Blockade of capsaicin-induced reduction of GABA-immunoreactivity by spantide in cat spinal superficial dorsal horn.
In our previous study, perineural application of capsaicin not only produced release and depletion of substance P from primary nociceptive afferent terminals, but also reduced GABA immunoreactivity in the superficial dorsal horn. The aim of the present study was to determine whether the release of GABA is triggered by substance P released from primary nociceptive afferent terminals by capsaican. GABA and substance P immunoreactivity in the lumbar dorsal horn was examined in two groups: in the first group the tibial nerve was treated with 3% capsaicin, and in the second group the dorsal surface of the lumbar cord was infused with spantide (50 nM), a substance P receptor antagonist, before application of capsaicin to the tibial nerve. Following perineural treatment of capsaicin for 30 min, both the GABA-immunostaining density and the number of GABA immunoreactive neurons were reduced significantly in the ipsilateral laminae I-II at L5 through L7. GABA immunoreactivity was reduced by 54.12%, 44.46% and 31.0% in the medial, central and lateral parts of the ipsilateral laminae I-II at L7, respectively. With pre-application of spantide to the spinal cord, GABA immunoreactivity was reduced only to 14.4%, 16.4% and 10.16%, respectively, in the medial, central and lateral parts of laminae I-II at L7 and no reduction of GABA immunoreactive neurons was observed. Additionally, capsaicin-induced reduction of substance P immunoreactivity was partially blocked by spantide. These results suggest that capsaicin produces substance P release from primary nociceptive afferent terminals, and that substance P, in turn, activates the second-order GABAergic interneurons in the dorsal horn. The functional significance of capsaicin-induced activation of GABAergic neurons in modulation of spinal nociception is discussed.
Wei
F
F
Shanghai Brain Research Institute, Chinese Academy of Sciences.
Zhao
Z Q
ZQ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002415:Cats; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000700:Analgesics; D013373:Substance P; D005680:gamma-Aminobutyric Acid; C042867:spantide; D002211:Capsaicin