ABSTRACT
An exem ption to this concept is posed by the pathology w hich Clostridium difficile toxin A induces in the ra t ileum . In this m odel the level o f CGRP in afferent neu ro n s in c rease s , a n d fro m th e effec t o f CGRPs-37 it appears as if CGRP contributes to the d ia rrhea , in flam m ation and tissue destruction caused by the toxin.50,75
Since CGRP is a transm itter substance o f spinal afferent neurons innervating the gut, it is natu ra l to th in k o f an im plication o f this peptide in visceral nociception (Fig. 12.4). W ith th e use o f C G R P8-37 it has indeed been possible to ob tain experim en tal evidence tha t CGRP participates in vis ceral pain reactions. For instance, in traperitoneal adm inistra tion o f acetic acid causes a p rostaglandin-m ediated release o f CGRP fro m a ffe ren t nerv e fibers an d triggers a b d o m in a l m uscle c o n tra c tio n s , a p a in reaction th a t is m im icked by intravenous CGRP.39,106 The nociceptive response to ace tic acid, prostaglandin Eļ and E2 as well as CGRP is inh ib ited by capsa icin -induced ablation o f extrinsic afferents and p retrea t m en t w ith CGRP8_37.39,106 In travenous or in trathecal adm in istra tion o f CGRP8_37 is likewise able to prevent acetic acid-evoked colonic inflam m ation from facilitating the pain response to rectal d isten tion .107
