Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced peripheral neuropathic pain

Abstract

Objectives: Quinidine, 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). Methods: 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 Q 35, SNL pretreated with intrathecal quinidine 35 μm (50 μl); group Q 70, 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 Nav 1.3 in dorsal root ganglion (DRG) and spinal microglia activation in spinal dorsal horn. Key findings: Spinal nerve ligation induced abnormal mechanical allodynia and thermal hyperalgesia, up-regulated Nav 1.3 in DRG, and activated microglia in spinal cord. Group Q 70 showed attenuated thermal hyperalgesia (P < 0.001) and mechanical allodynia (P < 0.05) on postoperative day 5 (POD 5) but not on POD 7, reversed up-regulated expression of Nav 1.3 on POD 3 and POD 7 in DRG and significantly attenuated microglia activation on POD 7 (P = 0.032) in spinal cord. Conclusions: Pretreatment 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.