A novel spinal action of mexiletine in spinal somatosensory transmission of nerve injured rats

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Abstract
Mexiletine is widely used for the treatment of neuropathic pain although its site(s) of action remain unclear. Here we have studied the effect of spinal administration of mexiletine (10-1000 microg) on the spontaneous and peripherally evoked responses of spinal neurones of nerve injured (selective ligation of spinal nerves L5-L6; SNL) rats. Sham controls for the surgical intervention were performed. A high proportion of the spinal neurones of SNL rats exhibited de novo spontaneous activity (mean frequency of firing 4+/-1 Hz), this activity was highly sensitive to spinal mexiletine (F5,55 = 2.5, P < or = 0.05). The spinal neurones of the sham operated rats exhibited negligible spontaneous activity. The electrically evoked Abeta-fibre neuronal responses of SNL and sham operated rats were not significantly influenced by spinal mexiletine. In contrast, the Adelta-fibre and C-fibre evoked neuronal responses of the SNL rats, but not sham operated rats, were significantly reduced by spinal mexiletine (F5.52 = 4.9, P < or = 0.001 and F5,48 = 12, P < or = 0.0001, respectively). In addition, the mechanical punctate von Frey 9 and 50 g evoked neuronal responses of the SNL rats, but not sham operated rats, were significantly reduced by spinal mexiletine (F5,57 = 4.3, P < or = 0.002 and F5,52 = 6.1, P < or = 0.001). This pharmacological study suggests that following nerve injury there is a novel mexiletine sensitive spinal substrate which contributes to Adelta-fibre and C-fibre, but not Abeta-fibre, somatosensory transmission. This central action may underlie some of the clinical efficacy of mexiletine in the treatment of neuropathic pain states.

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