The present studies were conducted to test the hypothesis that systemically inactive doses of
cannabinoids suppress
inflammation-evoked neuronal activity in vivo via a peripheral mechanism. We examined peripheral
cannabinoid modulation of spinal Fos
protein expression, a marker of neuronal activity, in a rat model of
inflammation. Rats received unilateral intraplantar
injections of
carrageenan (3%). In behavioral studies,
carrageenan induced
allodynia and
mechanical hyperalgesia in response to stimulation with von Frey monofilaments. The
cannabinoid agonist WIN55,212-2 (30 microg intraplantarly), administered concurrently with
carrageenan, attenuated
carrageenan-evoked
allodynia and
hyperalgesia relative to control conditions. In immunocytochemical studies, WIN55,212-2 suppressed the development of
carrageenan-evoked Fos
protein expression in the lumbar dorsal horn of the spinal cord relative to vehicle treatment. The same dose administered systemically or to the noninflamed contralateral paw failed to alter either
carrageenan-evoked
allodynia and
hyperalgesia or
carrageenan-evoked Fos
protein expression, consistent with a peripheral site of action. The suppressive effects of WIN55,212-2 (30 microg intraplantarly) on
carrageenan-evoked Fos
protein expression and
pain behavior were blocked by local administration of either the CB(2) antagonist
SR144528 (30 microg intraplantarly) or the CB(1) antagonist
SR141716A (100 microg intraplantarly). WIN55,212-3, the enantiomer of the active compound, also failed to suppress
carrageenan-evoked Fos
protein expression. These data provide direct evidence that a peripheral
cannabinoid mechanism suppresses the development of
inflammation-evoked neuronal activity at the level of the spinal dorsal horn and implicate a role for CB(2) and CB(1) in peripheral
cannabinoid modulation of inflammatory nociception.