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


METHODS
The effect of anandamide (1 nM-30 nM) and 1,1-dimethylheptyl-11-hydroxytetrahydrocannabinol (HU210; 1 microM-10 microM) 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 microM), prostaglandin E(2) (5 microM) and nerve growth factor (100 ng/ml) for 10 min.


RESULTS
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 microM).


CONCLUSIONS
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.
Soneji
Neil D
ND
Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom.
Paule
Cleoper C
CC
Mlynarczyk
Marta
M
Nagy
Istvan
I
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D003035:Cobalt / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D063388:Endocannabinoids; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; D063388:Endocannabinoids; D018836:Inflammation Mediators; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D003035:Cobalt; D013759:Dronabinol; D020932:Nerve Growth Factor; D015232:Dinoprostone; C062018:HU 211; D002211:Capsaicin; D001920:Bradykinin; C078814:anandamide