Abstract
BackgroundIntrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain.MethodsSixty six adult male Sprague-Dawley rats were divided into three treatment groups: (1) sham (Group S), which underwent removal of the L6 transverse process; (2) ligated (Group L), which underwent left L5 spinal nerve ligation (SNL); and (3) pretreated (Group P), which underwent L5 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 (Nav1.3 and Nav1.8) in injured dorsal root ganglia and microglial proliferation/activation in the spinal cord were measured on post-operative days 3 (POD3) and 7 (POD7).ResultsGroup L presented abnormal behavioral responses indicative of mechanical allodynia and thermal hyperalgesia, exhibited up-regulation of Nav1.3 and down-regulation of Nav1.8, 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 (p < 0.01) and thermal hyperalgesia (p < 0.001), attenuated Nav1.3 up-regulation (p = 0.003), and mitigated spinal microglial activation (p = 0.026) by inhibiting phosphorylation (activation) of p38 MAP kinase (p = 0.034). p38 activation was also suppressed on POD7 (p = 0.002).ConclusionsIntrathecal lidocaine prior to SNL blunts the response to noxious stimuli by attenuating Nav1.3 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.
Highlights
Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain
We found that intrathecal lidocaine pretreatment alleviated pain-related thermal hyperalgesia and mechanical allodynia, attenuated up-regulation of Nav1.3 in the injured DRG, and significantly reduced spinal microglial activation on post-operative day 3 (POD3)
Multiple activated microglia were observed in the ipsilateral dorsal horn of the spinal cord after spinal nerve ligation (SNL), as shown in Figure 3B (POD3; p = 0.004) and 3D (POD7; p = 0.008)
Summary
Intrathecal lidocaine reverses tactile allodynia after nerve injury, but whether neuropathic pain is attenuated by intrathecal lidocaine pretreatment is uncertain. Peripheral nerve injury caused by disease or surgery, such as limb and colon amputation, nerve dissection, mastectomy, and thoracotomy, often results in neuropathic pain [1]. Intrathecal lidocaine after peripheral nerve injury reverses well-developed tactile allodynia either through interaction with eicosanoid systems in the spinal dorsal horn or by attenuating phosphorylation of p38 mitogen-activated protein (MAP) kinase in activated microglia of the spinal cord [12,13,14]. The effectiveness of intrathecal lidocaine pretreatment in reducing neuropathic pain was evaluated by behavioral testing, by measuring dysregulation of sodium channel a-subunit (Nav1.3 and Nav1.8) expression in dorsal root ganglia (DRGs), and by measuring spinal microglial activation in the spinal cord. Intrathecal lidocaine administration before peripheral nerve injury can attenuate neuropathic pain for 3 days
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