496:859–876

    PubMed  Google Scholar 

  • Pradhan AA, Clarke PB (2005) Comparison between delta-opioid receptor functional response and autoradiographic labeling in rat brain and spinal cord. J Comp Neurol 481:416–426

    CAS  PubMed  Google Scholar 

  • Pradhan AA, Siau C, Constantin A, Clarke PB (2006) Chronic morphine administration results in tolerance to delta opioid receptor-mediated antinociception. Neuroscience 141:947–954

    CAS  PubMed  Google Scholar 

  • Pradhan AA, Befort K, Nozaki C, Gaveriaux-Ruff C, Kieffer BL (2011) The delta opioid receptor: an evolving target for the treatment of brain disorders. Trends Pharmacol Sci 32:581–590

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pradhan A, Smith M, McGuire B, Evans C, Walwyn W (2013) Chronic inflammatory injury results in increased coupling of delta opioid receptors to voltage-gated Ca2+ channels. Mol Pain 9:8

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pradhan AA, Smith ML, McGuire B, Tarash I, Evans CJ, Charles A (2014) Characterization of a novel model of chronic migraine. Pain 155:269–274

    CAS  PubMed  Google Scholar 

  • Qiu C, Sora I, Ren K, Uhl G, Dubner R (2000) Enhanced delta-opioid receptor-mediated antinociception in mu-opioid receptor-deficient mice. Eur J Pharmacol 387:163–169

    CAS  PubMed  Google Scholar 

  • Reinscheid RK, Nothacker HP, Bourson A, Ardati A, Henningsen RA, Bunzow JR, Grandy DK, Langen H, Monsma FJ Jr, Civelli O (1995) Orphanin FQ: a neuropeptide that activates an opioidlike G protein-coupled receptor. Science 270:792–794

    CAS  PubMed  Google Scholar 

  • Riedl MS, Schnell SA, Overland AC, Chabot-Dore AJ, Taylor AM, Ribeiro-da-Silva A, Elde RP, Wilcox GL, Stone LS (2009) Coexpression of alpha 2A-adrenergic and delta-opioid receptors in substance P-containing terminals in rat dorsal horn. J Comp Neurol 513:385–398

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rossi GC, Pasternak GW, Bodnar RJ (1994) Mu and delta opioid synergy between the periaqueductal gray and the rostro-ventral medulla. Brain Res 665:85–93

    CAS  PubMed  Google Scholar 

  • Saitoh A, Sugiyama A, Nemoto T, Fujii H, Wada K, Oka J, Nagase H, Yamada M (2011) The novel delta opioid receptor agonist KNT-127 produces antidepressant-like and antinociceptive effects in mice without producing convulsions. Behav Brain Res 223:271–279

    CAS  PubMed  Google Scholar 

  • Saloman JL, Niu KY, Ro JY (2011) Activation of peripheral delta-opioid receptors leads to anti-hyperalgesic responses in the masseter muscle of male and female rats. Neuroscience 190:379–385

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sauriyal DS, Jaggi AS, Singh N (2011) Extending pharmacological spectrum of opioids beyond analgesia: multifunctional aspects in different pathophysiological states. Neuropeptides 45:175–188

    CAS  PubMed  Google Scholar 

  • Scherrer G, Imamachi N, Cao YQ, Contet C, Mennicken F, O’Donnell D, Kieffer BL, Basbaum AI (2009) Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell 137:1148–1159

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sharif NA, Hughes J (1989) Discrete mapping of brain Mu and delta opioid receptors using selective peptides: quantitative autoradiography, species differences and comparison with kappa receptors. Peptides 10:499–522

    CAS  PubMed  Google Scholar 

  • Simonin F, Karcher P, Boeuf JJ, Matifas A, Kieffer BL (2004) Identification of a novel family of G protein-coupled receptor associated sorting proteins. J Neurochem 89:766–775

    CAS  PubMed  Google Scholar 

  • Slowe SJ, Simonin F, Kieffer B, Kitchen I (1999) Quantitative autoradiography of mu-,delta- and kappa1 opioid receptors in kappa-opioid receptor knockout mice. Brain Res 818:335–345

    CAS  PubMed  Google Scholar 

  • Snyder SH, Pasternak GW (2003) Historical review: opioid receptors. Trends Pharmacol Sci 24:198–205

    CAS  PubMed  Google Scholar 

  • Sohn JH, Lee BH, Park SH, Ryu JW, Kim BO, Park YG (2000) Microinjection of opiates into the periaqueductal gray matter attenuates neuropathic pain symptoms in rats. Neuroreport 11:1413–1416

    CAS  PubMed  Google Scholar 

  • Stein C, Lang LJ (2009) Peripheral mechanisms of opioid analgesia. Curr Opin Pharmacol 9:3–8

    CAS  PubMed  Google Scholar 

  • Stein C, Machelska H, Binder W, Schafer M (2001) Peripheral opioid analgesia. Curr Opin Pharmacol 1:62–65

    CAS  PubMed  Google Scholar 

  • Stevens CW (2009) The evolution of vertebrate opioid receptors. Front Biosci (Landmark Ed) 14:1247–1269

    CAS  Google Scholar 

  • Stewart PE, Hammond DL (1994) Activation of spinal delta-1 or delta-2 opioid receptors reduces carrageenan-induced hyperalgesia in the rat. J Pharmacol Exp Ther 268:701–708

    CAS  PubMed  Google Scholar 

  • Suarez-Roca H, Maixner W (1992) Delta-opioid-receptor activation by [D-Pen2,D-Pen5]enkephalin and morphine inhibits substance P release from trigeminal nucleus slices. Eur J Pharmacol 229:1–7

    CAS  PubMed  Google Scholar 

  • Tsao PI, von Zastrow M (2000) Type-specific sorting of G protein-coupled receptors after endocytosis. J Biol Chem 275:11130–11140

    CAS  PubMed  Google Scholar 

  • Wade PR, Palmer JM, McKenney S, Kenigs V, Chevalier K, Moore BA, Mabus JR, Saunders PR, Wallace NH, Schneider CR, Kimball ES, Breslin HJ, He W, Hornby PJ (2012) Modulation of gastrointestinal function by MuDelta, a mixed micro opioid receptor agonist/ micro opioid receptor antagonist. Br J Pharmacol 167:1111–1125

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Pickel VM (2001) Preferential cytoplasmic localization of delta-opioid receptors in rat striatal patches: comparison with plasmalemmal mu-opioid receptors. J Neurosci 21:3242–3250

    CAS  PubMed  Google Scholar 

  • Wang H, Wessendorf MW (2001) Equal proportions of small and large DRG neurons express opioid receptor mRNAs. J Comp Neurol 429:590–600

    CAS  PubMed  Google Scholar 

  • Wang JB, Imai Y, Eppler CM, Gregor P, Spivak CE, Uhl GR (1993) mu opiate receptor: cDNA cloning and expression. Proc Natl Acad Sci U S A 90:10230–10234

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang JB, Johnson PS, Persico AM, Hawkins AL, Griffin CA, Uhl GR (1994) Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. FEBS Lett 338:217–222

    CAS  PubMed  Google Scholar 

  • Wang XM, Yan JQ, Zhang KM, Mokha SS (1996) Role of opioid receptors (mu, delta 1, delta 2) in modulating responses of nociceptive neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in the rat. Brain Res 739:235–243

    CAS  PubMed  Google Scholar 

  • Wang HB, Zhao B, Zhong YQ, Li KC, Li ZY, Wang Q, Lu YJ, Zhang ZN, He SQ, Zheng HC, Wu SX, Hokfelt TG, Bao L, Zhang X (2010) Coexpression of delta- and mu-opioid receptors in nociceptive sensory neurons. Proc Natl Acad Sci U S A 107:13117–13122

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wei LN, Loh HH (2011) Transcriptional and epigenetic regulation of opioid receptor genes: present and future. Annu Rev Pharmacol Toxicol 51:75–97

    CAS  PubMed  PubMed Central  Google Scholar 

  • Whistler JL, Enquist J, Marley A, Fong J, Gladher F, Tsuruda P, Murray SR, Von Zastrow M (2002) Modulation of postendocytic sorting of G protein-coupled receptors. Science 297:615–620

    CAS  PubMed  Google Scholar 

  • Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC (2012) Structure of the human kappa-opioid receptor in complex with JDTic. Nature 485:327–332

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xie WY, He Y, Yang YR, Li YF, Kang K, Xing BM, Wang Y (2009) Disruption of Cdk5-associated phosphorylation of residue threonine-161 of the delta-opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci 29:3551–3564

    CAS  PubMed  Google Scholar 

  • Yasuda K, Espinosa R 3rd, Takeda J, Le Beau MM, Bell GI (1994) Localization of the kappa opioid receptor gene to human chromosome band 8q11.2. Genomics 19:596–597

    CAS  PubMed  Google Scholar 

  • Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL (2012) Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain 13:524–531

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zaki PA, Bilsky EJ, Vanderah TW, Lai J, Evans CJ, Porreca F (1996) Opioid receptor types and subtypes: the delta receptor as a model. Annu Rev Pharmacol Toxicol 36:379–401

    CAS  PubMed  Google Scholar 

  • Zhang X, Bao L, Arvidsson U, Elde R, Hokfelt T (1998) Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles. Neuroscience 82:1225–1242

    CAS  PubMed  Google Scholar 

  • Zhang X, Bao L, Guan JS (2006) Role of delivery and trafficking of delta-opioid peptide receptors in opioid analgesia and tolerance. Trends Pharmacol Sci 27:324–329

    CAS  PubMed  Google Scholar 

  • Zhang X, Bao L, Ma GQ (2010) Sorting of neuropeptides and neuropeptide receptors into secretory pathways. Prog Neurobiol 90:276–283

    CAS  PubMed  Google Scholar 

  • Zhao B, Wang HB, Lu YJ, Hu JW, Bao L, Zhang X (2011) Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles. Cell Res 21:741–753

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou L, Zhang Q, Stein C, Schafer M (1998) Contribution of opioid receptors on primary afferent versus sympathetic neurons to peripheral opioid analgesia. J Pharmacol Exp Ther 286:1000–1006

    CAS  PubMed  Google Scholar 

  • Zhu Y, Hsu MS, Pintar JE (1998) Developmental expression of the mu, kappa, and delta opioid receptor mRNAs in mouse. J Neurosci 18:2538–2549

    CAS  PubMed  Google Scholar 

  • Zhu Y, King MA, Schuller AG, Nitsche JF, Reidl M, Elde RP, Unterwald E, Pasternak GW, Pintar JE (1999) Retention of supraspinal delta-like analgesia and loss of morphine tolerance in delta opioid receptor knockout mice. Neuron 24:243–252

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada [RGPIN-2015-05213] and the Canadian Institutes of Health Research (CIHR) [MOP 123399] to L.G. L.G. is the recipient of a Chercheur-boursier Senior from the Fonds de la Recherche du Québec-Santé. The authors are grateful to Véronique Blais for her help in editing the manuscript.

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Authors and Affiliations

  1. Département de pharmacologie-physiologie, Université de Sherbrooke, Sherbrooke, QC, Canada

    Khaled Abdallah & Louis Gendron

  2. Institut de pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada

    Khaled Abdallah & Louis Gendron

  3. Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada

    Khaled Abdallah & Louis Gendron

  4. Centre de recherche du CHUS, Sherbrooke, QC, Canada

    Khaled Abdallah & Louis Gendron

  5. Département d’anesthésiologie, Université de Sherbrooke, Sherbrooke, QC, Canada

    Louis Gendron

  6. Quebec Pain Research Network, Sherbrooke, QC, Canada

    Louis Gendron

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  1. Khaled Abdallah
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Correspondence to Louis Gendron .

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  1. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA

    Emily M. Jutkiewicz

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Abdallah, K., Gendron, L. (2017). The Delta Opioid Receptor in Pain Control. In: Jutkiewicz, E. (eds) Delta Opioid Receptor Pharmacology and Therapeutic Applications. Handbook of Experimental Pharmacology, vol 247. Springer, Cham. https://doi.org/10.1007/164_2017_32

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