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The interaction between intrathecal neostigmine and GABA receptor agonists in rats with nerve ligation Injury.
Hwang, J H; Hwang, K S; Kim, J U; Choi, I C; Park, P H; Han, S M.
Afiliação
  • Hwang JH; Department of Anesthesiology, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, Korea. jhhwang@amc.seoul.kr
Anesth Analg ; 93(5): 1297-303, 2001 Nov.
Article em En | MEDLINE | ID: mdl-11682418
UNLABELLED: Nerve ligation injury may produce a pain syndrome that includes tactile allodynia. Reversal effects on tactile allodynia have been demonstrated after the intrathecal administration of gamma-aminobutyric acid (GABA) receptor agonists or cholinesterase inhibitors in rats. We examined the drug interactions between neostigmine and muscimol or baclofen in a rat model of nerve ligation injury. Rats were prepared with tight ligation of the left L5-6 spinal nerves and chronic intrathecal catheter implantation. Tactile allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hindpaw. Thresholds for paw withdrawal were assessed. Neostigmine (0.3-10 microg), muscimol (0.1-10 microg), and baclofen (0.1-3.0 microg) were administered to obtain the dose-response curve and the 50% effective dose (ED(50)). Fractions of ED(50) values were administered intrathecally to establish the ED(50)s of drug combinations (neostigmine-muscimol and neostigmine-baclofen). The drug interactions were performed. Intrathecal neostigmine, muscimol, baclofen, and their combinations produced a dose-dependent increase in withdrawal threshold of the lesioned hindpaw. Both analyses revealed a synergistic interaction for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination was additive. These results suggest that the activation of both muscarinic and GABA(A) receptors is required for synergistic interaction. IMPLICATIONS: This study indicates that drug interaction is synergistic for the neostigmine-muscimol combination, whereas the effect of the neostigmine-baclofen combination is additive. In a rat model of nerve ligation injury, neostigmine, muscimol, baclofen, and their combinations provide an antagonism on touch-evoked allodynia at the spinal level.
Assuntos
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Base de dados: MEDLINE Assunto principal: Baclofeno / Inibidores da Colinesterase / Agonistas GABAérgicos / Muscimol / Neostigmina / Neuralgia Idioma: En Ano de publicação: 2001 Tipo de documento: Article
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Base de dados: MEDLINE Assunto principal: Baclofeno / Inibidores da Colinesterase / Agonistas GABAérgicos / Muscimol / Neostigmina / Neuralgia Idioma: En Ano de publicação: 2001 Tipo de documento: Article