INVOLVEMENT OF INCREASED EXCITATORY AMINO-ACIDS AND INTRACELLULAR CA2-MODEL OF NEUROPATHIC PAIN( CONCENTRATION IN THE SPINAL DORSAL HORN INAN ANIMAL)

Neuropathic pain following nerve injury is believed to involve excitat ory amino acids (EAAs) and Ca2+-mediated neuronal plastic changes in t he central nervous system (CNS). This study was designed to investigat e the changes in glutamate and aspartate contents in the dorsal half o f the spinal cord following chronic constrictive injury (CCI) of the r at common sciatic nerve. We also examined the changes in intracellular calcium ion concentration ([Ca2+](i)) of the spinal dorsal horn in tr ansverse spinal slices in the same animal model. Thermal and mechanica l hyperalgesia were observed on day 2 and thereafter following CCI (P < 0.0001). In the CCI rats to which 0.5 mg/kg of i.p. MK-801 was given 30 min prior to CCI and subsequently three daily treatments with 0.5 mg/kg of i.p. MK-801, the development of thermal and mechanical hypera lgesia was suppressed for a period of up to 7 days; however, hyperalge sia appeared on day IO and day 14 (P < 0.001). In CCI rats, significan t increases were observed in glutamate and aspartate contents on the i psilateral side of the dorsal horn to nerve ligation on days 4, 7 and 14 (P < 0.001). Moreover, significant increases in [Ca2+](i) in the sp inal dorsal horn were also observed in the superficial (lamina I-II) a nd deep layers (lamina V-VI) on the ipsilateral side to nerve ligation on days 4, 7 and 14 after nerve ligation in the spinal slices (P < 0. 0001). The treatment with i.p. MK-801 suppressed the increases in the contents of glutamate and aspartate and in [Ca2+](i) on days 4 and 7. However, the ipsilateral contents of glutamate and aspartate significa ntly increased on day 14 (P < 0.001 and 0.003, respectively); the incr eased [Ca2+](i) was also observed on day 14 (P < 0.001), and the spati al pattern of the increased regions was similar to untreated CCI rats. We interpret these results to indicate that neuropathic hyperalgesia induced by CCI in the rat is associated with an increase in glutamate and aspartate contents and the subsequent activation of NMDA receptors , followed by an increase in [Ca2+](i) within dorsal horn of the spina l cord.