Prado Wiliam A, Faganello Fernanda A
Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
Pain. 2000 Nov;88(2):169-176. doi: 10.1016/S0304-3959(00)00326-2.
The anterior pretectal nucleus (APtN) and the dorsal raphe nucleus (DRN) are involved in descending pathways that control noxious inputs to the spinal cord and participate in the normal physiological response to noxious stimulation. Evidence has also been provided for the involvement of the APtN acting as a relay station through which the DRN partly modulates spinal nociceptive messages. In the present study, the effects of microinjecting glutamate or morphine into the DRN on the latency for the tail withdrawal reflex after noxious heating of the skin were examined in rats in which hyperbaric lidocaine (5%), naloxone (a non-selective opioid antagonist) or methiothepin (a non-selective 5-HT(1) antagonist) was previously microinjected into the APtN. Microinjection of glutamate (38 nmol/0.25 microl) into the DRN evoked strong but short-lasting antinociception that was fully inhibited by the previous administration of lidocaine (0.25 microl), naloxone (2.7 nmol/0.25 microl), or methiothepin (1 nmol/0.25 microl). A smaller dose of methiothepin (0.5 nmol/0.25 microl) significantly reduced the effect of glutamate. Microinjection of morphine (7.5 nmol/0.25 microl) into the DRN evoked strong and long-lasting antinociception that was not significantly changed by previous microinjection of lidocaine into the APtN. These results confirm that APtN integrity is at least in part necessary for the antinociceptive effects of stimulating the DRN, and that at least opioid and 5-HT1 mechanisms in the APtN participate as neuromodulators in the DRN-APtN connection. The results demonstrate that the antinociceptive effects of stimulating the DRN-APtN path depend on the activation of cell bodies in the DRN that can be excited by the local administration of glutamate, but not morphine. The study also further supports the notion that the DRN is involved in both descending and ascending pain inhibitory systems.
前顶盖前核（APtN）和中缝背核（DRN）参与下行通路，该通路控制脊髓的伤害性输入，并参与对伤害性刺激的正常生理反应。也有证据表明，APtN作为一个中继站参与其中，DRN通过该中继站部分调节脊髓伤害性信息。在本研究中，在预先将高压利多卡因（5%）、纳洛酮（一种非选择性阿片类拮抗剂）或甲硫噻平（一种非选择性5-HT(1)拮抗剂）微量注射到APtN的大鼠中，检测了向DRN微量注射谷氨酸或吗啡对皮肤有害加热后尾部撤离反射潜伏期的影响。向DRN微量注射谷氨酸（38 nmol/0.25微升）可诱发强烈但持续时间短的镇痛作用，而预先注射利多卡因（0.25微升）、纳洛酮（2.7 nmol/0.25微升）或甲硫噻平（1 nmol/0.25微升）可完全抑制该作用。较小剂量的甲硫噻平（0.5 nmol/0.25微升）可显著降低谷氨酸的作用。向DRN微量注射吗啡（7.5 nmol/0.25微升）可诱发强烈且持久的镇痛作用，预先向APtN微量注射利多卡因对此作用无显著影响。这些结果证实，APtN的完整性至少在一定程度上是刺激DRN产生镇痛作用所必需的，并且APtN中至少阿片类和5-HT1机制作为神经调节剂参与DRN-APtN连接。结果表明，刺激DRN-APtN通路的镇痛作用取决于DRN中细胞体的激活，这些细胞体可被局部注射谷氨酸而非吗啡所兴奋。该研究还进一步支持了DRN参与下行和上行疼痛抑制系统的观点。
