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Activation of peripheral cannabinoid CB 1 receptors inhibits mechanically evoked responses of spinal neurons in noninflamed rats and rats with hindpaw inflammation
Author(s) -
Kelly Sara,
Jhaveri Maulik D.,
Sagar Devi R.,
Kendall David A.,
Chapman Victoria
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02957.x
Subject(s) - cannabinoid receptor , peripheral , inflammation , receptor , spinal cord , noxious stimulus , endocannabinoid system , agonist , am251 , medicine , cannabinoid , inhibitory postsynaptic potential , endocrinology , pharmacology , chemistry , nociception , psychiatry
The presence of cannabinoid 1 (CB 1 ) receptors on primary afferent fibres may provide a novel target for cannabinoid analgesics. The present study investigated the ability of peripheral CB 1 receptors to modulate innocuous and noxious transmission in noninflamed rats and rats with peripheral carrageenan inflammation. Effects of peripheral injection of arachidonyl‐2‐choroethylamide (ACEA; 10 and 30 µg in 50 µL), a selective CB 1 receptor agonist, on mechanically evoked responses of dorsal horn neurons were studied in noninflamed rats and rats with peripheral carrageenan inflammation. Peripheral injection of ACEA (30 µg in 50 µL) significantly inhibited innocuous (12 g) mechanically evoked responses of spinal neurons in noninflamed (27 ± 4% of control; P < 0.01) and inflamed (12 ± 8% of control; P < 0.05) rats. Similarly, noxious (80 g) mechanically evoked responses of spinal neurons were inhibited by peripheral injection of ACEA (30 µg in 50 µL) in noninflamed rats (51 ± 9% of control; P < 0.01) and rats with peripheral carrageenan inflammation (21 ± 8% of control; P < 0.01). Inhibitory effects of ACEA were significantly greater in rats with peripheral carrageenan inflammation than in noninflamed rats ( P < 0.05). Inhibitory effects of ACEA were significantly blocked by coadministration of the CB 1 receptor antagonist SR141716A in both groups of rats. Peripheral injection of SR141716A alone did not alter mechanically evoked responses of spinal neurons in either group of rats. These data demonstrate that activation of peripheral CB 1 receptors can inhibit innocuous and noxious somatosensory processing. Furthermore, following peripheral inflammation there is an enhanced inhibitory effect of a peripherally administered CB 1 receptor agonist on both innocuous and noxious mechanically evoked responses of spinal neurons.