Peptides, Vol. 7, Suppl. I, pp. 205-219, 1986. ¢ AnkhoInternational Inc. Printed in the U.S.A. 01960781/86 $3.00 + .00 A VIP/PHI-Containing Pathway Links Urinary Bladder and Sacral Spinal Cord S. J. GIBSON, J. M. POLAK, t P. ANAND,* M. A. BLANK,* Y. YIANGOU,* H. C. SU, G. TERENGHI, T. KATAGIRI, J. F. B. MORRISON,t B. M. LUMB,t C. INYAMA AND S. R. BLOOM* Departments of Histoehemistry and *Medicine, Royal Postgraduate Medieal School Hammersmith Hospital, London WI2 0HS, U.K. and +Department of Physiology, Leeds University, Leeds, U.K. GIBSON, S. J., J. M. POLAK, P. ANAND, M. A. BLANK, Y. YIANGOU, H. C. SU, G. TERENGHI, T. KATAGIRI, J. F. B. MORRISON, B. M. LUMB, C. INYAMA AND S. R. BLOOM. A VlP/PHl-containingpathway links urinary bladder and sacral spinal cord. PEPTIDES 7: Suppl. I, 205-219, 1986.--Nerve fibres containing VIP and the co-produced PHI are found in the dorsal horn and autonomic centres of the sacral spinal cord and in pelvic organs. We have investigated the origin of these nerve fibres and a possible peptide-containing pathway linking pelvic viscera with the spinal cord of the cat and rat using neurochemical and neurosurgical procedures, retrograde tracing and immunocytochemistry. Cell bodies were located in the dorsal root ganglia (after colchicine injection), pelvic ganglia and bladder wall. Capsaicin treatment induced a loss of VIP/PHI from the dorsal horn. Retrograde tracing from the bladder revealed True Blue labelled cells in the dorsal root ganglia (L,~, S.), parasympathetic nuclei and pelvic ganglia. Labelled cells were sequentially immunostained for VIP/PHI which were numerous in pelvic ganglia and scattered and weak in dorsal root ganglia. Pelvic nerve section induced a decrease of VIP/PHI immunoreactivity from the spinal cord and no change or a minimal increase in immunoreactive nerve fibers of the bladder. Thus pelvic visceral afferents with cell bodies in the dorsal root ganglia are a significant source of VIP/PHl-containing fibres in the sacral dorsal horn. Capsaicin Dorsal root ganglia lmmunocytochemistry Lumbar spinal cord Pelvic nerve section Pelvic ganglion Radioimmunoassay Retrograde tracing Sacral spinal cord Lateral dorsal horn Lissauer's tract Peptide histidine isoleucine Vasoactive intestinal polypeptide A large number of peptides have been identified in the mammalian spinal cord [20, 23, 24, 26, 31,34, 37, 57, 59, 63, 73], and most of these are found in higher concentrations in the lumbosacral segments of the spinal cord than in cervical and thoracic levels [2, 25, 26, 55, 68, 71,72]. A novel peptide has recently been discovered and termed PHI (peptide histidine isoleucine) [77,78]. PHI has been shown to be encoded with VIP in the same precursor molecule [10,38]. VIP/PHI are co-distributed in many tissues including the spinal cord [3, 7, 59]. When compared to other neuropeptides, the distribution of VIP/PHI is exceptional with relatively much higher levels and a distinctive distribution in lumbosacral segments [2, 3, 5, 11, 15, 25, 34, 43]. Since sacral pathways play the major role in the neural control of urogenital function [46,49], the investigation of peptide-containing pathways which link the pelvic viscera with sensory areas and visceromotor centres of the sacral spinal cord is of considerable importance. Anatomical evidence of the distribution of afferent fibres from the pelvic viscera, namely the large intestine and blad- der, projecting to specific regions of the sacral spinal cord, was provided by the tracing studies of de Groat and col- leagues [18,60]. The distribution of VIP/PHI-immunore- active fibres in the dorsal horn [2, 3, 5, 11, 25, 34] closely parallels the central projections of afferent terminals of the pelvic nerve [60]. Dorsal rhizotomy or sacral ganglionec- tomy dramatically reduces the levels of VIP [25, 34, 43] and PHI (own unpublished data) in the sacral spinal cord indicat- ing the presence of these peptides in afferent fibres which reach the cord via the sacral dorsal roots. We have therefore sought to investigate further the VIP/PHI-containing pathway which links the urinary bladder to the spinal cord, using pharmacological or surgical manipu- lations and retrograde tracing alone or in combination with immunocytochemistry. METHOD Experimental Manipulations All animals undergoing surgery were anaesthetised with 'Requests for reprints should be addressed to J. M. Polak, Department of Histochemistry, RPMS, Hammersmith Hospital, London W12 OHS, U.K. 205