Abstract
μ-opioid receptor (MOR) agonists such as morphine are powerful analgesics used for pain therapy. However, the use of these drugs is limited by their side-effects, which include antinociceptive tolerance and dependence. Earlier studies reported that MOR analgesic tolerance is reduced by blockade of δ-opioid receptors (DORs) that interact with MORs. Recent studies show that the MOR/DOR interaction in nociceptive afferent neurons in the dorsal root ganglion may contribute to morphine analgesic tolerance. Further analysis of the mechanisms for regulating the trafficking of receptors, ion channels and signaling molecules in nociceptive afferent neurons would help to understand the nociceptive mechanisms and improve pain therapy.
Keywords: peripheral nervous system, opioid receptor, nociceptive pathways
References
- [1].Mennicken F., Zhang J., Hoffert C., Ahmad S., Beaudet A., O’Donnell D. Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia. J Comp Neurol. 2003;465:349–360. doi: 10.1002/cne.10839. [DOI] [PubMed] [Google Scholar]
- [2].Besse D., Lombard M.C., Perrot S., Besson J.M. Regulation of opioid binding sites in the superficial dorsal horn of the rat spinal cord following loose ligation of the sciatic nerve: comparison with sciatic nerve section and lumbar dorsal rhizotomy. Neuroscience. 1992;50:921–933. doi: 10.1016/0306-4522(92)90215-N. [DOI] [PubMed] [Google Scholar]
- [3].Moskowitz A.S., Goodman R.R. Light microscopic autoradiographic localization of μ and δ opioid binding sites in the mouse central nervous system. J Neurosci. 1984;4:1331–1342. doi: 10.1523/JNEUROSCI.04-05-01331.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Gouarderes C., Beaudet A., Zajac J.M., Cros J., Quirion R. High resolution radioautographic localization of [125I]FK-33-824-labelled mu opioid receptors in the spinal cord of normal and deafferented rats. Neuroscience. 1991;43:197–209. doi: 10.1016/0306-4522(91)90427-P. [DOI] [PubMed] [Google Scholar]
- [5].Fields H.L., Emson P.C., Leigh B.K., Gilbert R.F., Iversen L.L. Multiple opiate receptor sites on primary afferent fibres. Nature. 1980;284:351–353. doi: 10.1038/284351a0. [DOI] [PubMed] [Google Scholar]
- [6].Ueda M., Sugimoto K., Oyama T., Kuraishi Y., Satoh M. Opioidergic inhibition of capsaicin-evoked release of glutamate from rat spinal dorsal horn slices. Neuropharmacology. 1995;34:303–308. doi: 10.1016/0028-3908(94)00160-T. [DOI] [PubMed] [Google Scholar]
- [7].Zachariou V., Goldstein B.D. δ-Opioid receptor modulation of the release of substance P-like immunoreactivity in the dorsal horn of the rat following mechanical or thermal noxious stimulation. Brain Res. 1996;736:305–314. doi: 10.1016/0006-8993(96)00718-4. [DOI] [PubMed] [Google Scholar]
- [8].Minami M., Maekawa K., Yabuuchi K., Satoh M. Double in situ hybridization study on coexistence of μ-, δ-, and κ-opioid receptor mRNAs with preprotachykinin A mRNA in the rat dorsal root gang lia. Mol Brain Res. 1995;30:203–210. doi: 10.1016/0169-328X(94)00290-U. [DOI] [PubMed] [Google Scholar]
- [9].Wang H., Wessendorf M.W. Equal proportions of small and large DRG neurons express opioid receptor mRNAs. J Comp Neurol. 2001;429:590–600. doi: 10.1002/1096-9861(20010122)429:4<590::AID-CNE6>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
- [10].Wang H.B., Zhao B., Zhong Y.Q., Li K.C., Li Z.Y., Wang Q., et al. Coexpression of δ- and μ-opioid receptors in nociceptive sensory neurons. Proc Natl Acad Sci U S A. 2010;107:13117–13122. doi: 10.1073/pnas.1008382107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].He S.Q., Zhang Z.N., Guan J.S., Liu H.R., Zhao B., Wang H.B., et al. Facilitation of μ-opioid receptor activity by preventing δ-opioid receptor-mediated codegradation. Neuron. 2011;69:120–131. doi: 10.1016/j.neuron.2010.12.001. [DOI] [PubMed] [Google Scholar]
- [12].Gaveriaux-Ruff C., Nozaki C., Nadal X., Hever X.C., Weibel R., Matifas A., et al. Genetic ablation of delta opioid receptors in nociceptive sensory neurons increases chronic pain and abolishes opioid analgesia. Pain. 2011;152:1238–1248. doi: 10.1016/j.pain.2010.12.031. [DOI] [PubMed] [Google Scholar]
- [13].Standifer K.M., Chien C.C., Wahlestedt C., Brown G.P., Pasternak G.W. Selective loss of delta opioid analgesia and binding by antisense oligodeoxynucleotides to a delta opioid receptor. Neuron. 1994;12:805–810. doi: 10.1016/0896-6273(94)90333-6. [DOI] [PubMed] [Google Scholar]
- [14].Nitsche J.F., Schuller A.G., King M.A., Zengh M., Pasternak G.W., Pintar J.E. Genetic dissociation of opiate tolerance and physical dependence in delta-opioid receptor-1 and preproenkephalin knockout mice. J Neurosci. 2002;22:10906–10913. doi: 10.1523/JNEUROSCI.22-24-10906.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Zhu Y., King M.A., Schuller A.G., Nitsche J.F., Reidl M., Elde R.P., et al. Retention of supraspinal δ-like analgesia and loss of morphine tolerance in δ opioid receptor knockout mice. Neuron. 1999;24:243–252. doi: 10.1016/S0896-6273(00)80836-3. [DOI] [PubMed] [Google Scholar]
- [16].Arvidsson U., Dado R.J., Riedl M., Lee J.H., Law P.Y., Loh H.H., et al. δ-opioid receptor immunoreactivity: distribution in brainstem and spinal cord, and relationship to biogenic amines and enkephalin. J Neurosci. 1995;15:1215–1235. doi: 10.1523/JNEUROSCI.15-02-01215.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Guan J.S., Xu Z.Z., Gao H., He S.Q., Ma G.Q., Sun T., et al. Interaction with vesicle luminal protachykinin regulates surface expression of δ-opioid receptors and opioid analgesia. Cell. 2005;122:619–631. doi: 10.1016/j.cell.2005.06.010. [DOI] [PubMed] [Google Scholar]
- [18].Gupta A., Decaillot F.M., Gomes I., Tkalych O., Heimann A.S., Ferro E.S., et al. Conformation state-sensitive antibodies to G-proteincoupled receptors. J Biol Chem. 2007;282:5116–5124. doi: 10.1074/jbc.M609254200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Gupta A., Rozenfeld R., Gomes I., Raehal K.M., Decaillot F.M., Bohn L.M., et al. Post-activation-mediated changes in opioid receptors detected by N-terminal antibodies. J Biol Chem. 2008;283:10735–10744. doi: 10.1074/jbc.M709454200. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Micovic V., Ivanovic M.D., Dosen-Micovic L. Docking studies suggest ligand-specific delta-opioid receptor conformations. J Mol Model. 2009;15:267–280. doi: 10.1007/s00894-008-0396-7. [DOI] [PubMed] [Google Scholar]
- [21].Petäjä-Repo U.E., Hogue M., Leskelä T.T., Markkanen P.M., Tuusa J.T., Bouvier M. Distinct subcellular localization for constitutive and agonist-modulated palmitoylation of the human δ opioid receptor. J Biol Chem. 2006;281:15780–15789. doi: 10.1074/jbc.M602267200. [DOI] [PubMed] [Google Scholar]
- [22].Scherrer G., Imamachi N., Cao Y.Q., Contet C., Mennicken F., O’Donnell D., et al. Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell. 2009;137:1148–1159. doi: 10.1016/j.cell.2009.04.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [23].Arvidsson U., Riedl M., Chakrabarti S., Lee J.H., Nakano A.H., Dado R.J., et al. Distribution and targeting of a μ opioid receptor (MOR1) in brain and spinal cord. J Neurosci. 1995;15:3328–3341. doi: 10.1523/JNEUROSCI.15-05-03328.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Zhang X., Bao L., Arvidsson U., Elde R., Hökfelt T. 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. 1998;82:1225–1242. doi: 10.1016/S0306-4522(97)00341-2. [DOI] [PubMed] [Google Scholar]
- [25].Zhang X., Bao L., Shi T.J., Ju G., Elde R., Hökfelt T. Down-regulation of mu-opioid receptors in rat and monkey dorsal root ganglion neurons and spinal cord after peripheral axotomy. Neuroscience. 1998;82:223–240. doi: 10.1016/S0306-4522(97)00240-6. [DOI] [PubMed] [Google Scholar]
- [26].Walwyn W., Maidment N.T., Sanders M., Evans C.J., Kieffer B.L., Hales T.G. Induction of δ opioid receptor function by up-regulation of membrane receptors in mouse primary afferent neurons. Mol Pharmacol. 2005;68:1688–1698. doi: 10.1124/mol.105.014829. [DOI] [PubMed] [Google Scholar]
- [27].Rau K.K., Caudle R.M., Cooper B.Y., Johnson R.D. Diverse immunocytochemical expression of opioid receptors in electrophysiologi cally defined cells of rat dorsal root ganglia. J Chem Neuroanatomy. 2005;29:255–264. doi: 10.1016/j.jchemneu.2005.02.002. [DOI] [PubMed] [Google Scholar]
- [28].Wu Z.Z., Chen S.R., Pan H.L. Differential sensitivity of N- and P/Q-type Ca2+ channel currents to a μ opioid in isolectin B4-positive and -negative dorsal root ganglion neurons. J Pharmacol Exp Ther. 2004;311:939–947. doi: 10.1124/jpet.104.073429. [DOI] [PubMed] [Google Scholar]
- [29].Ji R.R., Zhang Q., Law P.Y., Low H.H., Elde R., Hökfelt T. Expression of μ-, δ-, and κ-opioid receptor-like immunoreactivities in rat dorsal root ganglia after carrageenan-induced inflammation. J Neurosci. 1995;15:8156–8166. doi: 10.1523/JNEUROSCI.15-12-08156.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [30].Bao L., Wang H.F., Cai H.J., Tong Y.G., Jin S.X., Lu Y.J., et al. Peripheral axotomy induces only very limited sprouting of coarse myelinated afferents into inner lamina II of rat spinal cord. Eur J Neurosci. 2002;16:175–185. doi: 10.1046/j.1460-9568.2002.02080.x. [DOI] [PubMed] [Google Scholar]
- [31].Joseph E.K., Levine J.D. Mu and delta opioid receptors on nociceptors attenuate mechanical hyperalgesia in rat. Neuroscience. 2010;171:344–350. doi: 10.1016/j.neuroscience.2010.08.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [32].Beaudry H., Dubois D., Gendron L. Activation of spinal μ- and δ-opioid receptors potently inhibits substance P release induced by peripheral noxious stimuli. J Neurosci. 2011;31:13068–13077. doi: 10.1523/JNEUROSCI.1817-11.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33].van Rijn R.M., Brissett D.I., Whistler J.L. Emergence of functional spinal delta opioid receptors after chronic ethanol exposure. Biol Psychiatry. 2012;71:232–238. doi: 10.1016/j.biopsych.2011.07.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [34].Gupta A., Mulder J., Gomes I., Rozenfeld R., Bushlin I., Ong E., et al. Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci Signal. 2010;3:ra54. doi: 10.1126/scisignal.2000807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35].Zhang X., Bao L., Guan J.S. Role of delivery and trafficking of δ-opioid peptide receptors in opioid analgesia and tolerance. Trends Pharmacol Sci. 2006;27:324–329. doi: 10.1016/j.tips.2006.04.005. [DOI] [PubMed] [Google Scholar]
- [36].van Rijn R.M., Whistler J.L., Waldhoer M. Opioid-receptor-heteromerspecific trafficking and pharmacology. Curr Opin Pharmacol. 2010;10:73–79. doi: 10.1016/j.coph.2009.09.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [37].Stockton S.D., Jr, Devi L.A. Functional relevance of μ-δ opioid receptor heteromerization: A Role in novel signaling and implications for the treatment of addiction disorders. Drug Alcohol Depend. 2012;121(3):167–172. doi: 10.1016/j.drugalcdep.2011.10.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [38].Bao L., Jin S.X., Zhang C., Wang L.H., Xu Z.Z., Zhang F.X., et al. Activation of delta opioid receptors induces receptor insertion and neuropeptide secretion. Neuron. 2003;37:121–133. doi: 10.1016/S0896-6273(02)01103-0. [DOI] [PubMed] [Google Scholar]
- [39].Zhao B., Wang H.B., Lu Y.J., Hu J.W., Bao L., Zhang X. Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles. Cell Res. 2011;21:741–753. doi: 10.1038/cr.2011.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [40].Cheng P.Y., Svingos A.L., Wang H., Clarke C.L., Jenab S., Beczkowska I.W., et al. 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. 1995;15:5976–5988. doi: 10.1523/JNEUROSCI.15-09-05976.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [41].Zhang X., Bao L., Ma G.Q. Sorting of neuropeptides and neuropeptide receptors into secretory pathways. Prog Neurobiol. 2010;90:276–283. doi: 10.1016/j.pneurobio.2009.10.011. [DOI] [PubMed] [Google Scholar]
- [42].Ma G.Q., Wang B., Wang H.B., Wang Q., Bao L. Short elements with charged amino acids form clusters to sort protachykinin into large dense-core vesicles. Traffic. 2008;9:2165–2179. doi: 10.1111/j.1600-0854.2008.00836.x. [DOI] [PubMed] [Google Scholar]
- [43].Decaillot F.M., Befort K., Filliol D., Yue S., Walker P., Kieffer B.L. Opioid receptor random mutagenesis reveals a mechanism for G protein-coupled receptor activation. Nat Struct Biol. 2003;10:629–636. doi: 10.1038/nsb950. [DOI] [PubMed] [Google Scholar]
- [44].Meng F., Ueda Y., Hoversten M.T., Thompson R.C., Taylor L., Watson S.J., et al. Mapping the receptor domains critical for the binding selectivity of delta-opioid receptor ligands. Eur J Pharmacol. 1996;311:285–292. doi: 10.1016/0014-2999(96)00431-1. [DOI] [PubMed] [Google Scholar]
- [45].Pepin M.C., Yue S.Y., Roberts E., Wahlestedt C., Walker P. Novel “restoration of function” mutagenesis strategy to identify amino acids of the delta-opioid receptor involved in ligand binding. J Biol Chem. 1997;272:9260–9267. doi: 10.1074/jbc.272.14.9260. [DOI] [PubMed] [Google Scholar]
- [46].Varga E.V., Li X., Stropova D., Zalewska T., Landsman R.S., Knapp R.J., et al. The third extracellular loop of the human delta-opioid receptor determines the selectivity of delta-opioid agonists. Mol Pharmacol. 1996;50:1619–1624. [PubMed] [Google Scholar]
- [47].Wang W.W., Shahrestanifar M., Jin J., Howells R.D. Studies on mu and delta opioid receptor selectivity utilizing chimeric and sitemutagenized receptors. Proc Natl Acad Sci U S A. 1995;92:12436–12440. doi: 10.1073/pnas.92.26.12436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [48].Gendron L., Lucido A.L., Mennicken F., O’Donnell D., Vincent J.P., Stroh T., et al. Morphine and pain-related stimuli enhance cell surface availability of somatic δ-opioid receptors in rat dorsal root ganglia. J Neurosci. 2006;26:953–962. doi: 10.1523/JNEUROSCI.3598-05.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [49].Ma J., Zhang Y., Kalyuzhny A.E., Pan Z.Z. Emergence of functional delta-opioid receptors induced by long-term treatment with morphine. Mol Pharmacol. 2006;69:1137–1145. doi: 10.1124/mol.105.019109. [DOI] [PubMed] [Google Scholar]
- [50].Cahill C.M., Morinville A., Lee M.C., Vincent J.P., Collier B., Beaudet A. Prolonged morphine treatment targets delta opioid receptors to neuronal plasma membranes and enhances delta-mediated antinociception. J Neurosci. 2001;21:7598–7607. doi: 10.1523/JNEUROSCI.21-19-07598.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [51].Patwardhan A.M., Berg K.A., Akopain A.N., Jeske N.A., Gamper N., Clarke W.P., et al. Bradykinin-induced functional competence and trafficking of the δ-opioid receptor in trigeminal nociceptors. J Neurosci. 2005;25:8825–8832. doi: 10.1523/JNEUROSCI.0160-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [52].Scherrer G., Tryoen-Toth P., Filliol D., Matifas A., Laustriat D., Cao Y.Q., et al. Knockin mice expressing fluorescent δ-opioid receptors uncover G protein-coupled receptor dynamics in vivo. Proc Natl Acad Sci U S A. 2006;103:9691–9696. doi: 10.1073/pnas.0603359103. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [53].Li K.C., Zhang F.X., Li C.L., Wang F., Yu M.Y., Zhong Y.Q., et al. Follistatin-like 1 suppresses sensory afferent transmission by activating Na+,K+-ATPase. Neuron. 2011;69:974–987. doi: 10.1016/j.neuron.2011.01.022. [DOI] [PubMed] [Google Scholar]
- [54].Hamada K., Matsuura H., Sanada M., Toyoda F., Omatsu-Kanbe M., Kashiwagi A., et al. Properties of the Na+/K+ pump current in small neurons from adult rat dorsal root ganglia. Br J Pharmacol. 2003;138:1517–1527. doi: 10.1038/sj.bjp.0705170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [55].Mata M., Siegel G.J., Hieber V., Beaty M.W., Fink D.J. Differential distribution of Na,K-ATPase alpha isoform mRNAs in the peripheral nervous system. Brain Res. 1991;546:47–54. doi: 10.1016/0006-8993(91)91157-V. [DOI] [PubMed] [Google Scholar]
- [56].Wu Z.Z., Cai Y.Q., Pan H.L. A functional link between T-type calcium channels and μ-opioid receptor expression in adult primary sensory neurons. J Neurochem. 2009;109:867–878. doi: 10.1111/j.1471-4159.2009.06014.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [57].Deng H., Yang Z., Li Y., Bao G., Friedrich T., Gu Q., et al. Interactions of Na+,K+-ATPase and co-expressed delta-opioid receptor. Neurosci Res. 2009;65:222–227. doi: 10.1016/j.neures.2009.07.003. [DOI] [PubMed] [Google Scholar]
- [58].Heinke B., Gingl E., Sandkuhler J. Multiple targets of μ-opioid receptor-mediated presynaptic inhibition at primary afferent Aδ- and C-fibers. J Neurosci. 2011;31:1313–1322. doi: 10.1523/JNEUROSCI.4060-10.2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [59].Jordan B.A., Trapaidze N., Gomes I., Nivarthi R., Devi L.A. Oligomerization of opioid receptors with β2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci U S A. 2001;98:343–348. doi: 10.1073/pnas.011384898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [60].Jordan B.A., Gomes I., Rios C., Filipovska J., Devi L.A. Functional interactions between μ opioid and α2A-adrenergic receptors. Mol Pharmacol. 2003;64:1317–1324. doi: 10.1124/mol.64.6.1317. [DOI] [PubMed] [Google Scholar]
- [61].Overland A.C., Kitto K.F., Chabot-Dore A.J., Rothwell P.E., Fairbanks C.A., Stone L.S., et al. Protein kinase C mediates the synergistic interaction between agonists acting at α2-adrenergic and delta-opioid receptors in spinal cord. J Neurosci. 2009;29:13264–13273. doi: 10.1523/JNEUROSCI.1907-09.2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [62].Petäjä-Repo U.E., Hogue M., Bhalla S., Laperriere A., Morello J.P., Bouvier M. Ligands act as pharmacological chaperones and increase the efficiency of delta opioid receptor maturation. EMBO J. 2002;21:1628–1637. doi: 10.1093/emboj/21.7.1628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [63].Bie B., Zhang Z., Cai Y.Q., Zhu W., Zhang Y., Dai J., et al. Nerve growth factor-regulated emergence of functional δ-opioid receptors. J Neurosci. 2010;30:5617–5628. doi: 10.1523/JNEUROSCI.5296-09.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [64].Margolis E.B., Mitchell J.M., Hjelmstad G.O., Fields H.L. A novel δ opioid receptor-mediated enhancement of GABAA receptor function induced by stress in ventral tegmental area neurons. J Physiol. 2011;589:4229–4242. doi: 10.1113/jphysiol.2011.209023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [65].Milan-Lobo L., Whistler J.L. Heteromerization of the μ- and δ-opioid receptors produces ligand-biased antagonism and alters μ-receptor trafficking. J Pharmacol Exp Ther. 2011;337:868–875. doi: 10.1124/jpet.111.179093. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [66].Cesselin F., Bourgoin S., Clot A.M., Hamon M., Le Bars D. Segmental release of Met-enkephalin-like material from the spinal cord of rats, elicited by noxious thermal stimuli. Brain Res. 1989;484:71–77. doi: 10.1016/0006-8993(89)90349-1. [DOI] [PubMed] [Google Scholar]
- [67].Cheng Z.J., Yu Q.M., Wu Y.L., Ma L., Pei G. Selective interference of β-arrestin 1 with κ and δ but not μ opioid receptor/G protein coupling. J Biol Chem. 1998;273:24328–24333. doi: 10.1074/jbc.273.38.24328. [DOI] [PubMed] [Google Scholar]
- [68].Rozenfeld R., Devi L.A. Receptor heterodimerization leads to a switch in signaling: β-arrestin2-mediated ERK activation by μ-δ opioid receptor heterodimers. FASEB J. 2007;21:2455–2465. doi: 10.1096/fj.06-7793com. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [69].Chao D., Xia Y. Ionic storm in hypoxic/ischemic stress: can opioid receptors subside it? Prog Neurobiol. 2010;90:439–470. doi: 10.1016/j.pneurobio.2009.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [70].Pradhan A.A., Befort K., Nozaki C., Gaveriaux-Ruff C., Kieffer B.L. The delta opioid receptor: an evolving target for the treatment of brain disorders. Trends Pharmacol Sci. 2011;32:581–590. doi: 10.1016/j.tips.2011.06.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [71].Berger A.C., Whistler J.L. How to design an opioid drug that causes reduced tolerance and dependence. Ann Neurol. 2010;67:559–569. doi: 10.1002/ana.22002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [72].Kim H.J., Seol T.K., Lee H.J., Yaksh T.L., Jun J.H. The effect of intrathecal mu, delta, kappa, and alpha-2 agonists on thermal hyperalgesia induced by mild burn on hind paw in rats. J Anesth. 2011;25:884–891. doi: 10.1007/s00540-011-1240-2. [DOI] [PubMed] [Google Scholar]
- [73].Janecka A., Fichna J., Janecki T. Opioid receptors and their ligands. Curr Top Med Chem. 2004;4:1–17. doi: 10.2174/1568026043451618. [DOI] [PubMed] [Google Scholar]
- [74].Trescot A.M., Datta S., Lee M., Hansen H. Opioid pharmacology. Pain Physician. 2008;11:S133–153. [PubMed] [Google Scholar]
- [75].Matthes H.W., Smadja C., Valverde O., Vonesch J.L., Foutz A.S., Boudinot E., et al. Activity of the δ-opioid receptor is partially reduced, whereas activity of the κ-receptor is maintained in mice lacking the μ-receptor. J Neurosci. 1998;18:7285–7295. doi: 10.1523/JNEUROSCI.18-18-07285.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [76].Scherrer G., Befort K., Contet C., Becker J., Matifas A., Kieffer B.L. The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: a parallel study of mu, delta and combinatorial opioid receptor knockout mice. Eur J Neurosci. 2004;19:2239–2248. doi: 10.1111/j.0953-816X.2004.03339.x. [DOI] [PubMed] [Google Scholar]
- [77].van Rijn R.M., Whistler J.L. The δ1 opioid receptor is a heterodimer that opposes the actions of the δ2 receptor on alcohol intake. Biol Psychiatry. 2009;66:777–784. doi: 10.1016/j.biopsych.2009.05.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [78].Dubois D., Gendron L. Delta opioid receptor-mediated analgesia is not altered in preprotachykinin A knockout mice. Eur J Neurosci. 2010;32:1921–1929. doi: 10.1111/j.1460-9568.2010.07466.x. [DOI] [PubMed] [Google Scholar]
- [79].Wrigley P.J., Jeong H.J., Vaughan C.W. Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn. Mol Pain. 2010;6:71. doi: 10.1186/1744-8069-6-71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [80].Manchikanti L., Singh A. Therapeutic opioids: a ten-year perspective on the complexities and complications of the escalating use, abuse, and nonmedical use of opioids. Pain Physician. 2008;11:S63–88. [PubMed] [Google Scholar]
- [81].Fields H.L. The doctor’s dilemma: opiate analgesics and chronic pain. Neuron. 2011;69:591–594. doi: 10.1016/j.neuron.2011.02.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [82].Fields H. State-dependent opioid control of pain. Nat Rev Neurosci. 2004;5:565–575. doi: 10.1038/nrn1431. [DOI] [PubMed] [Google Scholar]
- [83].Abdelhamid E.E., Sultana M., Portoghese P.S., Takemori A.E. Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice. J Pharmacol Exp Ther. 1991;258:299–303. [PubMed] [Google Scholar]
- [84].Schiller P.W. Bi- or multifunctional opioid peptide drugs. Life Sci. 2010;86:598–603. doi: 10.1016/j.lfs.2009.02.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [85].Schiller P.W., Fundytus M.E., Merovitz L., Weltrowska G., Nguyen T.M., Lemieux C., et al. The opioid μ agonist/δ antagonist DIPPNH2[ψ] produces a potent analgesic effect, no physical dependence, and less tolerance than morphine in rats. J Med Chem. 1999;42:3520–3526. doi: 10.1021/jm980724+. [DOI] [PubMed] [Google Scholar]
- [86].Schiller P.W., Weltrowska G., Berezowska I., Nguyen T.M., Wilkes B.C., Lemieux C., et al. The TIPP opioid peptide family: development of δ antagonists, δ agonists, and mixed μ agonist/δ antagonists. Biopolymers. 1999;51:411–425. doi: 10.1002/(SICI)1097-0282(1999)51:6<411::AID-BIP4>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
- [87].George S.R., Fan T., Xie Z., Tse R., Tam V., Varghese G., et al. Oligomerization of μ- and δ-opioid receptors. Generation of novel functional properties. J Biol Chem. 2000;275:26128–26135. doi: 10.1074/jbc.M000345200. [DOI] [PubMed] [Google Scholar]
- [88].Jordan B.A., Devi L.A. G-protein-coupled receptor heterodimerization modulates receptor function. Nature. 1999;399:697–700. doi: 10.1038/21441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [89].Law P.Y., Erickson-Herbrandson L.J., Zha Q.Q., Solberg J., Chu J., Sarre A., et al. Heterodimerization of μ- and δ-opioid receptors occurs at the cell surface only and requires receptor-G protein interactions. J Biol Chem. 2005;280:11152–11164. doi: 10.1074/jbc.M500171200. [DOI] [PubMed] [Google Scholar]
- [90].Gomes I., Gupta A., Filipovska J., Szeto H.H., Pintar J.E., Devi L.A. A role for heterodimerization of μ and δ opiate receptors in enhancing morphine analgesia. Proc Natl Acad Sci U S A. 2004;101:5135–5139. doi: 10.1073/pnas.0307601101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [91].Xie W.Y., He Y., Yang Y.R., Li Y.F., Kang K., Xing B.M., et al. Disruption of Cdk5-associated phosphorylation of residue threonine-161 of the δ-opioid receptor: impaired receptor function and attenuated morphine antinociceptive tolerance. J Neurosci. 2009;29:3551–3564. doi: 10.1523/JNEUROSCI.0415-09.2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [92].Minneman K.P. Heterodimerization and surface localization of G protein coupled receptors. Biochem Pharmacol. 2007;73:1043–1050. doi: 10.1016/j.bcp.2006.09.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [93].He L., Fong J., von Zastrow M., Whistler J.L. Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization. Cell. 2002;108:271–282. doi: 10.1016/S0092-8674(02)00613-X. [DOI] [PubMed] [Google Scholar]
- [94].Yu Y.J., Dhavan R., Chevalier M.W., Yudowski G.A., von Zastrow M. Rapid delivery of internalized signaling receptors to the somatodendritic surface by sequence-specific local insertion. J Neurosci. 2010;30:11703–11714. doi: 10.1523/JNEUROSCI.6282-09.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [95].Puthenveedu M.A., Lauffer B., Temkin P., Vistein R., Carlton P., Thorn K., et al. Sequence-dependent sorting of recycling proteins by actinstabilized endosomal microdomains. Cell. 2010;143:761–773. doi: 10.1016/j.cell.2010.10.003. [DOI] [PMC free article] [PubMed] [Google Scholar]