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J. Pharm. Pharmacol. · Aug 2011
Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced peripheral neuropathic pain.
- Kuang-I Cheng, Hung-Chen Wang, Chung-Sheng Lai, Hung-Pei Tsai, Aij-Lie Kwan, Shung-Tai Ho, Jhi-Joung Wang, and Lin-Li Chang.
- Graduate Institute of Medicine, Department of Anesthesiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
- J. Pharm. Pharmacol. 2011 Aug 1;63(8):1063-9.
ObjectivesQuinidine, a class I anti-arrhythmic agent, is a sodium channel blocker that is more potent than lidocaine and mexiletine. This study tested pre-emptive intrathecal quinidine to attenuate neuropathic pain induced by lumbar spinal nerve ligation (SNL).MethodsNinety-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 pretreated with intrathecal quinidine 35 mM (50 µl); group Q₇₀, SNL pretreated with 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) and spinal microglia activation in spinal dorsal horn.Key FindingsSpinal nerve ligation induced abnormal mechanical allodynia and thermal hyperalgesia, up-regulated Nav₁.₃ in DRG, and activated microglia in spinal cord. Group Q₇₀ showed attenuated thermal hyperalgesia (P<0.001) and mechanical allodynia (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 and significantly attenuated microglia activation on POD₇ (P=0.032) in spinal cord.ConclusionsPretreatment with intrathecal quinidine 70 mM before SNL attenuates nerve ligation-induced neuropathic pain. The duration of the effect is 5 days.© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.
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