Central effects of systemic lidocaine mediated by glycine spinal receptors: an iontophoretic study in the rat spinal cord.
The objective of this investigation was to demonstrate the possible interactions of systemic lidocaine (lido) with inhibitory receptors in the spinal cord. In the lumbar dorsal horn of anesthetized and curarized rats, 60 physiologically identified, wide dynamic range (WDR) neurons, were recorded extracellularly. Glutamate, glycine and its selective antagonist, strychnine, were iontophoretically applied onto the neurons either singularly or concurrently. The effects of systemic lido on the drug-induced frequency changes and the interaction with the glycine receptors, using strychnine as a probe, were studied. It was consistently found that: (i) lido (3-4 mg/kg) inhibited the excitatory responses to iontophoretic glutamate, (ii) this inhibition was significantly antagonized by concurrent iontophoretic strychnine, (iii) iontophoretic glycine induced comparable glutamate inhibition that was reversed by strychnine. In contrast, no effect on glutamate-induced excitations was observed when lido was applied by micropressure or a different local anesthetic was systemically administered. The results suggest that central inhibitory effects of lido could be mediated by spinal strychnine-sensitive glycine receptors, activated by lido itself or possibly by its glycine residue-bearing metabolites.
Biella
G
G
Istituto di Fisiopatologia e Terapia del Dolore, Facoltà di Medicina, Università di Milano, Italy.
Sotgiu
M L
ML
D000818:Animals; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid; D007275:Injections, Intravenous; D007478:Iontophoresis; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D005971:Glutamates; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D008012:Lidocaine; D013331:Strychnine