Skyba D A, King E W, Sluka Kathleen A
Neuroscience Graduate Program, University of Iowa, Iowa City, IA 52242, USA.
Pain. 2002 Jul;98(1-2):69-78. doi: 10.1016/s0304-3959(01)00471-7.
Two unilateral injections of pH 4.0 saline into the gastrocnemius muscle result in a bilateral decrease in mechanical withdrawal threshold after the second injection. This decrease is significant by 4h and lasts through 1 week. The purpose of this study was to characterize the involvement of both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal cord dorsal horn in the development and maintenance of mechanical hyperalgesia from repeated intramuscular injections of acidic saline. 2-amino-5-phosphonovaleric acid (AP5) (2-20 nmol, 10 microl, pH 7) or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo[f]quinoxaline-7-sulfonamide (NBQX) (1-10 nmol, 10 microl, pH 8-9) was administered intrathecally to the lumbar spinal cord to block NMDA and non-NMDA ionotropic glutamate receptors in the dorsal horn, respectively. Drugs were administered at one of three different time points: (1) prior to the first intramuscular injection of pH 4.0 saline on Day 0, (2) prior to the second intramuscular injection of pH 4.0 saline on Day 5, and (3) 1 week after the second injection. Mechanical withdrawal thresholds were measured with von Frey filaments before, 4h, and 24h after injection 1 and before, 4h, 24h, and 1 week after injection 2. AP5 had no effect on mechanical withdrawal thresholds when administered prior to the first intramuscular injection of pH 4.0 saline. When AP5 was administered before the second intramuscular injection, the bilateral decrease in mechanical withdrawal thresholds was delayed for up to 24h. Intrathecal administration of AP5 1 week after the second intramuscular injection of pH 4.0 saline produced a bilateral increase in mechanical withdrawal thresholds. Blockade of non-NMDA glutamate receptors in the spinal cord dorsal horn prior to either the first or second intramuscular injection of pH 4.0 saline had no effect on the development of mechanical hyperalgesia. However, spinal injection of NBQX 1 week after the second intramuscular injection of pH 4.0 saline resulted in an increase in mechanical withdrawal thresholds when compared to vehicle controls. These data suggest that both NMDA and non-NMDA glutamate receptors are involved in the maintenance of chronic, muscle-induced hyperalgesia.
向腓肠肌单侧注射两次pH 4.0的生理盐水，在第二次注射后会导致双侧机械性退缩阈值降低。这种降低在4小时时显著，并持续1周。本研究的目的是确定N-甲基-D-天冬氨酸（NMDA）和非NMDA谷氨酸受体在脊髓背角参与重复肌肉注射酸性生理盐水所致机械性痛觉过敏的发生和维持过程中的作用。鞘内注射2-氨基-5-磷酸戊酸（AP5）（2-20 nmol，10微升，pH 7）或1,2,3,4-四氢-6-硝基-2,3-二氧代[f]喹喔啉-7-磺酰胺（NBQX）（1-10 nmol，10微升，pH 8-9），分别阻断背角的NMDA和非NMDA离子型谷氨酸受体。药物在三个不同时间点之一给药：（1）在第0天首次肌肉注射pH 4.0生理盐水之前，（2）在第5天第二次肌肉注射pH 4.0生理盐水之前，以及（3）第二次注射后1周。在注射1之前、注射后4小时和24小时以及注射2之前、注射后4小时、24小时和1周，用von Frey细丝测量机械性退缩阈值。在首次肌肉注射pH 4.0生理盐水之前给予AP5，对机械性退缩阈值没有影响。当在第二次肌肉注射之前给予AP5时，机械性退缩阈值的双侧降低延迟长达24小时。在第二次肌肉注射pH 4.0生理盐水1周后鞘内注射AP5，导致机械性退缩阈值双侧升高。在首次或第二次肌肉注射pH 4.0生理盐水之前阻断脊髓背角的非NMDA谷氨酸受体，对机械性痛觉过敏的发生没有影响。然而，在第二次肌肉注射pH 4.0生理盐水1周后脊髓注射NBQX，与溶剂对照组相比，导致机械性退缩阈值升高。这些数据表明，NMDA和非NMDA谷氨酸受体均参与慢性肌肉诱导的痛觉过敏的维持。
