| Summary: | 博士 === 高雄醫學大學 === 醫學研究所 === 99 === Background: Intrathecal Na channel blocker pretreatment has been demonstrated to alleviate postoperative pain. However, its effect to neuropathic pain is not determined. Therefore, the study is to investigate intrathecal Na channel blocker prior to spinal nerve ligation in rats and evaluates the effect via neurobehavioral examination in hindpaws, sodium channel expressions in injured dorsal root ganglion and glial cells expressions in spinal dorsal horn.
Methods: The part one study: Sixty 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). The part two study: Ninety-six adult male Sprague-Dawley rats were grouped equally (n=24 per group) as follows: Group S (sham): removal of transverse process only; group L: SNL; group Q35: SNL with pretreatment of intrathecal quinidine 35 mM (50 µl); group Q70: SNL with pretreatment of intrathecal quinidine 70 mM (50 µl). Neuropathic pain was measured by thermal hyperalgesia and mechanical allodynia. Other measurements included dys-regulation of sodium channel Nav1.3 in dorsal root ganglion (DRG), spinal microglia activations in spinal dorsal horn.
Results: Part one: Group 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). Part two: Results showed spinal nerve ligation induced abnormal mechanical allodynia and thermal hyperalgesia; up-regulated Nav1.3 in DRG; activated microglia in spinal cord. Group Q70 attenuated mechanical allodynia (p<0.001) and thermal hyperalgesia (p<0.05) on postoperative day 5 (POD5) but not on POD7; reversed up-regulated expression of Nav1.3 on POD3 and POD7 in DRG; significantly attenuated microglia activation on POD7 (p=0.026) in spinal cord.
Conclusion: Intrathecal 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. In addition, pretreatment with intrathecal quinidine 70 mM before SNL attenuates nerve ligation-induced neuropathic pain. The duration of the effect is 5 days.
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