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Articles in PresS, published online ahead of print September 25, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00124.2002
Submitted on April 1, 2002
Accepted on August 27, 2002
1 Department of Gastroeterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI, USA
* To whom correspondence should be addressed. E-mail: sengupta{at}mcw.edu.
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. The
-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 seconds). A total of 21 pelvic nerve afferent fibers were recorded. Mechanosensitive properties of 4 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.
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