Change of glutamate and tachykinin receptors in chronic pain model animals (molecular biological and pharmacological study)

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The adjuvant-induced inflammatory hyperalgesia of the rat was inhibited by an intrathecal injection of the NMDA antagonist APV (1 - 30 nmol), the non-NMDA antagonist CNQX (1 - 30 nmol), and the NK-1 antagonist CP-96,345 (0.3 - 10 nmol). Aversive behaviors elicited by an intrathecal injection of NMDA (1 nmol) and AMPA (1 nmol), but not substance P (1 nmol), were increased Under adjuvant inflammation. The byperalgesia of the rat induced by repeated cold stress was suppressed by an intrathecal injection of APV (1 - 30 nmol), CNQX (1 - 30 nmol), CP-96,345 (0.3 - 10 nmol), and anti-substance P antibody. Repeated cold stress increased aversive behaviors elicited by an intrathecal injection of NMDA (1 nmol) and AMPA (1 nmol). There was an increase or increased tendency in behavioral response induced by substance P (1 nmol). In situ hybridization analysis of the distribution of NMDAR1 mRNA and NK-1 mRNA in the lumbar dorsal horn or the rat did not show the apparent increase in their expression by adjuvant inoculation. These results suggest that facilitation of glutamergic and substance P-mediated synaptic transmission is responsible for the hyperalgesia induced by adjuvant inflammation and repeated cold stress. However, the present results does not support the idea that adjuvant-induced hyperalgesia is due to the increased biosyntheis of NMDAR1 and NK-1 receptors in the spinal dorsal horn.