Immunoreactive Vasoactive Intestinal Polypeptide Is Concentrated in the Sacral Spinal Cord: A Possible Marker for Pelvic Visceral Afferent Fibers

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Abstract
Previous descriptions of immunoreactive vasoactive intestinal polypeptide (VIP) in small-diameter dorsal root ganglion cells in the superficial dorsal horn implicated this 28 amino acid peptide in nociceptive transmission. In this study, we examined the distribution of immunoreactive VIP in the spinal cord and caudal medulla of cats and rats. The PAP method was used on paraffin and frozen sections of 4% paraformaldehyde-fixed tissue, using antibodies to VIP that were raised in rabbits. The distribution of immunoreactive VIP, while similar to that of substance P (SP), a putative primary afferent peptide neurotransmitter, is more restricted. VIP staining is found in sacral dorsal roots and densely in the Lissauer tract. Dorsal horn staining is concentrated in lamina I. In contrast to SP, lamina II is almost devoid of staining. Labeled VIP axons course along the lateral curvature of the dorsal horn and arborize across lamina V and around the central canal. A collateral branch of these fibers distributes to the sacral autonomic nucleus. A few fibers could be traced from the root entry zone to the contralateral central gray. VIP axons also terminate between ependymal cells of the central canal. Unlike SP, immunoreactive VIP was restricted, almost exclusively, to the sacral cord. The few fibers in the lumbar enlargement and in the coccygeal cord apparently derive from ascending and descending sacral primary afferents. In fact, the VIP pattern is almost identical to that reported for afferents from the pelvic viscera, including a discontinuous rostrocaudal distribution. Since the staining pattern is also very similar to that of A-delta high-threshold mechanoreceptors, the possibility is discussed that whereas VIP is not a general “somatic” primary afferent transmitter, it may transmit nociceptive input from the pelvic viscera.