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

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 mu g) 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 (F-5,F-55 = 2.5, P less than or equal to 0.05). The spinal neurones of the sham operated rats exhibited negligible spontaneous activity. The electrically evoked A beta-fibre neuronal responses of SNL and sham operated rats were not significantly influenced by spinal mexiletine. In contrast, the A delta-fibre and C-fibre evoked neuronal responses of the SNL rats, but not sham operated rats, were significantly reduced by spinal mexiletine (F-5,F-52 = 4.9, P less than or equal to 0.001 and F-5,F-48 = 12, P less than or equal to 0.0001, respectively). In addition, the mechanical punctate von Prey 9 and 50 g evoked neuronal responses of the SNL rats, but not sham operated rats, were significantly reduced by spinal mexiletine (F-5,F-57 = 4.3, P less than or equal to 0.002 and F-5,F-52 = 6.1, P less than or equal to 0.001). This pharmacological study suggests that following nerve injury there is a novel mexiletine sensitive spinal substrate which contributes to A delta-fibre and C-fibre, but not A beta-fibre, somatosensory transmission. This central action may underlie some of the clinical efficacy of mexiletine in the treatment of neuropathic pain states. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V.