| Summary: | <p>Abstract</p> <p>Background</p> <p>Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain.</p> <p>Methods</p> <p>Sixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L<sub>6 </sub>transverse process; (2) ligated (Group L), which underwent left L<sub>5 </sub>spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L<sub>5 </sub>SNL and was pretreated with intrathecal 2% lidocaine (50 μl). Neuropathic pain was assessed based on behavioral responses to thermal and mechanical stimuli. Expression of sodium channels (Nav<sub>1.3 </sub>and Nav<sub>1.8</sub>) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD<sub>3</sub>) and 7 (POD<sub>7</sub>).</p> <p>Results</p> <p>Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav<sub>1.3 </sub>and down-regulation of Nav<sub>1.8</sub>, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD<sub>3</sub>, palliated both mechanical allodynia (<it>p </it>< 0.01) and thermal hyperalgesia (<it>p </it>< 0.001), attenuated Nav<sub>1.3 </sub>up-regulation (<it>p </it>= 0.003), and mitigated spinal microglial activation (<it>p </it>= 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (<it>p </it>= 0.034). p38 activation was also suppressed on POD<sub>7 </sub>(<it>p </it>= 0.002).</p> <p>Conclusions</p> <p>Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav<sub>1.3 </sub>up-regulation and suppressing activation of spinal microglia. Although its effects are limited to 3 days, intrathecal lidocaine pretreatment can alleviate acute SNL-induced neuropathic pain.</p>
|
|---|