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CB 1 receptor antagonist SR141716A increases capsaicin‐evoked release of Substance P from the adult mouse spinal cord

Cannabinoids have an antinociceptive action in many pain models. We have investigated a possible modulatory role for Type 1 Cannabinoid receptors (CB 1 ) on the release of excitatory transmitter Substance P from the adult mouse spinal cord after stimulation of nociceptor terminals by capsaicin. Caps...

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Bibliographic Details
Published in:British journal of pharmacology 2009-01, Vol.135 (1), p.21-24
Main Authors: Lever, I J, Malcangio, M
Format: Article
Language:English
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Summary:Cannabinoids have an antinociceptive action in many pain models. We have investigated a possible modulatory role for Type 1 Cannabinoid receptors (CB 1 ) on the release of excitatory transmitter Substance P from the adult mouse spinal cord after stimulation of nociceptor terminals by capsaicin. Capsaicin (0.1 – 10 μ M ) was applied to superfused cord sections and evoked a dose dependent release of SP above basal outflow of (23.36±2.96 fmol 8 ml −1 ). Maximum evoked SP release was obtained with 5 μ M Capsaicin (262.4±20.8 fmol 8 ml −1 ). Higher capsaicin concentrations (50 – 100 μ M ) evoked less SP release. Superfusion of CB 1 antagonist SR141716A (5 μ M ) increased evoked SP release with capsaicin (0.1 – 10 μ M ) and reversed the reducing effect of high dose capsaicin (100 μ M ). Antagonism of CB 1 receptors in the spinal cord during capsaicin stimulation, is evidence of tonic CB 1 activity inhibiting the release of excitatory transmitters after activation of nociceptive neurones and is also indicative of endocannabinoid production during noxious stimulation. British Journal of Pharmacology (2002) 135 , 21–24; doi: 10.1038/sj.bjp.0704506
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704506