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Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
Spinal afferents innervating the
gastrointestinal tract are the major pathways for visceral nociception.
Many centrally acting analgesic drugs attenuate responses of visceral
primary afferent fibers by acting at the peripheral site.
-Amino
butyric acid (GABA), a major inhibitory neurotransmitter, acts via
metobotropic GABAB and ionotropic
GABAA/GABAC receptors. The aim of this study was to test the peripheral effect of selective GABAB
receptor agonist baclofen on responses of the pelvic nerve afferent
fibers innervating the colon of the rat. Distension-sensitive pelvic nerve afferent fibers were recorded from the S1 sacral
dorsal root in anesthetized rats. The effect of baclofen (1-300
µmol/kg) was tested on responses of these fibers to colorectal
distension (CRD; 60 mmHg, 30 s). A total of 21 pelvic nerve
afferent fibers was recorded. Mechanosensitive properties of four
fibers were also recorded before and after bilateral transections of
T12-S3 ventral roots (VR). Effect of baclofen
was tested on 15 fibers (7 in intact rats, 4 in rats with transected
VR, and 4 in rats pretreated with CGP 54626). In nine fibers (5/7 in
intact and 4/4 in VR transected rats), baclofen produced dose-dependent
inhibition of response to CRD. Pretreatment with selective
GABAB receptor antagonist CGP 54626 (1 µmol/kg) reversed
the inhibitory effect of baclofen. Results suggest a peripheral role of
GABAB receptors in the inhibition of mechanotransduction
property of distension-sensitive pelvic nerve afferent fibers.
baclofen; visceral pain; spinal cord; sacral nerve; ventral roots
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