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

Abstract

AbstractObjectivesQuinidine, 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.