Effects of cannabinoids on capsaicin receptor activity following exposure of primary sensory neurons to inflammatory mediators

• Published in: Life sciences (1973) 2010-07, Vol.87 (5), p.162-168
• Main Authors: Soneji, Neil D., Paule, Cleoper C., Mlynarczyk, Marta, Nagy, Istvan
• Format: Article
• Language: English
• Subjects: Anandamide; Animals; Arachidonic Acids - administration & dosage; Arachidonic Acids - pharmacology; Bradykinin - metabolism; Capsaicin - administration & dosage; Capsaicin - pharmacology; CB1; Cells, Cultured; Cobalt - metabolism; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Dronabinol - administration & dosage; Dronabinol - analogs & derivatives; Dronabinol - pharmacology; Endocannabinoids; Inflammation Mediators - metabolism; Male; Nerve Growth Factor - metabolism; Nociception; Non-CB1/non-CB2; Pain; Polyunsaturated Alkamides - administration & dosage; Polyunsaturated Alkamides - pharmacology; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; Transient receptor potential vanilloid type 1 ion channel; TRPV Cation Channels - antagonists & inhibitors; TRPV1
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2010.06.003

Activation of the cannabinoid 1 (CB1) receptor in cultured primary sensory neurons reduces responses mediated through the transient receptor potential vanilloid type 1 receptor (TRPV1), which plays a pivotal role in the development of heat hyperalgesia and visceral hyper-reflexia in inflammatory conditions. Here, we studied the effect of cannabinoid-evoked inhibitory effect on TRPV1 in inflammatory conditions. The effect of anandamide (1 nM–30 nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (HU210; 1 μM–10 μM) was assessed on capsaicin (10 nM or 100 nM)-evoked cobalt uptake in rat cultured primary sensory neurons following the incubation of the cells in an “inflammatory environment” created by the major inflammatory mediators, bradykinin (5 μM), prostaglandin E 2 (5 μM) and nerve growth factor (100 ng/ml) for 10 min. 1 nM and 10 nM anandamide significantly reduced the 10 nM but not the 100 nM capsaicin-evoked responses. HU210 did not produce a significant change in responses evoked by capsaicin at either of its concentrations. The anandamide-induced inhibitory effect could not be reversed by the CB1 receptor antagonist, rimonabant (200 nM) or the membrane-permeable cAMP analogue, 8Br-cAMP (100 μM). These findings suggest that anandamide may inhibit TRPV1-mediated responses in a non-CB1/non-cannabinoid 2 receptor-dependent manner in primary sensory neurons in inflammatory conditions.