Skip to main content
Log in

Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The endocannabinoid system consists of cannabinoid CB1 and CB2 receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB1 receptors. Following the recent evidence for CB2 receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB2 receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB2 receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB2 receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

SNL:

spinal nerve ligation

CCI:

chronic constriction injury

CB1 :

cannabinoid CB1 receptor

CB2 :

cannabinoid CB2 receptor

DRG:

dorsal root ganglion

PEA:

palmitoyl ethanolamide

References

  1. Gaoni Y, Mechoulam R (1964) Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 86:1646–1647

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  4. Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279:129–134

    PubMed  CAS  Google Scholar 

  5. Chakrabarti A, Onaivi ES, Chaudhuri G (1995) Cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid receptor protein. DNA Seq 5:385–388

    PubMed  CAS  Google Scholar 

  6. Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessegue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P (1996) Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim Biophys Acta 1307:132–136

    PubMed  Google Scholar 

  7. Griffin G, Tao Q, Abood ME (2000) Cloning and pharmacological characterization of the rat CB(2) cannabinoid receptor. J Pharmacol Exp Ther 292:886–894

    PubMed  CAS  Google Scholar 

  8. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, Mechoulam R, Pertwee RG (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202

    Article  PubMed  CAS  Google Scholar 

  9. Walker JM, Huang SM (2002) Cannabinoid analgesia. Pharmacol Ther 95:127–135

    Article  PubMed  CAS  Google Scholar 

  10. Pertwee RG (2001) Cannabinoid receptors and pain. Prog Neurobiol 63:569–611

    Article  PubMed  CAS  Google Scholar 

  11. Rice AS, Farquhar-Smith WP, Nagy I (2002) Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. Prostaglandins Leukot Essent Fatty Acids 66:243–256

    Article  PubMed  CAS  Google Scholar 

  12. Hohmann AG (2002) Spinal and peripheral mechanisms of cannabinoid antinociception: behavioral, neurophysiological and neuroanatomical perspectives. Chem Phys Lipids 121:173–190

    Article  PubMed  CAS  Google Scholar 

  13. Walker JM, Krey JF, Chu CJ, Huang SM (2002) Endocannabinoids and related fatty acid derivatives in pain modulation. Chem Phys Lipids 121:159–172

    Article  PubMed  CAS  Google Scholar 

  14. Mackie K (2006) Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol 46:101–122

    Article  PubMed  CAS  Google Scholar 

  15. Malan TP Jr, Ibrahim MM, Lai J, Vanderah TW, Makriyannis A, Porreca F (2003) CB2 cannabinoid receptor agonists: pain relief without psychoactive effects? Curr Opin Pharmacol 3:62–67

    Article  PubMed  CAS  Google Scholar 

  16. Chapman V, Finn DP (2003) Analgesic effects of cannabinoids: sites and mechanisms of action. Rev Analg 7:25–39

    Article  CAS  Google Scholar 

  17. Finn DP, Chapman V (2004) Cannabinoids as analgesic agents: evidence from in vivo studies. Curr Neuropharmacol 2:75–89

    Article  CAS  Google Scholar 

  18. Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM (1998) Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 83:393–411

    Article  PubMed  CAS  Google Scholar 

  19. Egertova M, Elphick MR (2000) Localisation of cannabinoid receptors in the rat brain using antibodies to the intracellular C-terminal tail of CB. J Comp Neurol 422:159–171

    Article  PubMed  CAS  Google Scholar 

  20. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC (1991) Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. J Neurosci 11:563–583

    PubMed  CAS  Google Scholar 

  21. Ross RA, Coutts AA, McFarlane SM, Anavi-Goffer S, Irving AJ, Pertwee RG, MacEwan DJ, Scott RH (2001) Actions of cannabinoid receptor ligands on rat cultured sensory neurones: implications for antinociception. Neuropharmacology 40:221–232

    Article  PubMed  CAS  Google Scholar 

  22. Hohmann AG, Herkenham M (1999) Cannabinoid receptors undergo axonal flow in sensory nerves. Neuroscience 92:1171–1175

    Article  PubMed  CAS  Google Scholar 

  23. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61

    Article  PubMed  CAS  Google Scholar 

  24. Nunez E, Benito C, Pazos MR, Barbachano A, Fajardo O, Gonzalez S, Tolon RM, Romero J (2004) Cannabinoid CB2 receptors are expressed by perivascular microglial cells in the human brain: an immunohistochemical study. Synapse 53:208–213

    Article  PubMed  CAS  Google Scholar 

  25. Carlisle SJ, Marciano-Cabral F, Staab A, Ludwick C, Cabral GA (2002) Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Int Immunopharmacol 2:69–82

    Article  PubMed  CAS  Google Scholar 

  26. Carrier EJ, Kearn CS, Barkmeier AJ, Breese NM, Yang W, Nithipatikom K, Pfister SL, Campbell WB, Hillard CJ (2004) Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol 65:999–1007

    Article  PubMed  CAS  Google Scholar 

  27. Facchinetti F, Del Giudice E, Furegato S, Passarotto M, Leon A (2003) Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide. Glia 41:161–168

    Article  PubMed  Google Scholar 

  28. Klegeris A, Bissonnette CJ, McGeer PL (2003) Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br J Pharmacol 139:775–786

    Article  PubMed  CAS  Google Scholar 

  29. Walter L, Franklin A, Witting A, Wade C, Xie Y, Kunos G, Mackie K, Stella N (2003) Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23:1398–1405

    PubMed  CAS  Google Scholar 

  30. Ashton JC, Friberg D, Darlington CL, Smith PF (2006) Expression of the cannabinoid CB2 receptor in the rat cerebellum: an immunohistochemical study. Neurosci Lett 396:113–116

    Article  PubMed  CAS  Google Scholar 

  31. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332

    Article  PubMed  CAS  Google Scholar 

  32. Gong JP, Onaivi ES, Ishiguro H, Liu QR, Tagliaferro PA, Brusco A, Uhl GR (2006) Cannabinoid CB2 receptors: immunohistochemical localization in rat brain. Brain Res 1071:10–23

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  34. Stander S, Schmelz M, Metze D, Luger T, Rukwied R (2005) Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci 38:177–188

    Article  PubMed  CAS  Google Scholar 

  35. Walczak JS, Pichette V, Leblond F, Desbiens K, Beaulieu P (2005) Behavioral, pharmacological and molecular characterization of the saphenous nerve partial ligation: a new model of neuropathic pain. Neuroscience 132:1093–1102

    Article  PubMed  CAS  Google Scholar 

  36. Walczak JS, Pichette V, Leblond F, Desbiens K, Beaulieu P (2006) Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes. J Neurosci Res 83:1310–1322

    Article  PubMed  CAS  Google Scholar 

  37. 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 23:1530–1538

    Article  PubMed  CAS  Google Scholar 

  38. 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 135:235–245

    Article  PubMed  CAS  Google Scholar 

  39. Ross RA, Gibson TM, Brockie HC, Leslie M, Pashmi G, Craib SJ, Di Marzo V, Pertwee RG (2001) Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. Br J Pharmacol 132:631–640

    Article  PubMed  CAS  Google Scholar 

  40. 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 120:155–162

    Article  PubMed  CAS  Google Scholar 

  41. Hanus L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, Pertwee RG, Ross RA, Mechoulam R, Fride E (1999) HU-308: a specific agonist for CB(2), a peripheral cannabinoid receptor. Proc Natl Acad Sci USA 96:14228–14233

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  43. Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, Leon A (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci U S A 92:3376–3380

    Article  PubMed  CAS  Google Scholar 

  44. Mazzari S, Canella R, Petrelli L, Marcolongo G, Leon A (1996) N-(2-hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation. Eur J Pharmacol 300:227–236

    Article  PubMed  CAS  Google Scholar 

  45. Calignano A, La Rana G, Giuffrida A, Piomelli D (1998) Control of pain initiation by endogenous cannabinoids. Nature 394:277–281

    Article  PubMed  CAS  Google Scholar 

  46. Jaggar SI, Hasnie FS, Sellaturay S, Rice AS (1998) The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain. Pain 76:189–199

    Article  PubMed  CAS  Google Scholar 

  47. Farquhar-Smith WP, Jaggar SI, Rice AS (2002) Attenuation of nerve growth factor-induced visceral hyperalgesia via cannabinoid CB(1) and CB(2)-like receptors. Pain 97:11–21

    Article  PubMed  CAS  Google Scholar 

  48. Farquhar-Smith WP, Rice AS (2001) Administration of endocannabinoids prevents a referred hyperalgesia associated with inflammation of the urinary bladder. Anesthesiology 94:507–513 (discussion 6A)

    Article  PubMed  CAS  Google Scholar 

  49. Ibrahim MM, Rude ML, Stagg NJ, Mata HP, Lai J, Vanderah TW, Porreca F, Buckley NE, Makriyannis A, Malan TP Jr (2006) CB2 cannabinoid receptor mediation of antinociception. Pain 122:36–42

    Article  PubMed  CAS  Google Scholar 

  50. Valenzano KJ, Tafesse L, Lee G, Harrison JE, Boulet JM, Gottshall SL, Mark L, Pearson MS, Miller W, Shan S, Rabadi L, Rotshteyn Y, Chaffer SM, Turchin PI, Elsemore DA, Toth M, Koetzner L, Whiteside GT (2005) Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology 48:658–672

    Article  PubMed  CAS  Google Scholar 

  51. Huffman JW, Liddle J, Yu S, Aung MM, Abood ME, Wiley JL, Martin BR (1999) 3-(1′,1′-Dimethylbutyl)-1-deoxy-delta8-THC and related compounds: synthesis of selective ligands for the CB2 receptor. Bioorg Med Chem 7:2905–2914

    Article  PubMed  CAS  Google Scholar 

  52. 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 20:2311–2320

    Article  PubMed  Google Scholar 

  53. Rinaldi-Carmona M, Barth F, Millan J, Derocq JM, Casellas P, Congy C, Oustric D, Sarran M, Bouaboula M, Calandra B, Portier M, Shire D, Breliere JC, Le Fur GL (1998) SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J Pharmacol Exp Ther 284:644–650

    PubMed  CAS  Google Scholar 

  54. Rinaldi-Carmona M, Barth F, Heaulme M, Alonso R, Shire D, Congy C, Soubrie P, Breliere JC, Le Fur G (1995) Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain cannabinoid receptor antagonist. Life Sci 56:1941–1947

    Article  PubMed  CAS  Google Scholar 

  55. Nackley AG, Makriyannis A, Hohmann AG (2003) Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation. Neuroscience 119:747–757

    Article  PubMed  CAS  Google Scholar 

  56. Whiteside GT, Gottshall SL, Boulet JM, Chaffer SM, Harrison JE, Pearson MS, Turchin PI, Mark L, Garrison AE, Valenzano KJ (2005) A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833. Eur J Pharmacol 528:65–72

    Article  PubMed  CAS  Google Scholar 

  57. Clayton N, Marshall FH, Bountra C, O’Shaughnessy CT (2002) CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain 96:253–260

    Article  PubMed  CAS  Google Scholar 

  58. Sanson M, Bueno L, Fioramonti J (2006) Involvement of cannabinoid receptors in inflammatory hypersensitivity to colonic distension in rats. Neurogastroenterol Motil 18:949–956

    Article  PubMed  CAS  Google Scholar 

  59. Jonsson KO, Persson E, Fowler CJ (2006) The cannabinoid CB2 receptor selective agonist JWH133 reduces mast cell oedema in response to compound 48/80 in vivo but not the release of beta-hexosaminidase from skin slices in vitro. Life Sci 78:598–606

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  61. Sokal DM, Elmes SJ, Kendall DA, Chapman V (2003) Intraplantar injection of anandamide inhibits mechanically-evoked responses of spinal neurones via activation of CB2 receptors in anaesthetised rats. Neuropharmacology 45:404–411

    Article  PubMed  CAS  Google Scholar 

  62. Guindon J, Desroches J, Beaulieu P (2007) The antinociceptive effects of intraplantar injections of 2-arachidonoyl glycerol are mediated by cannabinoid CB2 receptors. Br J Pharmacol 150:693–701

    Article  PubMed  CAS  Google Scholar 

  63. Jhaveri MD, Richardson D, Chapman V (2007) Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain. British Journal of Pharmacology, DOI 10.1038/sj.bjp.0707433

  64. Brennan TJ, Vandermeulen EP, Gebhart GF (1996) Characterization of a rat model of incisional pain. Pain 64:493–501

    Article  PubMed  CAS  Google Scholar 

  65. LaBuda CJ, Koblish M, Little PJ (2005) Cannabinoid CB2 receptor agonist activity in the hindpaw incision model of postoperative pain. Eur J Pharmacol 527:172–174

    Article  PubMed  CAS  Google Scholar 

  66. Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML (2005) Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 25:1904–1913

    Article  PubMed  CAS  Google Scholar 

  67. Benito C, Nunez E, Tolon RM, Carrier EJ, Rabano A, Hillard CJ, Romero J (2003) Cannabinoid CB2 receptors and fatty acid amide hydrolase are selectively overexpressed in neuritic plaque-associated glia in Alzheimer’s disease brains. J Neurosci 23:11136–11141

    PubMed  CAS  Google Scholar 

  68. Yiangou Y, Facer P, Durrenberger P, Chessell IP, Naylor A, Bountra C, Banati RR, Anand P (2006) COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol 6:12

    Article  PubMed  CAS  Google Scholar 

  69. Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN (2005) Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 95:437–445

    Article  PubMed  CAS  Google Scholar 

  70. Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O’Donnell D (2003) Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur J Neurosci 17:2750–2754

    Article  PubMed  Google Scholar 

  71. Scott DA, Wright CE, Angus JA (2004) Evidence that CB-1 and CB-2 cannabinoid receptors mediate antinociception in neuropathic pain in the rat. Pain 109:124–131

    Article  PubMed  CAS  Google Scholar 

  72. Ibrahim MM, Deng H, Zvonok A, Cockayne DA, Kwan J, Mata HP, Vanderah TW, Lai J, Porreca F, Makriyannis A, Malan TP Jr (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 100:10529–10533

    Article  PubMed  CAS  Google Scholar 

  73. Liu C, Walker JM (2006) Effects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain. J Neurophysiol 96:2984–2994

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  75. Patel HJ, Birrell MA, Crispino N, Hele DJ, Venkatesan P, Barnes PJ, Yacoub MH, Belvisi MG (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 140:261–268

    Article  PubMed  CAS  Google Scholar 

  76. Griffin G, Fernando SR, Ross RA, McKay NG, Ashford ML, Shire D, Huffman JW, Yu S, Lainton JA, Pertwee RG (1997) Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals. Eur J Pharmacol 339:53–61

    Article  PubMed  CAS  Google Scholar 

  77. Wieseler-Frank J, Maier SF, Watkins LR (2005) Central proinflammatory cytokines and pain enhancement. Neurosignals 14:166–174

    Article  PubMed  CAS  Google Scholar 

  78. Tanga FY, Raghavendra V, DeLeo JA (2004) Quantitative real-time RT-PCR assessment of spinal microglial and astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int 45:397–407

    Article  PubMed  CAS  Google Scholar 

  79. McMahon SB, Cafferty WB, Marchand F (2005) Immune and glial cell factors as pain mediators and modulators. Exp Neurol 192:444–462

    Article  PubMed  CAS  Google Scholar 

  80. Inoue A, Ikoma K, Morioka N, Kumagai K, Hashimoto T, Hide I, Nakata Y (1999) Interleukin-1beta induces substance P release from primary afferent neurons through the cyclooxygenase-2 system. J Neurochem 73:2206–2213

    PubMed  CAS  Google Scholar 

  81. Stella N (2004) Cannabinoid signaling in glial cells. Glia 48:267–277

    Article  PubMed  Google Scholar 

  82. Zhang DX, Owens CM, Willis WD (1991) Two forms of inhibition of spinothalamic tract neurons produced by stimulation of the periaqueductal gray and the cerebral cortex. J Neurophysiol 65:1567–1579

    PubMed  CAS  Google Scholar 

  83. Puffenbarger RA, Boothe AC, Cabral GA (2000) Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells. Glia 29:58–69

    Article  PubMed  CAS  Google Scholar 

  84. Ortega-Gutierrez S, Molina-Holgado E, Guaza C (2005) Effect of anandamide uptake inhibition in the production of nitric oxide and in the release of cytokines in astrocyte cultures. Glia 52:163–168

    Article  PubMed  Google Scholar 

  85. Elmes SJ, Winyard LA, Medhurst SJ, Clayton NM, Wilson AW, Kendall DA, Chapman V (2005) Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat. Pain 118:327–335

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We would like to thank Wellcome Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council and GlaxoSmithKline for financial support towards the original research presented in this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maulik D. Jhaveri.

Additional information

Jhaveri and Sagar joint first author.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jhaveri, M.D., Sagar, D.R., Elmes, S.J.R. et al. Cannabinoid CB2 Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain. Mol Neurobiol 36, 26–35 (2007). https://doi.org/10.1007/s12035-007-8007-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-007-8007-7

Keyword

Navigation