Systemic tocainide relieves mechanical hypersensitivity and normalizes the responses of hyperexcitable dorsal horn wide-dynamic-range neurons after transient spinal cord ischemia in rats.
In the present study we examined the effect of systemic tocainide on sensory hypersensitivity in rats after spinal cord ischemia induced by a photochemical technique. After induction of spinal cord ischemia the rats exhibited a sensory disturbance which was mainly expressed as vocalization to innocuous cutaneous mechanical stimuli (allodynia) in the flank area during the following several days. Tocainide at 75 mg/kg i.p., but not 50 mg/kg i.p., significantly increased the vocalization threshold to mechanical pressure for 2 h. The effect of intraarterial (i.a.) tocainide on the responses of dorsal horn wide-dynamic-range (WDR) neurons to suprathreshold electrical stimulation of their receptive fields was also examined in normal rats and after transient spinal cord ischemia, at a time when the animals exhibited typical behavioral allodynia in the dermatomes innervated by the ischemic spinal segments. In normal rats, tocainide (50 mg/kg i.a.) strongly suppressed the responses of WDR neurons to C fiber input with lesser effect on A fiber input. In allodynic rats, tocainide suppressed the augmented A and C fiber mediated responses of WDR neurons to the extent that their responses were similar to those seen in normal rats without tocainide. There was no difference in the overall depression of A and C fiber mediated input by tocainide between normal and allodynic rats. The present results demonstrated the analgesic effect of systemic tocainide in relieving allodynia in rats and indicated that systemic local anesthetics, at doses that do not block nerve conduction, can be effective in suppressing dorsal horn WDR neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hao
J X
JX
Department of Clinical Physiology, Huddinge University Hospital, Sweden.
Yu
Y X
YX
Seiger
A
A
Wiesenfeld-Hallin
Z
Z
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D006967:Hypersensitivity / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply* / Q000187:drug effects; D016677:Tocainide / Q000494:pharmacology*
D016677:Tocainide