4,013
Views
42
CrossRef citations to date
0
Altmetric
Review

The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence

, , , , , & show all
Pages 235-243 | Received 02 Mar 2015, Accepted 30 Jun 2015, Published online: 01 Sep 2015

Reference

  • Gamse R, Holzer P, Lembeck F. Indirect evidence for presynaptic location of opiate receptors on chemosensitive primary sensory neurones. Naunyn-Schmiedeberg's Arch Pharmacol 1979; 308:281-5; PMID:228212; http://dx.doi.org/10.1007/BF00501394
  • Yoshimura M, North RA. Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature 1983; 305:529-30; PMID:6621700; http://dx.doi.org/10.1038/305529a0
  • Yaksh TL, Noueihed R. The physiology and pharmacology of spinal opiates. Ann Rev Pharmacol Toxicol 1985; 25:433-62; PMID:2988422; http://dx.doi.org/10.1146/annurev.pa.25.040185.002245
  • Chen SR, Pan HL. Blocking mu opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids. Brain Res 2006; 1081:119-25; PMID:16499888; http://dx.doi.org/10.1016/j.brainres.2006.01.053
  • Hutchinson MR, Coats BD, Lewis SS, Zhang Y, Sprunger DB, Rezvani N, Baker EM, Jekich BM, Wieseler JL, Somogyi AA, et al. Proinflammatory cytokines oppose opioid-induced acute and chronic analgesia. Brain Behav Immun 2008; 22:1178-89; PMID:18599265; http://dx.doi.org/10.1016/j.bbi.2008.05.004
  • King T, Gardell LR, Wang R, Vardanyan A, Ossipov MH, Malan TP, Jr., Vanderah TW, Hunt SP, Hruby VJ, Lai J, et al. Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain 2005; 116:276-88; PMID:15964684; http://dx.doi.org/10.1016/j.pain.2005.04.014
  • Yue X, Tumati S, Navratilova E, Strop D, St John PA, Vanderah TW, Roeske WR, Yamamura HI, Varga EV. Sustained morphine treatment augments basal CGRP release from cultured primary sensory neurons in a Raf-1 dependent manner. Eur J Pharmacol 2008; 584:272-7; PMID:18328477; http://dx.doi.org/10.1016/j.ejphar.2008.02.013
  • Powell KJ, Ma W, Sutak M, Doods H, Quirion R, Jhamandas K. Blockade and reversal of spinal morphine tolerance by peptide and non-peptide calcitonin gene-related peptide receptor antagonists. Br J Pharmacol 2000; 131:875-84; PMID:11053206; http://dx.doi.org/10.1038/sj.bjp.0703655
  • Ossipov MH, Lai J, King T, Vanderah TW, Malan TP, Jr., Hruby VJ, Porreca F. Antinociceptive and nociceptive actions of opioids. J Neurobiol 2004; 61:126-48; PMID:15362157; http://dx.doi.org/10.1002/neu.20091
  • Vardanyan A, Wang R, Vanderah TW, Ossipov MH, Lai J, Porreca F, King T. TRPV1 receptor in expression of opioid-induced hyperalgesia. J Pain 2009; 10:243-52; PMID:18774343; http://dx.doi.org/10.1016/j.jpain.2008.07.004
  • Por ED, Bierbower SM, Berg KA, Gomez R, Akopian AN, Wetsel WC, Jeske NA. beta-Arrestin-2 desensitizes the transient receptor potential vanilloid 1 (TRPV1) channel. J Biol Chem 2012; 287:37552-63; PMID:22952227; http://dx.doi.org/10.1074/jbc.M112.391847
  • Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 1997; 389:816-24; PMID:9349813; http://dx.doi.org/10.1038/39807
  • Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 1998; 21:531-43; PMID:9768840; http://dx.doi.org/10.1016/S0896-6273(00)80564-4
  • Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000; 288:306-13; PMID:10764638; http://dx.doi.org/10.1126/science.288.5464.306
  • Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sorgard M, Di Marzo V, Julius D, Högestätt ED. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 1999; 400:452-7; PMID:10440374; http://dx.doi.org/10.1038/22761
  • Szallasi A, Nilsson S, Farkas-Szallasi T, Blumberg PM, Hokfelt T, Lundberg JM. Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment. Brain Res 1995; 703:175-83; PMID:8719630; http://dx.doi.org/10.1016/0006-8993(95)01094-7
  • Tominaga M, Julius D. Capsaicin receptor in the pain pathway. Jpn J Pharmacol 2000; 83:20-4; PMID:10887936; http://dx.doi.org/10.1254/jjp.83.20
  • Szallasi A, Cruz F, Geppetti P. TRPV1: a therapeutic target for novel analgesic drugs? Trends Mol Med 2006; 12:545-54; PMID:16996800; http://dx.doi.org/10.1016/j.molmed.2006.09.001
  • Levine JD, Alessandri-Haber N. TRP channels: targets for the relief of pain. Biochimica et biophysica acta 2007; 1772:989-1003; PMID:17321113; http://dx.doi.org/10.1016/j.bbadis.2007.01.008
  • Roberts JC, Davis JB, Benham CD.; 3HResiniferatoxin autoradiography in the CNS of wild-type and TRPV1 null mice defines TRPV1 (VR-1) protein distribution. Brain Res 2004; 995:176-83; PMID:14672807; http://dx.doi.org/10.1016/j.brainres.2003.10.001
  • Chen Y, Geis C, Sommer C. Activation of TRPV1 contributes to morphine tolerance: involvement of the mitogen-activated protein kinase signaling pathway. J Neurosci 2008; 28:5836-45; PMID:18509045; http://dx.doi.org/10.1523/JNEUROSCI.4170-07.2008
  • Niiyama Y, Kawamata T, Yamamoto J, Omote K, Namiki A. Bone cancer increases transient receptor potential vanilloid subfamily 1 expression within distinct subpopulations of dorsal root ganglion neurons. Neuroscience 2007; 148:560-72; PMID:17656027; http://dx.doi.org/10.1016/j.neuroscience.2007.05.049
  • Chen SR, Pan HL. Loss of TRPV1-expressing sensory neurons reduces spinal mu opioid receptors but paradoxically potentiates opioid analgesia. J Neurophysiol 2006; 95:3086-96; PMID:16467418; http://dx.doi.org/10.1152/jn.01343.2005
  • Nguyen TL, Nam YS, Lee SY, Kim HC, Jang CG. Effects of capsazepine, a transient receptor potential vanilloid type 1 antagonist, on morphine-induced antinociception, tolerance, and dependence in mice. Br J Anaesth 2010; 105:668-74; PMID:20719804; http://dx.doi.org/10.1093/bja/aeq212
  • Akins PT, McCleskey EW. Characterization of potassium currents in adult rat sensory neurons and modulation by opioids and cyclic AMP. Neuroscience 1993; 56:759-69; PMID:8255432; http://dx.doi.org/10.1016/0306-4522(93)90372-M
  • Borgland SL, Connor M, Christie MJ. Nociceptin inhibits calcium channel currents in a subpopulation of small nociceptive trigeminal ganglion neurons in mouse. J Physiol 2001; 536:35-47; PMID:11579155; http://dx.doi.org/10.1111/j.1469-7793.2001.t01-1-00035.x
  • Irnaten M, Aicher SA, Wang J, Venkatesan P, Evans C, Baxi S, Mendelowitz D. Mu-opioid receptors are located postsynaptically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neurons in the rat nucleus ambiguus. Neuroscience 2003; 116:573-82; PMID:12559112; http://dx.doi.org/10.1016/S0306-4522(02)00657-7
  • Law PY, Wong YH, Loh HH. Molecular mechanisms and regulation of opioid receptor signaling. Ann Rev Pharmacol Toxicol 2000; 40:389-430; PMID:10836142; http://dx.doi.org/10.1146/annurev.pharmtox.40.1.389
  • Spahn V, Fischer O, Endres-Becker J, Schafer M, Stein C, Zollner C. Opioid withdrawal increases transient receptor potential vanilloid 1 activity in a protein kinase A-dependent manner. Pain 2013; 154:598-608; PMID:23398938; http://dx.doi.org/10.1016/j.pain.2012.12.026
  • Rowan MP, Bierbower SM, Eskander MA, Szteyn K, Por ED, Gomez R, Veldhuis N, Bunnett NW, Jeske NA. Activation of mu opioid receptors sensitizes transient receptor potential vanilloid type 1 (TRPV1) via beta-arrestin-2-mediated cross-talk. PloS one 2014; 9:e93688; PMID:24695785; http://dx.doi.org/10.1371/journal.pone.0093688
  • Sasamura T, Sasaki M, Tohda C, Kuraishi Y. Existence of capsaicin-sensitive glutamatergic terminals in rat hypothalamus. Neuroreport 1998; 9:2045-8; PMID:9674591; http://dx.doi.org/10.1097/00001756-199806220-00025
  • Koulchitsky SV, Azev OA, Gourine AV, Kulchitsky VA. Capsaicin-sensitive area in the ventral surface of the rat medulla. Neurosci Lett 1994; 182:129-32; PMID:7536311; http://dx.doi.org/10.1016/0304-3940(94)90780-3
  • Bhave G, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RWF. cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation. Neuron 2002; 35:721-31; PMID:12194871; http://dx.doi.org/10.1016/S0896-6273(02)00802-4
  • Bhave G, Hu HJ, Glauner KS, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW 4th. Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Proc Natl Acad Sci U S A 2003; 100:12480-5; PMID:14523239; http://dx.doi.org/10.1073/pnas.2032100100
  • Jung J, Shin JS, Lee SY, Hwang SW, Koo J, Cho H, Oh U. Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding. J Biol Chem 2004; 279:7048-54; PMID:14630912; http://dx.doi.org/10.1074/jbc.M311448200
  • Koplas PA, Rosenberg RL, Oxford GS. The role of calcium in the desensitization of capsaicin responses in rat dorsal root ganglion neurons. J Neurosci 1997; 17:3525-37; PMID:9133377
  • Mohapatra DP, Nau C. Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. J Biol Chem 2005; 280:13424-32; PMID:15691846; http://dx.doi.org/10.1074/jbc.M410917200
  • Ma W, Quirion R. The ERK/MAPK pathway, as a target for the treatment of neuropathic pain. Exp Opin ther Targets 2005; 9:699-713; PMID:16083338; http://dx.doi.org/10.1517/14728222.9.4.699
  • Tohda C, Sasaki M, Konemura T, Sasamura T, Itoh M, Kuraishi Y. Axonal transport of VR1 capsaicin receptor mRNA in primary afferents and its participation in inflammation-induced increase in capsaicin sensitivity. J Neurochem 2001; 76:1628-35; PMID:11259480; http://dx.doi.org/10.1046/j.1471-4159.2001.00193.x
  • Amaya F, Oh-hashi K, Naruse Y, Iijima N, Ueda M, Shimosato G, Tominaga M, Tanaka Y, Tanaka M. Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res 2003; 963:190-6; PMID:12560124; http://dx.doi.org/10.1016/S0006-8993(02)03972-0
  • Pomonis JD, Harrison JE, Mark L, Bristol DR, Valenzano KJ, Walker K. N-(4-Tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyrazine -1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: II. in vivo characterization in rat models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 2003; 306:387-93; PMID:12721336; http://dx.doi.org/10.1124/jpet.102.046268
  • Jancso G, Jancso-Gabor A. Effect of capsaicin on morphine analgesia-possible involvement of hypothalamic structures. Naunyn-Schmiedeberg's Arch pharmacol 1980; 311:285-8; PMID:7393343; http://dx.doi.org/10.1007/BF00569408
  • Bevan S, Szolcsanyi J. Sensory neuron-specific actions of capsaicin: mechanisms and applications. Trends Pharmacol Sci 1990; 11:330-3; PMID:2203194; http://dx.doi.org/10.1016/0165-6147(90)90237-3
  • Ko MC, Johnson MD, Butelman ER, Willmont KJ, Mosberg HI, Woods JH. Intracisternal nor-binaltorphimine distinguishes central and peripheral kappa-opioid antinociception in rhesus monkeys. J Pharmacol Exp Ther 1999; 291:1113-20; PMID:10565831
  • Caterina MJ, Julius D. The vanilloid receptor: a molecular gateway to the pain pathway. Ann Rev Neurosci 2001; 24:487-517; PMID:11283319; http://dx.doi.org/10.1146/annurev.neuro.24.1.487
  • Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002; 36:57-68; PMID:12367506; http://dx.doi.org/10.1016/S0896-6273(02)00908-X
  • Amaya F, Shimosato G, Nagano M, Ueda M, Hashimoto S, Tanaka Y, Suzuki H, Tanaka M. NGF and GDNF differentially regulate TRPV1 expression that contributes to development of inflammatory thermal hyperalgesia. Eur J Neurosci 2004; 20:2303-10; PMID:15525272; http://dx.doi.org/10.1111/j.1460-9568.2004.03701.x
  • Breese NM, George AC, Pauers LE, Stucky CL. Peripheral inflammation selectively increases TRPV1 function in IB4-positive sensory neurons from adult mouse. Pain 2005; 115:37-49; PMID:15836968; http://dx.doi.org/10.1016/j.pain.2005.02.010
  • Endres-Becker J, Heppenstall PA, Mousa SA, Labuz D, Oksche A, Schafer M, Stein C, Zöllner C. Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Mol Pharmacol 2007; 71:12-8; PMID:17005903; http://dx.doi.org/10.1124/mol.106.026740
  • Walker KM, Urban L, Medhurst SJ, Patel S, Panesar M, Fox AJ, McIntyre P. The VR1 antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain. J Pharmacol Exp Ther 2003; 304:56-62; PMID:12490575; http://dx.doi.org/10.1124/jpet.102.042010
  • Fields HL, Emson PC, Leigh BK, Gilbert RF, Iversen LL. Multiple opiate receptor sites on primary afferent fibres. Nature 1980; 284:351-3; PMID:6244504; http://dx.doi.org/10.1038/284351a0
  • Kohno T, Kumamoto E, Higashi H, Shimoji K, Yoshimura M. Actions of opioids on excitatory and inhibitory transmission in substantia gelatinosa of adult rat spinal cord. J Physiol 1999; 518 (Pt 3):803-13; PMID:10420016; http://dx.doi.org/10.1111/j.1469-7793.1999.0803p.x
  • Abbadie C, Lombard MC, Besson JM, Trafton JA, Basbaum AI. Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin: an analysis of pre- and postsynaptic receptor distributions. Brain Res 2002; 930:150-62; PMID:11879805; http://dx.doi.org/10.1016/S0006-8993(02)02242-4
  • Light AR, Willcockson HH. Spinal laminae I-II neurons in rat recorded in vivo in whole cell, tight seal configuration: properties and opioid responses. Journal of Neurophysiol 1999; 82:3316-26; PMID:10601463
  • Marker CL, Lujan R, Colon J, Wickman K. Distinct populations of spinal cord lamina II interneurons expressing G-protein-gated potassium channels. J Neurosci 2006; 26:12251-9; PMID:17122050; http://dx.doi.org/10.1523/JNEUROSCI.3693-06.2006
  • Magnuson DS, Dickenson AH. Lamina-specific effects of morphine and naloxone in dorsal horn of rat spinal cord in vitro. J Neurophysiol 1991; 66:1941-50; PMID:1812227
  • Stein C, Schafer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med 2003; 9:1003-8; PMID:12894165; http://dx.doi.org/10.1038/nm908
  • Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, et al. TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonists. J Neurosci 2006; 26:9385-93; PMID:16971522; http://dx.doi.org/10.1523/JNEUROSCI.1246-06.2006
  • Chen SR, Prunean A, Pan HM, Welker KL, Pan HL. Resistance to morphine analgesic tolerance in rats with deleted transient receptor potential vanilloid type 1-expressing sensory neurons. Neuroscience 2007; 145:676-85; PMID:17239544; http://dx.doi.org/10.1016/j.neuroscience.2006.12.016
  • Zhou HY, Chen SR, Chen H, Pan HL. Sustained inhibition of neurotransmitter release from nontransient receptor potential vanilloid type 1-expressing primary afferents by mu-opioid receptor activation-enkephalin in the spinal cord. J Pharmacol Exp Ther 2008; 327:375-82; PMID:18669865; http://dx.doi.org/10.1124/jpet.108.141226
  • Jeske NA, Diogenes A, Ruparel NB, Fehrenbacher JC, Henry M, Akopian AN, Hargreaves KM. A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1. Pain 2008; 138:604-16; PMID:18381233; http://dx.doi.org/10.1016/j.pain.2008.02.022
  • Schnizler K, Shutov LP, Van Kanegan MJ, Merrill MA, Nichols B, McKnight GS, Strack S, Hell JW, Usachev YM. Protein kinase A anchoring via AKAP150 is essential for TRPV1 modulation by forskolin and prostaglandin E2 in mouse sensory neurons. J Neurosci 2008; 28:4904-17; PMID:18463244; http://dx.doi.org/10.1523/JNEUROSCI.0233-08.2008
  • Zhang X, Li L, McNaughton PA. Proinflammatory mediators modulate the heat-activated ion channel TRPV1 via the scaffolding protein AKAP79/150. Neuron 2008; 59:450-61; PMID:18701070; http://dx.doi.org/10.1016/j.neuron.2008.05.015
  • Jeske NA, Patwardhan AM, Ruparel NB, Akopian AN, Shapiro MS, Henry MA. A-kinase anchoring protein 150 controls protein kinase C-mediated phosphorylation and sensitization of TRPV1. Pain 2009; 146:301-7; PMID:19767149; http://dx.doi.org/10.1016/j.pain.2009.08.002
  • Faux MC, Scott JD. Molecular glue: kinase anchoring and scaffold proteins. Cell 1996; 85:9-12; PMID:8620541; http://dx.doi.org/10.1016/S0092-8674(00)81075-2
  • Pawson T, Scott JD. Signaling through scaffold, anchoring, and adaptor proteins. Science 1997; 278:2075-80; PMID:9405336; http://dx.doi.org/10.1126/science.278.5346.2075
  • DeFea KA. Beta-arrestins as regulators of signal termination and transduction: how do they determine what to scaffold? Cell Signal 2011; 23:621-9; PMID:20946952; http://dx.doi.org/10.1016/j.cellsig.2010.10.004
  • Houslay MD, Baillie GS. Beta-arrestin-recruited phosphodiesterase-4 desensitizes the AKAP79/PKA-mediated switching of beta2-adrenoceptor signalling to activation of ERK. Biochem Soc Trans 2005; 33:1333-6; PMID:16246112; http://dx.doi.org/10.1042/BST20051333
  • Dasgupta P, Rastogi S, Pillai S, Ordonez-Ercan D, Morris M, Haura E, Chellappan S. Nicotine induces cell proliferation by beta-arrestin-mediated activation of Src and Rb-Raf-1 pathways. J Clin Investig 2006; 116:2208-17; PMID:16862215; http://dx.doi.org/10.1172/JCI28164
  • Xiao K, McClatchy DB, Shukla AK, Zhao Y, Chen M, Shenoy SK, Yates JR 3rd, Lefkowitz RJ. Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proc Natl Acad Sci U S A 2007; 104:12011-6; PMID:17620599; http://dx.doi.org/10.1073/pnas.0704849104
  • Li X, Baillie GS, Houslay MD. Mdm2 directs the ubiquitination of beta-arrestin-sequestered cAMP phosphodiesterase-4D5. J Biol Chem 2009; 284:16170-82; PMID:19372219; http://dx.doi.org/10.1074/jbc.M109.008078
  • Perry SJ, Baillie GS, Kohout TA, McPhee I, Magiera MM, Ang KL, Miller WE, McLean AJ, Conti M, Houslay MD, et al. Targeting of cyclic AMP degradation to beta 2-adrenergic receptors by beta-arrestins. Science 2002; 298:834-6; PMID:12399592; http://dx.doi.org/10.1126/science.1074683
  • Baillie GS, Sood A, McPhee I, Gall I, Perry SJ, Lefkowitz RJ, Houslay MD. beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. Proc Natl Acad Sci U S A 2003; 100:940-5; PMID:12552097; http://dx.doi.org/10.1073/pnas.262787199
  • Daaka Y, Luttrell LM, Ahn S, Della Rocca GJ, Ferguson SS, Caron MG, Lefkowitz RJ. Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase. J Biol Chem 1998; 273:685-8; PMID:9422717; http://dx.doi.org/10.1074/jbc.273.2.685
  • Vogler O, Nolte B, Voss M, Schmidt M, Jakobs KH, van Koppen CJ. Regulation of muscarinic acetylcholine receptor sequestration and function by beta-arrestin. J Biol Chem 1999; 274:12333-8; PMID:10212203; http://dx.doi.org/10.1074/jbc.274.18.12333
  • Reiter E, Lefkowitz RJ. GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling. Trends Endocrinol Metab 2006; 17:159-65; PMID:16595179; http://dx.doi.org/10.1016/j.tem.2006.03.008
  • Lefkowitz RJ, Rajagopal K, Whalen EJ. New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors. Mol Cell 2006; 24:643-52; PMID:17157248; http://dx.doi.org/10.1016/j.molcel.2006.11.007
  • Kovacs JJ, Hara MR, Davenport CL, Kim J, Lefkowitz RJ. Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways. Dev Cell 2009; 17:443-58; PMID:19853559; http://dx.doi.org/10.1016/j.devcel.2009.09.011
  • Shukla AK, Kim J, Ahn S, Xiao K, Shenoy SK, Liedtke W, Lefkowitz RJ. Arresting a transient receptor potential (TRP) channel: beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4. J Biol Chem 2010; 285:30115-25; PMID:20650893; http://dx.doi.org/10.1074/jbc.M110.141549
  • Bohn LM, Lefkowitz RJ, Caron MG. Differential mechanisms of morphine antinociceptive tolerance revealed in (beta)arrestin-2 knock-out mice. J Neurosci 2002; 22:10494-500; PMID:12451149
  • Raehal KM, Bohn LM. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology 2011; 60:58-65; PMID:20713067; http://dx.doi.org/10.1016/j.neuropharm.2010.08.003
  • Bohn LM, Lefkowitz RJ, Gainetdinov RR, Peppel K, Caron MG, Lin FT. Enhanced morphine analgesia in mice lacking beta-arrestin 2. Science 1999; 286:2495-8; PMID:10617462; http://dx.doi.org/10.1126/science.286.5449.2495
  • Gavalas A, Victoratos P, Yiangou M, Hadjipetrou-Kourounakis L, Rekka E, Kourounakis P. The anti-inflammatory effect of opioids. Int J Neurosci 1994; 74:259-64; PMID:7928110; http://dx.doi.org/10.3109/00207459408987244
  • Hong Y, Abbott FV. Peripheral opioid modulation of pain and inflammation in the formalin test. Eur J Pharmacol 1995; 277:21-8; PMID:7635169; http://dx.doi.org/10.1016/0014-2999(95)00045-M
  • Stein A, Yassouridis A, Szopko C, Helmke K, Stein C. Intraarticular morphine versus dexamethasone in chronic arthritis. Pain 1999; 83:525-32; PMID:10568861; http://dx.doi.org/10.1016/S0304-3959(99)00156-6
  • Stein C, Machelska H, Schafer M. Peripheral analgesic and antiinflammatory effects of opioids. Zeitschrift fur Rheumatologie 2001; 60:416-24; PMID:11826735; http://dx.doi.org/10.1007/s003930170004
  • Ko MC, Tuchman JE, Johnson MD, Wiesenauer K, Woods JH. Local administration of mu or kappa opioid agonists attenuates capsaicin-induced thermal hyperalgesia via peripheral opioid receptors in rats. Psychopharmacology 2000; 148:180-5; PMID:10663433; http://dx.doi.org/10.1007/s002130050040
  • Barrett AC, Smith ES, Picker MJ. Capsaicin-induced hyperalgesia and mu-opioid-induced antihyperalgesia in male and female Fischer 344 rats. J Pharmacol Exp Ther 2003; 307:237-45; PMID:12954802; http://dx.doi.org/10.1124/jpet.103.054478
  • Wenk HN, Nannenga MN, Honda CN. Effect of morphine sulphate eye drops on hyperalgesia in the rat cornea. Pain 2003; 105:455-65; PMID:14527706; http://dx.doi.org/10.1016/S0304-3959(03)00260-4
  • 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; 72:3092-6; PMID:1059094; http://dx.doi.org/10.1073/pnas.72.8.3092
  • Mohapatra DP, Nau C. Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway. J Biol Chem 2003; 278:50080-90; PMID:14506258; http://dx.doi.org/10.1074/jbc.M306619200
  • Vetter I, Cheng W, Peiris M, Wyse BD, Roberts-Thomson SJ, Zheng J, Monteith GR, Cabot PJ. Rapid, opioid-sensitive mechanisms involved in transient receptor potential vanilloid 1 sensitization. J Biol Chem 2008; 283:19540-50; PMID:18482991; http://dx.doi.org/10.1074/jbc.M707865200
  • Vetter I, Wyse BD, Monteith GR, Roberts-Thomson SJ, Cabot PJ. The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway. Mol Pain 2006; 2:22; PMID:16842630; http://dx.doi.org/10.1186/1744-8069-2-22
  • Bao Y, Gao Y, Yang L, Kong X, Zheng H, Hou W, Hua B. New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review. Channels 2015; 9:5-13; PMID:25664811; http://dx.doi.org/10.4161/19336950.2014.995001
  • Hua B, Gao Y, Kong X, Yang L, Hou W, Bao Y. New insights of nociceptor sensitization in bone cancer pain. Exp Opin Ther Targets 2015; 19:227-43; PMID:25547644; http://dx.doi.org/10.1517/14728222.2014.980815
  • Lopshire JC, Nicol GD. The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and single-channel studies. J Neurosci 1998; 18:6081-92; PMID:9698303
  • De Petrocellis L, Harrison S, Bisogno T, Tognetto M, Brandi I, Smith GD, Creminon C, Davis JB, Geppetti P, Di Marzo V. The vanilloid receptor (VR1)-mediated effects of anandamide are potently enhanced by the cAMP-dependent protein kinase. J Neurochem 2001; 77:1660-3; PMID:11413249; http://dx.doi.org/10.1046/j.1471-4159.2001.00406.x
  • Elattar TM, Lin HS. The relationship between inflammation and cAMP level in human gingiva. J Dent Res 1981; 60:674-6; PMID:6259227; http://dx.doi.org/10.1177/00220345810600030101
  • Malmberg AB, Brandon EP, Idzerda RL, Liu H, McKnight GS, Basbaum AI. Diminished inflammation and nociceptive pain with preservation of neuropathic pain in mice with a targeted mutation of the type I regulatory subunit of cAMP-dependent protein kinase. J Neurosci 1997; 17:7462-70; PMID:9295392
  • Naik SR. Increased cyclic AMP-phosphodiesterase activity during inflammation and its inhibition by anti-inflammatory drugs. Eur J Pharmacol 1984; 104:253-9; PMID:6094215; http://dx.doi.org/10.1016/0014-2999(84)90400-X
  • Hu HJ, Bhave G, Gereau RWT. Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia. J Neurosci 2002; 22:7444-52; PMID:12196566
  • Rathee PK, Distler C, Obreja O, Neuhuber W, Wang GK, Wang SY, Nau C, Kress M. PKA/AKAP/VR-1 module: A common link of Gs-mediated signaling to thermal hyperalgesia. J Neurosci 2002; 22:4740-5; PMID:12040081
  • Lee SY, Lee JH, Kang KK, Hwang SY, Choi KD, Oh U. Sensitization of vanilloid receptor involves an increase in the phosphorylated form of the channel. Arch Pharm Res 2005; 28:405-12; PMID:15918513; http://dx.doi.org/10.1007/BF02977669
  • Ji RR. Mitogen-activated protein kinases as potential targets for pain killers. Curr Opin Investig Drugs 2004; 5:71-5; PMID:14983977
  • Thomas GM, Huganir RL. MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 2004; 5:173-83; PMID:14976517; http://dx.doi.org/10.1038/nrn1346
  • Ji RR, Kawasaki Y, Zhuang ZY, Wen YR, Zhang YQ. Protein kinases as potential targets for the treatment of pathological pain. Handb Exp Pharmacol 2007:359-89; PMID:17087130
  • Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995; 9:726-35; PMID:7601337
  • Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 1999; 79:143-80; PMID:9922370
  • Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life sciences 2004; 74:2643-53; PMID:15041446; http://dx.doi.org/10.1016/j.lfs.2004.01.007
  • Bao Y, Hou W, Hua B. Protease-activated receptor 2 signalling pathways: a role in pain processing. Expert Opin Ther Targets 2014; 18:15-27; PMID:24147628; http://dx.doi.org/10.1517/14728222.2014.844792
  • Bao Y, Hou W, Liu R, Gao Y, Kong X, Yang L, Shi Z, Li W, Zheng H, Jiang S, et al. PAR2-mediated upregulation of BDNF contributes to central sensitization in bone cancer pain. Mol Pain 2014; 10:28; PMID:24886294; http://dx.doi.org/10.1186/1744-8069-10-28
  • Bao Y, Hou W, Yang L, Liu R, Gao Y, Kong X, Shi Z, Li W, Zheng H, Jiang S, et al. Increased expression of protease-activated receptor 2 and 4 within dorsal root Ganglia in a rat model of bone cancer pain. J Mol Neurosci 2015; 55:706-14; PMID:25344153; http://dx.doi.org/10.1007/s12031-014-0409-1
  • Bao Y, Hua B, Hou W, Shi Z, Li W, Li C, Chen C, Liu R, Qin Y. Involvement of protease-activated receptor 2 in nociceptive behavior in a rat model of bone cancer. J Mol Neurosci 2014; 52:566-76; PMID:24057889; http://dx.doi.org/10.1007/s12031-013-0112-7
  • Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain 1995; 62:259-74; PMID:8657426; http://dx.doi.org/10.1016/0304-3959(95)00073-2
  • Mayer DJ, Mao J, Holt J, Price DD. Cellular mechanisms of neuropathic pain, morphine tolerance, and their interactions. Proc Natl Acad Sci U S A 1999; 96:7731-6; PMID:10393889; http://dx.doi.org/10.1073/pnas.96.14.7731
  • King T, Ossipov MH, Vanderah TW, Porreca F, Lai J. Is paradoxical pain induced by sustained opioid exposure an underlying mechanism of opioid antinociceptive tolerance? Neuro-Signals 2005; 14:194-205; PMID:16215302; http://dx.doi.org/10.1159/000087658
  • Ossipov MH, Lai J, King T, Vanderah TW, Porreca F. Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers 2005; 80:319-24; PMID:15795927; http://dx.doi.org/10.1002/bip.20254
  • Ma W, Zheng WH, Powell K, Jhamandas K, Quirion R. Chronic morphine exposure increases the phosphorylation of MAP kinases and the transcription factor CREB in dorsal root ganglion neurons: an in vitro and in vivo study. Eur J Neurosci 2001; 14:1091-104; PMID:11683901; http://dx.doi.org/10.1046/j.0953-816x.2001.01731.x
  • Chen Y, Sommer C. The role of mitogen-activated protein kinase (MAPK) in morphine tolerance and dependence. Mol Neurobiol 2009; 40:101-7; PMID:19468867; http://dx.doi.org/10.1007/s12035-009-8074-z
  • Li LY, Chang KJ. The stimulatory effect of opioids on mitogen-activated protein kinase in Chinese hamster ovary cells transfected to express mu-opioid receptors. Mol Pharmacol 1996; 50:599-602; PMID:8794899
  • Gutstein HB, Rubie EA, Mansour A, Akil H, Woodgett JR. Opioid effects on mitogen-activated protein kinase signaling cascades. Anesthesiology 1997; 87:1118-26; PMID:9366464; http://dx.doi.org/10.1097/00000542-199711000-00016
  • Ferrer-Alcon M, Garcia-Fuster MJ, La Harpe R, Garcia-Sevilla JA. Long-term regulation of signalling components of adenylyl cyclase and mitogen-activated protein kinase in the pre-frontal cortex of human opiate addicts. J Neurochem 2004; 90:220-30; PMID:15198681; http://dx.doi.org/10.1111/j.1471-4159.2004.02473.x
  • Trapaidze N, Gomes I, Cvejic S, Bansinath M, Devi LA. Opioid receptor endocytosis and activation of MAP kinase pathway. Brain Res Mol Brain Res 2000; 76:220-8; PMID:10762697; http://dx.doi.org/10.1016/S0169-328X(00)00002-4
  • Bilecki W, Zapart G, Ligeza A, Wawrzczak-Bargiela A, Urbanski MJ, Przewlocki R. Regulation of the extracellular signal-regulated kinases following acute and chronic opioid treatment. Cell Mol Life Sci 2005; 62:2369-75; PMID:16158186; http://dx.doi.org/10.1007/s00018-005-5277-y
  • Li SX, Wang ZR, Li J, Peng ZG, Zhou W, Zhou M, Lu L. Inhibition of Period1 gene attenuates the morphine-induced ERK-CREB activation in frontal cortex, hippocampus, and striatum in mice. Am J Drug Alcohol abuse 2008; 34:673-82; PMID:18850497; http://dx.doi.org/10.1080/00952990802308197
  • Eitan S, Bryant CD, Saliminejad N, Yang YC, Vojdani E, Keith D, Jr., Polakiewicz R, Evans CJ. Brain region-specific mechanisms for acute morphine-induced mitogen-activated protein kinase modulation and distinct patterns of activation during analgesic tolerance and locomotor sensitization. J Neurosci 2003; 23:8360-9; PMID:12967998
  • Muller DL, Unterwald EM. In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine. J Pharmacol Exp Ther 2004; 310:774-82; PMID:15056728; http://dx.doi.org/10.1124/jpet.104.066548
  • Schulz S, Hollt V. Opioid withdrawal activates MAP kinase in locus coeruleus neurons in morphine-dependent rats in vivo. Eur J Neurosci 1998; 10:1196-201; PMID:9753188; http://dx.doi.org/10.1046/j.1460-9568.1998.00103.x
  • Cao JL, He JH, Ding HL, Zeng YM. Activation of the spinal ERK signaling pathway contributes naloxone-precipitated withdrawal in morphine-dependent rats. Pain 2005; 118:336-49; PMID:16289800; http://dx.doi.org/10.1016/j.pain.2005.09.006
  • Zhuang ZY, Xu H, Clapham DE, Ji RR. Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. J Neurosci 2004; 24:8300-9; PMID:15385613; http://dx.doi.org/10.1523/JNEUROSCI.2893-04.2004
  • Cui Y, Chen Y, Zhi JL, Guo RX, Feng JQ, Chen PX. Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance. Brain Res 2006; 1069:235-43; PMID:16403466; http://dx.doi.org/10.1016/j.brainres.2005.11.066
  • Hayward MD, Duman RS, Nestler EJ. Induction of the c-fos proto-oncogene during opiate withdrawal in the locus coeruleus and other regions of rat brain. Brain Res 1990; 525:256-66; PMID:1701330; http://dx.doi.org/10.1016/0006-8993(90)90872-9
  • Couceyro P, Douglass J. Precipitated morphine withdrawal stimulates multiple activator protein-1 signaling pathways in rat brain. Mol Pharmacol 1995; 47:29-39; PMID:7838131
  • Fan XL, Zhang JS, Zhang XQ, Ma L. Chronic morphine treatment and withdrawal induce up-regulation of c-Jun N-terminal kinase 3 gene expression in rat brain. Neuroscience 2003; 122:997-1002; PMID:14643766; http://dx.doi.org/10.1016/j.neuroscience.2003.08.062
  • Gardell LR, Wang R, Burgess SE, Ossipov MH, Vanderah TW, Malan TP, Jr., Lai J, Porreca F. Sustained morphine exposure induces a spinal dynorphin-dependent enhancement of excitatory transmitter release from primary afferent fibers. J Neurosci 2002; 22:6747-55; PMID:12151554
  • Tiong GK, Pierce TL, Olley JE. Sub-chronic exposure to opiates in the rat: effects on brain levels of substance P and calcitonin gene-related peptide during dependence and withdrawal. J Neurosci Res 1992; 32:569-75; PMID:1382137; http://dx.doi.org/10.1002/jnr.490320412
  • Welch SP, Bass PP, Olson KG, Pugh G. Morphine-induced modulation of calcitonin gene-related peptide levels. Pharmacol Biochem Behavior 1992; 43:1107-16; PMID:1335576; http://dx.doi.org/10.1016/0091-3057(92)90489-3
  • Gu G, Kondo I, Hua XY, Yaksh TL. Resting and evoked spinal substance P release during chronic intrathecal morphine infusion: parallels with tolerance and dependence. J Pharmacol Exp Ther 2005; 314:1362-9; PMID:15908510; http://dx.doi.org/10.1124/jpet.105.087718
  • Salmon AM, Damaj MI, Marubio LM, Epping-Jordan MP, Merlo-Pich E, Changeux JP. Altered neuroadaptation in opiate dependence and neurogenic inflammatory nociception in alpha CGRP-deficient mice. Nat Neurosci 2001; 4:357-8; PMID:11276224; http://dx.doi.org/10.1038/86001
  • Murtra P, Sheasby AM, Hunt SP, De Felipe C. Rewarding effects of opiates are absent in mice lacking the receptor for substance P. Nature 2000; 405:180-3; PMID:10821273; http://dx.doi.org/10.1038/35012069
  • Guo A, Vulchanova L, Wang J, Li X, Elde R. Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2×3 purinoceptor and IB4 binding sites. Eur J neuroscience 1999; 11:946-58; PMID:10103088; http://dx.doi.org/10.1046/j.1460-9568.1999.00503.x
  • Tang HB, Li YS, Miyano K, Nakata Y. Phosphorylation of TRPV1 by neurokinin-1 receptor agonist exaggerates the capsaicin-mediated substance P release from cultured rat dorsal root ganglion neurons. Neuropharmacology 2008; 55:1405-11; PMID:18809416; http://dx.doi.org/10.1016/j.neuropharm.2008.08.037
  • Tang HB, Nakata Y. The activation of transient receptor potential vanilloid receptor subtype 1 by capsaicin without extracellular Ca2+ is involved in the mechanism of distinct substance P release in cultured rat dorsal root ganglion neurons. Naunyn-Schmiedeberg's Arch pharmacol 2008; 377:325-32; PMID:18034335; http://dx.doi.org/10.1007/s00210-007-0211-5
  • Li DP, Chen SR, Pan HL. VR1 receptor activation induces glutamate release and postsynaptic firing in the paraventricular nucleus. J Neurophysiol 2004; 92:1807-16; PMID:15115794; http://dx.doi.org/10.1152/jn.00171.2004
  • Lappin SC, Randall AD, Gunthorpe MJ, Morisset V. TRPV1 antagonist, SB-366791, inhibits glutamatergic synaptic transmission in rat spinal dorsal horn following peripheral inflammation. Eur J Pharmacol 2006; 540:73-81; PMID:16737693; http://dx.doi.org/10.1016/j.ejphar.2006.04.046
  • Otsuka M, Yoshioka K. Neurotransmitter functions of mammalian tachykinins. Physiol Rev 1993; 73:229-308; PMID:7682720
  • Schicho R, Donnerer J, Liebmann I, Lippe IT. Nociceptive transmitter release in the dorsal spinal cord by capsaicin-sensitive fibers after noxious gastric stimulation. Brain Res 2005; 1039:108-15; PMID:15781052; http://dx.doi.org/10.1016/j.brainres.2005.01.050
  • Rigoni M, Trevisani M, Gazzieri D, Nadaletto R, Tognetto M, Creminon C, Davis JB, Campi B, Amadesi S, Geppetti P, et al. Neurogenic responses mediated by vanilloid receptor-1 (TRPV1) are blocked by the high affinity antagonist, iodo-resiniferatoxin. Br J Pharmacol 2003; 138:977-85; PMID:12642400; http://dx.doi.org/10.1038/sj.bjp.0705110
  • Aimone LD, Yaksh TL. Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo. Peptides 1989; 10:1127-31; PMID:2482963; http://dx.doi.org/10.1016/0196-9781(89)90003-X
  • Jin S, Lei L, Wang Y, Da D, Zhao Z. Endomorphin-1 reduces carrageenan-induced fos expression in the rat spinal dorsal horn. Neuropeptides 1999; 33:281-4; PMID:10657505; http://dx.doi.org/10.1054/npep.1999.0040
  • Zhou Q, Karlsson K, Liu Z, Johansson P, Le Greves M, Kiuru A, Nyberg F. Substance P endopeptidase-like activity is altered in various regions of the rat central nervous system during morphine tolerance and withdrawal. Neuropharmacology 2001; 41:246-53; PMID:11489461; http://dx.doi.org/10.1016/S0028-3908(01)00055-7
  • Dickenson AH. Spinal cord pharmacology of pain. Br J anaesthesia 1995; 75:193-200; PMID:7577253; http://dx.doi.org/10.1093/bja/75.2.193

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.