GABAB Receptor Agonist Baclofen
Has Non-Specific Antinociceptive Effect in the Model of Peripheral
Neuropathy in the Rat
M. FRANĚK, Š. VACULÍN, R. ROKYTA
Department of Normal, Pathological and Clinical Physiology, Third Faculty
of Medicine, Charles University, Prague, Czech Republic
Received July 25, 2003
Accepted November 7, 2003
Summary
Baclofen, which is a specific agonist of the metabotropic GABAB
receptor, is used in clinical practice for the treatment of spasticity of
skeletal muscles. It also exerts an analgesic effect, but this effect is
still not clear and especially controversial in neuropathic pain. In this
work, we studied the antinociceptive effects of baclofen in a model of
chronic peripheral neuropathic pain – loose ligation of the sciatic nerve
(chronic constriction injury, CCI). As controls we used sham-operated
animals. The changes of thermal pain threshold were measured using the
plantar test 15-25 days after the operation. The obtained results suggest
that baclofen increases pain threshold in both groups. The antinociceptive
effect of baclofen was dose-dependent and the maximum response without
motor deficits was observed at a dose of 15 mg/kg s.c. In the rats with
CCI, significant differences between affected (ipsilateral) and
contralateral hind paw were present. This difference was dose-dependent,
the highest value (6.2±1.37 s) was found at the
dose of 20 mg/kg. Based on our results and previous findings it could be
summarized that baclofen has antinociceptive action, which is attenuated
in the model of chronic neuropathic pain probably due to the degeneration
of GABA interneurons after chronic constriction injury.
Key words
Baclofen • GABAB receptor • Chronic constriction injury • Antinociception
• Rat
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