| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 99 === Neuropathic pain afflicts millions of people and is one of the most important health problems in the world. Mechanisms of nerve injury-induced neuropathic pain are incompletely known, which hinders effective management of this disabled pain condition.
Recently, evidences showed that peripheral nerve injury provokes complex immune response and glia activation at several different anatomical locations: peripheral nerve, dorsal root ganglion, and spinal dorsal horn. These responses promote inflammatory factor release, alter neuronal function in the peripheral and central nervous systems, and lead to neuropathic pain. Besides, injury discharge is followed by the onset of spontaneous activity, and this activity is strongly implicated in the generation of neuropathic pain. Local anesthetic is a nerve conduction blockade agent as well as an agent of attenuating activated glial cells when intrathecal supply. These effects lead to the interest in local anesthetic in the management of neuropathic pain. In addition, evidences showed that prevention or treatment at early stage of neuropathic pain might be important for the success.
We investigated the effect of preventive intrathecal bupivacaine in the chronic constriction injury (CCI) rat model of neuropathic pain. Male Sprague-Dawley rats were divided into four groups and three groups received intrathecal 25μl normal saline or 2.5mg/ml, 5.0mg/ml bupivacaine, respectively. Thirty minutes later, the rats received CCI surgery over left sciatic nerve. The fourth group received sham surgery. The behavioral change of mechanical allodynia tested by von Frey withdrawal test and thermal hyperalgesia tested by hot-plate test. For further investigating the possible mechanisms, the rats sacrificed on the post-operative day 7. The spinal cord and sciatic nerve tissue examined and analyzed by immune cell infiltration in spinal cord and dorsal root ganglion will be examined by immunohistochemistry, Western blot and RTPCR.
The results showed that, compared with control group, there was significant increase in mechanical threshold at injured limb in both treatment groups on the post-operative day 3, 5 and 7. There was also significant decrease thermal hyperalgesia in 2.5mg/ml and 5.0mg/ml group on the post-operative day 7 and day 14, respectively. There were decreasing microglia and astrocyte activation as well as decreasing the production of IL-1β, IL-6, p-IκB-α and COX-2 in the ipsilateral of spinal dorsal horn in both treatment groups. The results also showed decreased immune cell infiltration and Schwann cell proliferation as well as decreased the production of TNF-α, IL-1β, IL-6, MyD88, p-IκB-α and RANTES in the ipsilateral sciatic nerve in both treatment groups. In addition, TLR2 and TLR5 were decreased in the ipsilateral sciatic nerve in both treatment groups. There was no significant different results between two examed dosage in this study.
This study demonstrated preventive single dose intrathecal bupivacaine 30 minutes prior CCI surgery can decrease microglia, astrocyte and Schwann cell activation as well as decrease inflammatory response in spinal dorsal horn and sciatic nerve, and finally decrease the symptoms of neuropathic pain.
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