Mediators of Neuroinflammation In Rat Neuropathic Pain Model
Project no. 167 · Status: Kapanmış · 2018
Summary
Neuropathic pain is an increasing health problem in society. Researchers studying neuropathic pain have consensus that inflammatory and immune processes are key factors in the pathophysiology of neuropathic pain. Recent studies focus on glial cell activation and neuroglial interactions. Peripheral nerve injury converts resting spinal cord glia into reactive cells that are required for the development and maintenance of neuropathic pain. Clarification of glial activation steps is very significant in understanding pathophysiology of neuropathic pain and targeting neuropathic pain treatment. Therefore, in the present study, we investigated the time-dependent changes in certain glial activation steps in a rat model of sciatic nerve ligation. Neuropathic pain was induced by loose ligation of right sciatic nerve of female and male rats with 4.0 silk under anesthesia. Pain thresholds were measured by dynamic plantar estesiometer, plantar test and analgesimeter on postoperative 2nd, 7th, 14th, 21st and 29th days to evaluate tactile allodynia, thermal hyperalgesia and mechanical hyperalgesia respectively. At the end of the experimental period, rats were sacrificed under anesthesia, the spinal cord lumbar section was removed and total protein was extracted. Spinal cord STAT3 (signal transducer and transcription activator 3), phosphorylated STAT3 and GFAP (glial fibrillary acid protein) protein expressions were evaluated by Western blotting after SDS-PAGE electrophoresis. Rats with neuropathic pain did not lose weight, even they gained weight similar to control rats at 14th, 21st, and 29th days. Significant decreases in pain threshold were detected in all tests on the 2nd, 7th, 14th and 21st days after sciatic nerve ligation. The decrease in pain threshold was accompanied by an increase in GFAP protein expression in the spinal cord significantly on days 2 and 14. There were no statistically significant differences over time in STAT3 or phosphorylated STAT3 protein expression in the spinal cord. In conclusion, our model of sciatic nerve loose ligation using surgical silk in adult rats resulted in tactile allodynia continuing for 14 days as well as thermal and mechanical hyperalgesia continuing for 21 days. Recovery was observed on day 29. Lack of expected weight loss and autotomy of the classical sciatic nerve ligation model, early recovery from decreased pain thresholds and increased spinal GFAP protein expression and lack of changes in spinal STAT3 and phosphorylated STAT3 expression all together suggest the requirement of additional mechanistic studies.