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  • Title: Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced peripheral neuropathic pain.
    Author: Cheng KI, Wang HC, Lai CS, Tsai HP, Kwan AL, Ho ST, Wang JJ, Chang LL.
    Journal: J Pharm Pharmacol; 2011 Aug; 63(8):1063-9. PubMed ID: 21718290.
    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 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 FINDINGS: Spinal 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. CONCLUSIONS: 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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