Sprouting of CGRP primary afferents in lumbosacral spinal cord precedes emergence of bladder activity after spinal injury.
Spinal cord injury (SCI) severely disrupts bladder function. What mediates bladder dysfunction after SCI is currently unknown. We investigated the role that primary afferent sprouting in lumbosacral cord may play in emergence of bladder activity after complete spinal cord transection. Rats had a bladder cannula chronically implanted. They were then subjected to complete surgical spinal cord transection at T9/T10. Cystometrographic analysis (0.1 ml/min) after injury revealed that bladder activity emerged in the form of nonvoiding contractions in all rats at approximately 5 days post transection. At 10-14 days after transection nonvoiding contractions remained and voiding contractions emerged that had increased maximal pressures (12-41 vs. 24-57 cmH(2)O) but were less efficient (6-15% vs. 79-100%) when compared to control implanted rats. We looked for sprouting 3 days and 8 days post transection, timepoints preceding the emergence of nonvoiding and voiding contractions respectively. Increases in CGRP density and distribution were seen in L6 and S1 spinal cord within lamina groupings of II-IV, V and VI, as well as lamina X at 8 days post transection. This increase remained in most lamina at 21 days post transection. Colocalization with the growth cone marker Gap-43 3 days and 5 days post transection at the level of the lumbosacral preganglionic nucleus verified that CGRP positive afferents were sprouting in L6/S1 spinal cord prior to emergence in bladder activity. These data provide support for the hypothesis that primary afferent sprouting contributes to emergence of bladder activity after spinal cord transection.
Zinck
N D T
ND
Department of Pharmacology, Dalhousie University, Sir Charles Tupper Medical Building, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5. nzinck@dal.ca
Rafuse
V F
VF
Downie
J W
JW
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D008161:Lumbosacral Region; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation / Q000503:physiopathology*
D019922:GAP-43 Protein; D015740:Calcitonin Gene-Related Peptide