Top

Published in:

01-06-2009 | Review

Mode of action of cannabinoids on nociceptive nerve endings

Authors: Michaela Kress, R. Kuner

Published in: Experimental Brain Research | Issue 1/2009

Abstract

In recent years, cannabinoids have emerged as attractive alternatives or supplements to therapy for chronic pain states. However, in humans the activation of cannabinoid receptors in neurons of the central nervous system is associated with psychotropic side effects, temporary memory impairment and dependence, which arise via the effects of cannabinoids on forebrain circuits. For clinical exploitation of the analgesic properties of cannabinoids, a major challenge is to devise strategies that reduce or abolish their adverse effects on cognitive, affective and motor functions without attenuating their analgesic effects. The cannabinoid receptor family currently includes two cloned metabotropic receptors: CB1, CB2 and possibly GPR55 which are distributed widely across many key loci in pain-modulating pathways, including the peripheral terminals of primary afferents. Modulation of transducer ion channels expressed at nociceptive terminals occurs upon activation of metabotropic cannabinoid receptors, but direct cannabinoid action on ion channels involved in sensory transduction or regulation of neuron excitability likely contributes to the peripheral cannabinoid effects.

Agarwal N, Pacher P, Tegeder I, Amaya F, Constantin CE, Brenner GJ, Rubino T, Michalski CW, Marsicano G, Monory K, Mackie K, Marian C, Batkai S, Parolaro D, Fischer MJ, Reeh W, Kunos G, Kress M, Lutz B, Woolf CJ, Kuner R (2007) Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci 10:870–879PubMedCrossRef

Ahluwalia J, Urban L, Capogna M, Bevan S, Nagy I (2000) Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons. Neuroscience 100:685–688PubMedCrossRef

Ahluwalia J, Urban L, Bevan S, Capogna M, Nagy I (2002) Cannabinoid 1 receptors are expressed by nerve growth factor- and glial cell-derived neurotrophic factor-responsive primary sensory neurones. Neuroscience 110:747–753PubMedCrossRef

Akopian AN, Ruparel NB, Patwardhan AM, Hargreaves KM (2008) Cannabinoids desensitize capsaicin and mustard oil responses in sensory neurons via TRPA1 activation. J Neurosci 30:1064–1075CrossRef

Akopian AN, Ruparel NB, Jeske NA, Patwardahan AM, Hargreaves KM (2009) Role of ionotropic cannabinoid receptors in peripheral antinociception and antihyperalgesia. Trends Pharmacol Sci (in press)

Amaya F, Shimosato G, Kawasaki Y, Hashimoto S, Tanaka Y, Ji RR, Tanaka M (2006) Induction of CB1 cannabinoid receptor by inflammation in primary afferent neurons facilitates antihyperalgesic effect of peripheral CB1 agonist. Pain 124:175–183PubMedCrossRef

Anand U, Otto WR, Sanchez-Herrera D, Facer P, Yiangou Y, Korchev Y, Birch R, Benham C, Bountra C, Chessel IP, Anand P (2008) Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain 138:667–680PubMedCrossRef

Ashton JC, Milligan ED (2008) Cannabinoids for the treatment of neuropathic pain: clinical evidence. Curr Opin Invest Drugs 9:65–75

Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D (2006) TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–1282PubMedCrossRef

Beltramo M, Stella N, Calignano A, Lin SY, Makriyannis A, Piomelli D (1997) Functional role of high-affinity anandamide transport, as revealed by selective inhibition. Science 277:1097CrossRef

Beltramo M, Bernardini N, Bertorelli R, Campanella M, Nicolussi E, Fredduzzi S, Reggiani A (2006) CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur J Neurosci 23:1530–1538PubMedCrossRef

Belvisi MG, Patel HJ, Freund-Michel V, Hele DJ, Crispino N, Birrell MA (2008) Inhibitory activity of the novel CB2 receptor agonist GW833972A on guinea-pig and human sensory nerve function in the airways. Br J Pharmacol 155:547–557PubMedCrossRef

Binzen U, Greffrath W, Hennessy S, Bausen M, Saaler-Reinhardt S, Treede RD (2006) Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons. Neuroscience 142:527–539PubMedCrossRef

Bridges D, Rice AS, Egertová M, Elphick MR, Winter J, Michael GJ (2003) Localisation of cannabinoid receptor 1 in rat dorsal root ganglion using in situ hybridisation and immunohistochemistry. Neuroscience 119:812CrossRef

Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824PubMedCrossRef

Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D (1999) A capsaicin-receptor homologue with a high threshold for noxious heat. Nature 398:436–441PubMedCrossRef

Chuang HH, Prescott ED, Kong H, Shields S, Jordt S-E, Basbaum AI, Chao MV, Julius D (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4, 5)P2-mediated inhibition. Nature 411:957–962PubMedCrossRef

Coutts AA, Irving AJ, Mackie K, Pertwee RG, Anavi-Goffer S (2002) Localisation of cannabinoid CB1 receptor immunoreactivity in the guinea pig and rat myenteric plexus. J Comp Neurol 448:410–422PubMedCrossRef

Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA (2000) Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature 405:183–187PubMedCrossRef

De Petrocellis L, Vellani V, Schiano-Moriello A, Marini P, Magherini PC, Orlando P, Di Marzo V (2008) Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8. J Pharmacol Exp Ther 325:1007–1015PubMedCrossRef

Di Marzo V (2006) Endocannabinoids: synthesis and degradation. Rev Physiol Biochem Pharmacol 160:1–24CrossRef

Di Marzo V, Fontana A, Cadas H, Schinelli S, Cimino G, Schwartz JC, Piomelli D (1994) Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 372:686–691PubMedCrossRef

Di Marzo V, Bifulco M, De Petrocellis L (2004) The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 3:771–784PubMedCrossRef

Dinh TP, Freund TF, Piomelli D (2002) A role for monoglyceride lipase in 2-arachidonoylglycerol inactivaiton. Chem Phys Lipids 121:149–158PubMedCrossRef

Elmes SJ, Jhaveri MD, Smart D, Kendall DA, Chapman V (2004) Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naive rats and in rat models of inflammatory and neuropathic pain. Eur J Neurosci 20:2320CrossRef

Evans RM, Wease KN, MacDonald CJ, Khairy HA, Ross RA, Scott RH (2008) Modulation of sensory neuron potassium conductances by anandamide indicates roles for metabolites. Br J Pharmacol 154:480–492PubMedCrossRef

Fan P (1995) Cannabinoid agonist inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons. J Neurophysiol 73:910

Fegley D, Kathuria S, Mercier R, Li C, Goutopoulos A, Makriyannis A, Piomelli D (2004) Anandamide transport is independent of fatty-acid amide hydrolase activity and is blocked by the hydrolysis-resistant inhibitor AM1172. Proc Natl Acad Sci USA 101:8756–8761PubMedCrossRef

Fernandez-Ruiz J, Romero J, Velasco G, Tolon RM, Ramos JA, Guzman M (2007) Cannabinoid CB2 receptor: a new target for controlling neural cell survival. Trends Pharmacol Sci 28:39–45PubMedCrossRef

Fischbach T, Greffrath W, Nawrath H, Treede R-D (2007) Effects of anandamide and noxious heat on intracellular calcium concentration in nociceptive DRG neurons of the rat. J Neurophysiol 98:929–938PubMedCrossRef

Freund TF, Katona I, Piomelli D (2003) Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 83:1017–1066PubMed

Guerrero AV, Quang P, Dekker N, Jordan RCK, Schmidt BL (2008) Peripheral cannabinoids attenuate carcinoma-induced nociception in mice. Neurosci Lett 433:77–81PubMedCrossRef

Guindon J, Hohmann AG (2008) Cannabinoid CB2 receptors: a therapeutic target for the treatment of inflammatory and neuropathic pain. Br J Pharmacol 153:319–334PubMedCrossRef

Handwerker HO, Reeh PW, Steen KH (1990) Effects of 5HT on nociceptors. In: Besson J-M (ed) Serotonin and pain. Elsevier, Amsterdam, pp 1–15

Hillard CJ, Edgemond WS, Jarrahian A, Campbell WB (1997) Accumulation of N-arachidonoylethanolamine (anandamide) into cerebellar granule cells occurs via facilitated diffusion. J Neurochem 69:631–638PubMedCrossRef

Hillsley K, McCaul C, Aerssens J, Peeters PJ, Gijsen H, Moechars D, Coulie B, Grundy D, Stead RH (2007) Activation of the cannabinoid 2 (CB2) receptor inhibits murine mesenteric afferent nerve activity. Neurogastroenterol Motil 19:769–777PubMedCrossRef

Hohmann AG, Herkenham M (1999) Localization of central cannabinoid CB1 receptor messenger RNA in neuronal subpopulations of rat dorsal root ganglia: a double-label in situ hybridization study. Neuroscience 90:923–931PubMedCrossRef

Howlett AC (2005) Cannabinoid receptor signaling. Handb Exp Pharmacol 53–79

Ibrahim MM, Deng H, Zvonok AM, Cockayne DA, Kwan J, Mata H, Vanderah TW, Lai J, Porreca F, Makriyannis A, Malan TP (2003) Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci USA 100:10529–10533PubMedCrossRef

Ibrahim MM, Porreca F, Lai J, Albrecht PJ, Rice FL, Khodorova A, Davar G, Makriyannis A, Vanderah TW, Mata H, Malan TP (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci USA 102:3093–3098PubMedCrossRef

Ibrahim MM, Rude ML, Stagg NJ, Mata HP, Lai J, Vanderah TW, Porreca F, Veerappan V, Tian X, George C, Parrish DA, Papahatjis DP, Makriyannis A (2006) CB2 cannabinoid receptor mediation of antinociception. Pain 122:36–42PubMedCrossRef

Jerman JC, Gray J, Brough SJ, Ooi L, Owen D, Davis JB, Smart D (2002) Comparison of effects of anandamide at recombinant and endogenous rat vanilloid receptors. Br J Anaesth 89:882–887PubMedCrossRef

Jeske NA, Patwardahan AM, Gamper N, Price TJ, Akopian AN, Hargreaves KM (2006) Cannabinoid WN55, 212-2 regulates TRPV1 phosphorylation in sensory neurons. J Biol Chem 281:32879–32890PubMedCrossRef

Jhaveri MD, Sagar DR, Elmes SJ, Kendall DA, Chapman V (2007) Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain. Mol Neurobiol 36:26–35PubMedCrossRef

Jordt S-E, McKemy DD, Julius D (2003) Lessons from peppers and peppermint: the molecular logic of thermosensation. Curr Opin Neurobiol 13:487–492PubMedCrossRef

Kelly S, Donaldson LF (2008) Peripheral cannabinoid CB1 receptors inhibit evoked responses of nociceptive neurons in vivo. Eur J Pharmacol 586:160–163PubMedCrossRef

Kelly S, Jhaveri MD, Sagar DR, Kendall DA, Chapman V (2003) Activation of peripheral cannabinoid CB1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation. Eur J Neurosci 18:2239–2243PubMedCrossRef

Khanolkar AD, Lu D, Ibrahim MM, Duclos RI, Thakur GA, Malan TP, Porreca F, Veerappan V, Tian X, George C, Parrish DA, Papahatjis DP, Makriyannis A (2007) Cannabilactones: a novel class of CB2 selective agonists with peripheral analgesic activity. J Med Chem 50:6493–6500PubMedCrossRef

Khasabova IA, Simone DA, Seybold VS (2002) Cannabinoids attenuate depolarization-dependent Ca²⁺ influx in intermediate-size primary afferent neurons of adult rats. Neuroscience 115:613–625PubMedCrossRef

Khasabova IA, Harding-Rose C, Simone DA, Seybold VS (2004) Differential effects of CB1 and opioid agonists on two populations of adult rat dorsal root ganglion neurons. J Neurosci 24:1744–1753PubMedCrossRef

Khasabova IA, Khasabov SG, Harding-Rose C, Coicou LG, Seybold BA, Lindberg AE, Steevens CD, Simone DA, Seybold VS (2008) A decrease in anandamide signaling contributes to the maintenance of cutaneous mechanical hyperalgesia in a model of bone cancer pain. J Neurosci 28:11141–11152PubMedCrossRef

Kim HI, Kim TH, Shin YK, Lee CS, Park M, Song J-H (2005) Anandamide suppression of Na⁺ currents in rat dorsal root ganglion neurons. Brain Res 1062:39–47PubMedCrossRef

Krishtal O, Lozovaya N, Fedorenko A, Savelyev I, Chizhamakov I (2006) The agonists for nociceptors are ubiquitous, but the modulators are specific: P2X receptors in the sensory neurons are modulated by cannabinoids. Pflugers Arch Eur J Physiol 453:353–360CrossRef

La Rana G, Russo R, Campolongo P, Bortolato M, Mangieri RA, Cuomo V, Iacono A, Mattace Raso G, Meli R, Piomelli D, Calignano A (2008) Modulation of neuropathic and inflammatory pain by the endocannabinoid transport inhibitor AM404 [N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide]. J Pharmacol Exp Ther 317:1365–1371CrossRef

Lauckner JE, Hille B, Mackie K (2005) The cannabinoid agonist WIN55, 212-2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc Natl Acad Sci USA 102:19144–19149PubMedCrossRef

Lauckner JE, Jenson JB, Chen H-Y, Lu H-C, Hille B, Mackie K (2008) GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M currents. Proc Natl Acad Sci USA 105:2699–2704PubMedCrossRef

Ligresti A, Morera E, van der Stelt M, Monory K, Lutz B, Ortar G, Di Marzo V (2004) Further evidence for the existence of a specific process for the membrane transport of anandamide. Biochem J 380:265–272PubMedCrossRef

Mackie K, Stella N (2006) Cannabinoid receptors and endocannabinoids: evidence for new players. Am Assoc Pharm Sci J 8:E298–E306

Maingret F, Patel AJ, Lazdunski M, Honore E (2001) The endocannabinoid anandamide is a direct and selective blocker of the background K⁺ channel TASK-1. EMBO J 20:47–54PubMedCrossRef

Malan TP, Ibrahim MM, Deng H, Liu Q, Mata H, Vanderah TW, Porreca F, Makriyannis A (2001) CB2 cannabinoid receptor-mediated peripheral antinociception. Pain 93:239–245PubMedCrossRef

Malan TP, Ibrahim MM, Vanderah TW, Makriyannis A, Porreca F (2002) Inhibition of pain responses by activation of CB2 cannabinoid receptors. Chem Phys Lipids 121:191–200PubMedCrossRef

Marsicano G, Goodenough S, Monory K, Hermann K, Eder M, Cannich A, Azad SC, Cascio MG, Gutierrez SO, van der Stelt M, Lopez-Rodriguez ML, Casanova E, Schütz G, Zieglgänsberger W, Di Marzo V, Behl C, Lutz B (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 302:84–88PubMedCrossRef

Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564PubMedCrossRef

Mitrirattanakul S, Ramakul N, Guerrero AV, Matsuka Y, Ono T, Iwase H, Mackie K, Faull KF, Spigelman I (2006) Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain. Pain 126:102–114PubMedCrossRef

Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Brudford EA, Caterina MJ, Clapham CE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX (2002) A unified nomenclature for the superfamily of TRP cation channels. Mol Cell 9:229–231PubMedCrossRef

Morisset V, Urban L (2001) Cannabinoid-induced presynaptic inhibition of glutamatergic EPSCs in substantia gelatinosa neurons of the rat spinal cord. J Neurophysiol 86:40–48PubMed

Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterisation of a peripheral receptor for cannabinoids. Nature 365:61–65PubMedCrossRef

Nackley AG, Zvonok AM, Makriyannis A, Hohmann AG (2004) Activation of cannabinoid CB2 receptors suppresses C-fiber responses and windup in spinal wide dynamic range neurons in the absence and presence of inflammation. J Neurophysiol 92:3562–3574PubMedCrossRef

Nyilas R, Dudok B, Uran GB, Mackie K, Watanabe M, Cravatt BF, Freund TF, Katona I (2008) Enzymatic machinery for endocannabinoid biosynthesis associated with calcium stores glutamatergic axon terminals. J Neurosci 28:1058–1063PubMedCrossRef

Ocana M, Cendan CM, Cobos EJ, Entrena JM, Baeyens JM (2004) Potassium channels and pain: present realities and future opportunities. Eur J Pharmacol 500:203–219PubMedCrossRef

Offermanns S (2003) G-proteins as transducers ion transmembrane signalling. Progr Biophys Mol Biol 83:101–130CrossRef

Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T (2007) Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Comm 362:928–934PubMedCrossRef

Onaivi ES, Ishiguro H, Gong JP, Patel S, Perchuk A, Meozzi PA et al (2006) Discovery of the presence and functional expression of cannabinoid CB2 receptors in the brain. Ann NY Acad Sci 1074:514–536PubMedCrossRef

Pacher P, Barkai S, Kunos G (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58:389–462PubMedCrossRef

Patel HJ, Birrell MA, Crispino N, Hele DJ, Venkatesan P, Barnes PJ et al (2003) Inhibition of guinea-pig and human sensory nerve activity and the cough reflex in guinea-pigs by cannabinoid (CB2) receptor activation. Br J Pharmacol 140:261–268PubMedCrossRef

Patwardahan AM, Jeske NA, Price TJ, Gamper N, Akopian AN, Hargreaves KM (2006) The cannabinoid WIN55, 212–2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. Proc Natl Acad Sci USA 103:11393–11398CrossRef

Potenzieri C, Brink TS, Pacharinsak C, Simone DA (2008) Cannabinoid modulation of cutaneous Aδ nociceptors during inflammation. J Neurophysiol 100:2794–2806PubMedCrossRef

Price TJ, Helesic G, Parghi D, Hargreaves KM, Flores CM (2003) The neuronal distribution of cannabinoid receptor type 1 in the trigeminal ganglion of the rat. Neuroscience 120:155–162PubMedCrossRef

Qin N, Neeper MP, Liu Y, Hutchinson TL, Lubin ML, Flores CM (2008) TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci 28:6231–6238PubMedCrossRef

Quartilho A, Mata H, Ibrahim MM, Vanderah TW, Porreca F, Makriyannis A, Malan TP (2003) Inhibition of inflammatory hyperalgesia by activation of peripheral CB2 cannabinoid receptors. Anesthesiology 99:955–960PubMedCrossRef

Rácz I, Bilkei-Gorzo A, Markert A, Stamer F, Göthert M, Zimmer A (2008) Anandamide effects on 5-HT3 receptors in vivo. Eur J Pharmacol 596:98–101PubMedCrossRef

Rimmerman N, Hughes HV, Bradshaw HB, Pazos MX, Mackie K, Prieto AL, Walker JM (2008) Compartmentalization of endocannabinoids into lipid rafts in a dorsal root ganglion cell line. Br J Pharmacol 153:380–389PubMedCrossRef

Ross RA, Coutts AA, McFarlane SM, Anavi-Goffer S, Irving AJ, Pertwee RG et al (2001) Actions of cannabinoid receptor ligands on rat cultured sensory neurons: implications for antinociception. Neuropharmacology 40:221–232PubMedCrossRef

Ross RA, Evans RM, Scott RH (2004) Cannabinoids and sensory neurons. Curr Neuropharmacol 1:59–73CrossRef

Ross HR, Napier I, Connor M (2008) Inhibition of recombinant human T-type calcium channels by Δ9-tetrahydrocannabinol and cannabidiol. J Biol Chem 283:16124–16134PubMedCrossRef

Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, Elebring T, Nilsson K, Drmota T, Greasley PJ (2007) The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 152:1092–1101PubMedCrossRef

Sagar DR, Kelly S, Millns PJ, O’Shaughnessey CT, Kendall DA, Chapman V (2005) Inhibitory effects of CB1 and CB2 receptor antagonists on responses of DRG neurons and dorsal horn neurons in neuropathic rats. Eur J Pharmacol 22:371–379

Salio C, Fischer J, Franzoni MF, Conrath M (2002) Pre- and post-synaptic localization of the CB1 cannabinoid receptor in the dorsal horn of the rat spinal cord. Neuroscience 110:755–764PubMedCrossRef

Schuelert N, McDougall JJ (2008) Cannabinoid-mediated antinociception is enhanced in rat osteoarthritic knees. Arthritis Rheum 58:145–153PubMedCrossRef

Shire D, Carillon C, Kaghad M, Calandra B, Rinaldi-Carmona M, Le Fur G, Caput D, Ferrara P (1995) An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J Biol Chem 270:3726–3731PubMedCrossRef

Ständer S, Schmelz M, Metze D, Luger T, Rukwied R (2005) Distribution of cannabinoid receptor 1 (CB1) an d2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci 38:177–188PubMedCrossRef

Starowicz K, Nigam S, Di Marzo V (2007) Biochemistry and Pharmacology of endovanilloids. Pharmacol Ther 114:13–33PubMedCrossRef

Staton PC, Hatcher JP, Walker DJ, Morrison AD, Shapland EM, Hughes JP, Chong E, Mander PK, Green PJ, Billinton A, Fulleylove M, Lancaster HC, Smith JC, Bailey LT, Wise A, Brown AJ, Richardson JC, Chessel IP (2008) The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain. Pain 139:225–236PubMedCrossRef

Tognetto M, Amadesi S, Harrison S, Creminon C, Trevisani M, Carreras M, Matera M, Geppetti P, Bianchi A (2001) Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation. J Neurosci 21:1104–1109PubMed

Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D (1998) The cloned capsaicin receptor integrates multiple pain-producing stimuli. Biophys J 21:531–543

van der Stelt M, Trevisani M, Vellani V, De Petrocellis L, Moriello AS, Campi B, McNaughton P, Geppetti P, Di Marzo V (2005) Anandamide acts as an intracellular messenger amplifying Ca²⁺ influx via TRPV1 channels. EMBO J 24:3026–3037PubMedCrossRef

Veale EL, Buswell R, Clarke CE, Mathie A (2007) Identification of a region in the TASK3 two pore domain potassium channel that is critical for its blockade by methanandamide. Br J Pharmacol 152:778–786PubMedCrossRef

Walker JM, Hohmann AG (2005) Cannabinoid mechanisms of pain suppression. Handb Exp Pharmacol 168:509–554PubMedCrossRef

Wotherspoon G, Fox A, McIntyre P, Colley S, Bevan S, Winter J (2005) Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons. Neuroscience 135:235–245PubMedCrossRef

Yao BB, Hsieh GC, Frost JM, Fan Y, Garrison TR, Daza AV, Grayson GK, Zhu CZ, Pai M, Chandran P, Salyers AK, Wensink EJ, Honore P, Sullivan JP, Dart MJ, Meyer MD (2008) In vitro and in vivo characterization of A-796260: a selective cannabinoid CB2 receptor agonist exhibiting analgesic activity in rodent pain models. Br J Pharmacol 153:401CrossRef

Yiangou Y, Facer P, Smith JA, Sangameswaran L, Eglen R, Birch R, Knowles C, Williams N, Anand P (2001) Increased acid-sensing ion channel ASIC-3 in inflamed human intestine. Eur J Gastroenterol Hepatol 13:891–896PubMedCrossRef

Zygmunt PM, Andersson DA, Hogestatt ED (2002) Delta 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism. J Neurosci 22:4720–4727PubMed

Title: Mode of action of cannabinoids on nociceptive nerve endings
Authors: Michaela Kress
R. Kuner
Publication date: 01-06-2009
Publisher: Springer-Verlag
Published in: Experimental Brain Research / Issue 1/2009
Print ISSN: 0014-4819
Electronic ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-009-1762-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mode of action of cannabinoids on nociceptive nerve endings

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2009

Mode of action of cytokines on nociceptive neurons

Differential effects of TRPV channel block on polymodal activation of rat cutaneous nociceptors in vitro

Converting cold into pain

Editorial

The role of TRPV1 receptors in pain evoked by noxious thermal and chemical stimuli

Algesic agents exciting muscle nociceptors