title: A novel spinal action of mexiletine in spinal somatosensory transmission of nerve injured rats.
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.
authors.affiliation: Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Victoria
authors.initials: V
authors.lastname: Chapman
authors.forename: Jane
authors.initials: J
authors.lastname: Ng
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D008026:Ligation; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013127:Spinal Nerves / Q000166:cytology / Q000293:injuries* / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D008801:Mexiletine