Suppression of neurokinin-1 receptor in trigeminal ganglia attenuates central sensitization following inflammation.
This study examined whether local application of a neurokinin-1 (NK1) receptor antagonist into the trigeminal ganglia (TRGs) modulates hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) wide-dynamic range (WDR) neuron activity innervating both the temporomandibular joint (TMJ) region and facial skin following TMJ inflammation. Extracellular single unit recording combined with multibarrel electrodes was used. TMJ inflammation was induced by the injection of complete Freund's adjuvant (CFA). WDR neurons responding to electrical stimuli of the TMJ region and facial skin were recorded from the SpVc in anesthetized rats. The spontaneous and mechanical stimulation-induced discharge frequencies of WDR neurons were significantly larger in inflamed rats than in control rats. The spontaneous WDR activities were current-dependently decreased by local iontophoretic application of an NK1 receptor antagonist into the TRGs after 1 and 2 days of inflammation. The firing frequency of WDR neurons and threshold evoked by mechanical stimulation of facial skin returned to control levels by application of the NK1 receptor antagonist into TRGs after 1 day, but not 2 days, of inflammation. These results suggest that in the early stages of inflammation suppression of the NK1 receptor mechanism in TRGs may prevent central sensitization of SpVc nociceptive neurons.
Department of Physiology, School of Life Dentistry at Tokyo, Nippon Dental University, Tokyo, Japan. m-takeda@tokyo.ndu.ac.jp
Mamoru
M
Takeda
Masayuki
M
Takahashi
Shigeji
S
Matsumoto
D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D059333:Central Nervous System Sensitization / Q000502:physiology*; D004594:Electrophysiology; D005145:Face / Q000294:innervation; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013704:Temporomandibular Joint / Q000187:drug effects; D013705:Temporomandibular Joint Disorders / Q000378:metabolism / Q000503:physiopathology; D012668:Trigeminal Ganglion / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018040:Receptors, Neurokinin-1; D005620:Freund's Adjuvant