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

通过鞘内注射NMDA拮抗剂APV （1 ~ 30 nmol）、非NMDA拮抗剂CNQX （1 ~ 30 nmol）和NK-1拮抗剂CP-96,345 (0.3 ~ 10 nmol)，可以抑制佐剂诱导的大鼠炎症性痛觉过敏。在辅助炎症下，鞘内注射NMDA （1 nmol）和AMPA （1 nmol）引起的厌恶行为增加，但P物质（1 nmol）没有增加。经鞘内注射APV （1 ~ 30 nmol）、CNQX （1 ~ 30 nmol）、CP-96,345 （0.3 ~ 10 nmol）和抗P物质抗体，可抑制重复冷应激引起的大鼠痛觉过敏。重复冷应激增加鞘内注射NMDA （1 nmol）和AMPA （1 nmol）引起的厌恶行为。P物质（1nmol）诱导的行为反应有增加或增加的趋势。原位杂交分析NMDAR1 mRNA和NK-1 mRNA在大鼠腰椎背角和大鼠腰背角的分布，未发现佐剂接种后其表达明显增加。这些结果表明，促进谷氨酰胺和p物质介导的突触传递是佐剂炎症和反复冷应激引起的痛觉过敏的原因。然而，目前的结果并不支持佐剂诱导的痛觉过敏是由于脊髓背角中NMDAR1和NK-1受体的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.