Zahn P K, Umali E, Brennan T J
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242-1079, USA.
Pain. 1998 Feb;74(2-3):213-23. doi: 10.1016/s0304-3959(97)00181-4.
Evidence indicates that excitatory amino acids (EAAs) like glutamate and aspartate are important in the processing of nociceptive information in the dorsal horn of the spinal cord. Recently, the role of particular EAA receptors in pain transmission and facilitated pain states has been examined utilizing spinal administration of specific receptor antagonists. Most investigators have studied the involvement of N-methyl-D-aspartate (NMDA) EAA receptors in hyperalgesia and nociception; less is known about the importance of non-NMDA EAA receptors in animal models of persistent pain. To study the role of spinal non-NMDA EAA receptors in pain behaviors caused by an incision, we examined the effect of i.t. administered non-NMDA EAA receptor antagonists in a rat model of postoperative pain. Rats with i.t. catheters were anesthetized and underwent a plantar incision. Withdrawal threshold to punctate stimulation applied adjacent to the wound using von Frey filaments, response frequency to application of a non-punctate stimulus applied directly to the wound and non-evoked pain behaviors were measured before and after administration of i.t. 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo[f]quinoxaline-7-sulfonamide (NBQX), 6,7-dinitroquinoxaline-2,3-dione (DNQX), or vehicle. A separate group of animals were also tested for motor impairment caused by these drugs. In the vehicle-treated group, the median withdrawal threshold for punctate hyperalgesia decreased from 522 mN before surgery to 39 mN 2 h later; hyperalgesia was persistent. Intrathecal administration of 5 or 10 nmol of NBQX returned the withdrawal threshold toward preincision values; the median withdrawal thresholds were 158 and 360 mN, respectively. Intrathecal administration of 10 nmol of DNQX similarly increased the withdrawal threshold after incision. In separate groups of animals, i.t. administration of 5 or 10 nmol of NBQX decreased the response frequency to a non-punctate stimulus applied directly to the incision from 100+/-0% 2 h after surgery to 22+/-11 and 0+/-0% 30 min after drug injection, respectively. Similar results were observed with i.t. administration of 10 nmol of DNQX. Intrathecal NBQX also inhibited non-evoked pain behavior. In conclusion, non-NMDA receptor antagonists produced a marked decrease in pain behaviors in this model of postoperative pain. Thus, non-NMDA receptors are important for the maintenance of short-term pain behaviors caused by an incision and drugs blocking these receptors may be useful for the treatment of postoperative pain in patients.
有证据表明，谷氨酸和天冬氨酸等兴奋性氨基酸（EAAs）在脊髓背角伤害性信息的处理过程中发挥着重要作用。最近，通过向脊髓给药特定受体拮抗剂，研究了特定EAA受体在疼痛传递和疼痛易化状态中的作用。大多数研究人员研究了N-甲基-D-天冬氨酸（NMDA）EAA受体在痛觉过敏和伤害感受中的作用；而对于非NMDA EAA受体在持续性疼痛动物模型中的重要性了解较少。为了研究脊髓非NMDA EAA受体在切口引起的疼痛行为中的作用，我们在大鼠术后疼痛模型中检测了鞘内注射非NMDA EAA受体拮抗剂的效果。对植入鞘内导管的大鼠进行麻醉并在足底做切口。在鞘内注射1,2,3,4-四氢-6-硝基-2,3-二氧代[f]喹喔啉-7-磺酰胺（NBQX）、6,7-二硝基喹喔啉-2,3-二酮（DNQX）或赋形剂前后，使用von Frey细丝测量伤口附近点状刺激的撤针阈值、直接施加于伤口的非点状刺激的反应频率以及非诱发性疼痛行为。还对另一组动物测试了这些药物引起的运动障碍。在赋形剂处理组中，点状痛觉过敏的撤针阈值中位数从手术前的522 mN降至术后2小时的39 mN；痛觉过敏持续存在。鞘内注射5或10 nmol的NBQX可使撤针阈值恢复至切口前水平；中位数撤针阈值分别为158和360 mN。鞘内注射10 nmol的DNQX同样可提高切口后的撤针阈值。在另一组动物中，鞘内注射5或10 nmol的NBQX可使直接施加于切口的非点状刺激的反应频率分别从术后2小时的100±0%降至药物注射后30分钟的22±11%和0±0%。鞘内注射10 nmol的DNQX也观察到类似结果。鞘内注射NBQX还可抑制非诱发性疼痛行为。总之，在该术后疼痛模型中，非NMDA受体拮抗剂可显著减轻疼痛行为。因此，非NMDA受体对于维持切口引起的短期疼痛行为很重要，阻断这些受体的药物可能对治疗患者的术后疼痛有用。
