Intrathecal lidocaine pretreatment attenuates immediate neuropathic pain by modulating Nav1.3 expression and decreasing spinal microglial activation

<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 L₆transverse process; (2) ligated (Group L), which underwent left L₅spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L₅SNL 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_1.3and Nav_1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD₃) and 7 (POD₇).</p> <p>Results</p> <p>Group L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav_1.3and down-regulation of Nav_1.8, and showed increased microglial activation. Compared with ligation only, pretreatment with intrathecal lidocaine before nerve injury (Group P), as measured on POD₃, palliated both mechanical allodynia (<it>p </it>< 0.01) and thermal hyperalgesia (<it>p </it>< 0.001), attenuated Nav_1.3up-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 POD₇(<it>p </it>= 0.002).</p> <p>Conclusions</p> <p>Intrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav_1.3up-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