A NOVEL SPINAL ACTION OF MEXILETINE IN SPINAL SOMATOSENSORY TRANSMISSION OF NERVE INJURED RATS

Mexiletine is widely used for the treatment of neuropathic pain althou gh its site(s) of action remain unclear. Here we have studied the effe ct of spinal administration of mexiletine (10-1000 mu g) on the sponta neous and peripherally evoked responses of spinal neurones of nerve in jured (selective ligation of spinal nerves L5-L6; SNL) rats. Sham cont rols for the surgical intervention were performed. A high proportion o f the spinal neurones of SNL rats exhibited de novo spontaneous activi ty (mean frequency of firing 4 +/- 1 Hz), this activity was highly sen sitive 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 negligib le spontaneous activity. The electrically evoked A beta-fibre neuronal responses of SNL and sham operated rats were not significantly influe nced 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 le ss 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 opera ted 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 ne rve injury there is a novel mexiletine sensitive spinal substrate whic h contributes to A delta-fibre and C-fibre, but not A beta-fibre, soma tosensory transmission. This central action may underlie some of the c linical efficacy of mexiletine in the treatment of neuropathic pain st ates. (C) 1998 International Association for the Study of Pain. Publis hed by Elsevier Science B.V.