Group 1 Meatabotropic Glutamate Receptor Agonist Excites Capsaicin-sensitive Primary Afferent Fiber in the Rat

초록

Group 1 metabotropic glutamate receptor (mGluR) is expressed both in the spinal cord and peripheral nerve, and is involved in nociceptive responses induced by intrathecal or peripheral injection of group 1 mGluR agonists. Group 1 mGluR has been reported to activate phospholipase C which results in the increase in IP3 formation, Ca2+ influx and protein kinase C activity. This study undertaken to investigate how much portion of peripherally administered group 1 mGluR-induced nociceptive responses was mediated by the activation of capsaicin-sensitive afferent fibers. Changes in group 1 mGluR agonist- and mGluR5 agonist-induced mechanical threshold,spontaneous flinching and paw thickness were measured in the control and capsaicin-treated rat and compared each other. Capsaicin (1%) was applied to sciatic nerve at the mid-thigh level about 24hr before testing. Intraplantar injection of group 1 mGluR agonist ((RS)-3,5-dihydroxyphenylglycine, DHPG, 40ug & 80ug/paw) and mGluR5 agonist ((RS)-2-chloro-5-hydroxyphenyglycine, CHPG, 20ug & 40ug/paw) caused a sustained decrease in mechanical threshold and an increase in spontaneous flinching, but did not have any significant effect on paw thickness. Capsaicin pretreatment significantly reduced the decrease in mechanical threshold induced by CHPG (40ug/paw) at all time points after CHPG injection. However, DHPG-induced (80ug/paw) decrease in mechanical threshold was significantly attenuated in capsaicin-treated rat during the inital 30 min after DHPG injection. Capsaicin-pretreatment also reduced the increase in flinchings induced by DHPG and CHPG. The results obtained from the present study suggest that greater portion of group 1 mGluR-induced nociceptive responses are mediated through capsaicin-sensitive primary afferent activation.