Inhibition of noxious stimulus-evoked activity of spinal cord dorsal horn neurons by the cannabinoid WIN 55,212-2.
The effects of a potent synthetic cannabinoid WIN 55,212-2 on nociceptive responses of wide dynamic range (WDR) neurons in the lumbar spinal cord were investigated in anesthetized rats. WDR neurons were identified by their responses to innocuous brushing and to a range of pressure stimuli from innocuous to noxious. Noxious pressure was applied to regions of the ipsilateral hind paw corresponding to the receptive field of the neuron. WIN 55,212-2 (125 micrograms/kg and 250 micrograms/kg, i.v.) produced a profound inhibition of firing evoked by the noxious pressure stimulus. By contrast, the cannabinoid did not alter the evoked activity of non-nociceptive neurons in response to non-noxious levels of stimulation. Treatment with either vehicle or the inactive enantiomer WIN 55,212-3 (250 micrograms/kg) failed to alter noxious stimulus-evoked activity of WDR neurons. These data provide direct evidence for cannabinoid-mediated inhibition of pain neurotransmission in the spinal dorsal horn. The site of action for these effects remains to be determined.
Hohmann
A G
AG
Schrier Research Laboratory, Department of Psychology, Brown University, Providence, RI, USA.
Martin
W J
WJ
Tsou
K
K
Walker
J M
JM
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D048588:Benzoxazines; D005071:Evoked Potentials; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone