The anti-hyperalgesic actions of the cannabinoid anandamide and the putative CB2 receptor agonist palmitoylethanolamide in visceral and somatic inflammatory pain.
This study assessed the effects of two N-acylethanolamides in established rat models of visceral and somatic inflammatory pain. (1) The therapeutic effects of the cannabinoid anandamide and the putative CB2 agonist palmitoylethanolamide were tested in a model of persistent visceral pain (turpentine inflammation of the urinary bladder). Both anandamide (at a dose of 25 mg/kg) and palmitoylethanolamide (at doses of 10-30 mg/kg) were able to attenuate the viscero-visceral hyper-reflexia (VVH) induced by inflammation of the urinary bladder. (2) The effects of the same compounds on the behavioural response to subcutaneous formalin injection were assessed. The characteristic biphasic response was observed in control animals. Anandamide (dose range 5-25 mg/kg) and palmitoylethanolamide (dose range 5-10 mg/kg) both reduced the second phase of the response. The results confirm the analgesic potential of endogenous ligands at cannabinoid receptor sites. The anti-nociceptive effect of the putative CB2 receptor agonist, palmitoylethanolamide, is particularly interesting since it is believed to be a peripherally mediated effect. This observation might be exploited to separate central psychotropic effects from peripheral analgesic actions of the cannabinoids, under inflammatory conditions.
Department of Anaesthetics, Imperial College School of Medicine, St. Mary's Hospital, London, UK.
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Jaggar
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Hasnie
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D000577:Amides; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use*; D002186:Cannabinoids / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000187:drug effects; D003556:Cystitis / Q000473:pathology / Q000503:physiopathology; D004594:Electrophysiology; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D005557:Formaldehyde; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects; D010169:Palmitic Acids / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D001743:Urinary Bladder / Q000294:innervation / Q000473:pathology / Q000503:physiopathology
D000577:Amides; D000700:Analgesics; D001095:Arachidonic Acids; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D004983:Ethanolamines; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D005557:Formaldehyde; C005958:palmidrol; C078814:anandamide