Capsazepine, a novel capsaicin antagonist, selectively antagonises the effects of capsaicin in the mouse spinal cord in vitro.
The mouse hemisected spinal cord with attached dorsal roots and spinal ganglia in vitro preparation was used to investigate the effects of the capsaicin antagonist, capsazepine (2-[2-(4-chlorophenyl)ethylamino-thiocarbonyl]-7,8-dihydroxy-2,3,4 ,5- tetrahydro-1H-2-benzazepine). The spinal cord and the ganglia were separated by a perspex gap, allowing application of drugs separately to each compartment. Intracellular recordings were made from 37 cells in laminae II-VI of 12 to 20-day-old mice. Brief applications (30 s) of capsaicin (0.8 microM) excited dorsal horn neurones by activating small diameter primary afferent fibres. The response to capsaicin administered to the spinal cord or to the spinal ganglia was antagonised by the capsaicin antagonist, capsazepine (1.5 microM), administered to the same site. Excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of the dorsal root were not affected by capsazepine. Capsazepine itself (5 microM) did not affect the membrane potential of the dorsal horn cells. Capsazepine did not depress the depolarization evoked by substance P. When capsazepine was applied to the spinal cord and capsaicin to the dorsal root ganglion the capsaicin effect was not antagonised. These data suggest that capsaicin-induced depolarization of spinal dorsal horn neurones was mediated via activation of a specific receptor on primary afferent neurones.
Urban
L
L
Sandoz Institute for Medical Research, London, U.K.
Dray
A
A
D000200:Action Potentials / Q000187:drug effects; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000187:drug effects; D051379:Mice; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology
D011955:Receptors, Drug; D013373:Substance P; C071423:capsazepine; D002211:Capsaicin