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

鞘内注射NMDA受体拮抗剂APV（1 - 30 nmol）、非NMDA受体拮抗剂CNQX（1 - 30 nmol）和NK-1受体拮抗剂CP-96，345（0.3 - 10 nmol），均可抑制吗啡诱导的大鼠炎性痛觉过敏。鞘内注射NMDA（1 nmol）和AMPA（1 nmol）引起的厌恶行为在佐剂性炎症下增加，而P物质（1 nmol）则无此作用。鞘内注射APV（1 - 30 nmol）、CNQX（1 - 30 nmol）、CP-96，345（0.3 - 10 nmol）和抗P物质抗体，可抑制冷应激引起的大鼠痛觉过敏。重复冷应激增加了鞘内注射NMDA（1 nmol）和AMPA（1 nmol）引起的厌恶行为。P物质（1 nmol）引起的行为反应有增加或增加的趋势。原位杂交分析NMDAR 1 mRNA和NK-1 mRNA在腰椎背角或大鼠中的分布没有显示佐剂接种明显增加其表达。这些结果表明，谷氨酸和P物质介导的突触传递的易化是负责由佐剂炎症和反复冷应激诱导的痛觉过敏。然而，本研究结果并不支持镇痛药引起的痛觉过敏是由于脊髓背角NMDAR 1和NK-1受体生物合成增加的观点。

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.