Pan H L, Chen S R, Eisenach J C
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.
Anesthesiology. 1998 Dec;89(6):1518-23. doi: 10.1097/00000542-199812000-00031.
The role of spinal nitric oxide (NO) in neuropathic pain remains uncertain. Although intrathecal clonidine causes NO release in the spinal cord, the functional role of spinal NO in clonidine-produced analgesia has not been examined. The objectives of this study were to assess the role of spinal NO in maintenance of allodynia and to determine the role of spinal NO in the antiallodynic effect of intrathecal clonidine.
Allodynia was produced in rats by tight ligation of the left L5-L6 spinal nerves. Intrathecal catheters were inserted with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the left hindpaw. In the first series of experiments, allodynia was assessed before and after intrathecal injection of saline, L-arginine, an NO donor (SNAP), two NO synthase inhibitors (TRIM and NMMA), or an NO scavenger (PTIO). In the second series of experiments, 20 microg of clonidine was injected intrathecally 15 min after intrathecal injection of saline, TRIM, NMMA, or PTIO.
Allodynia was not affected significantly by intrathecal injection of L-arginine, SNAP, TRIM, NMMA, or PTIO. The antiallodynic effect produced by intrathecal injection of clonidine was attenuated significantly by pretreatment with TRIM, NMMA, or PTIO.
These results demonstrate that spinal NO neither contributes significantly to maintenance of allodynia nor produces detectable antiallodynic effect in this neuropathic pain model. Furthermore, this study provides functional evidence that spinal NO plays an important role in the antiallodynic effect of intrathecal clonidine in neuropathic pain.
脊髓一氧化氮（NO）在神经性疼痛中的作用仍不明确。尽管鞘内注射可乐定可导致脊髓释放NO，但脊髓NO在可乐定产生镇痛作用中的功能作用尚未得到研究。本研究的目的是评估脊髓NO在痛觉过敏维持中的作用，并确定脊髓NO在鞘内注射可乐定的抗痛觉过敏作用中的作用。
通过紧密结扎大鼠左侧L5-L6脊神经制造痛觉过敏。将鞘内导管插入至腰段鞘内间隙。通过将von Frey细丝应用于左后爪来测定机械性痛觉过敏。在第一组实验中，在鞘内注射生理盐水、L-精氨酸、一种NO供体（SNAP）、两种NO合酶抑制剂（TRIM和NMMA）或一种NO清除剂（PTIO）之前和之后评估痛觉过敏。在第二组实验中，在鞘内注射生理盐水、TRIM、NMMA或PTIO 15分钟后鞘内注射20μg可乐定。
鞘内注射L-精氨酸、SNAP、TRIM、NMMA或PTIO对痛觉过敏无显著影响。鞘内注射可乐定产生的抗痛觉过敏作用在经TRIM、NMMA或PTIO预处理后显著减弱。
这些结果表明，在该神经性疼痛模型中，脊髓NO对痛觉过敏的维持没有显著贡献，也没有产生可检测到的抗痛觉过敏作用。此外，本研究提供了功能证据，表明脊髓NO在鞘内注射可乐定对神经性疼痛的抗痛觉过敏作用中起重要作用。
