Brain Research, 372 (1986) 37-44 37 Elsevier BRE 11633 Vasoactive Intestinal Polypeptide (VIP) Increases in the Spinal Cord after Peripheral Axotomy of the Sciatic Nerve Originate from Primary Afferent Neurons S.A.S. SHEHAB and M.E. ATKINSON Department of Anatomy and Cell Biology, University of Sheffield, Sheffield $10 2 TN ( U.K.) (Accepted August 27th, 1985) Key words: axotomy - - immunohistochemistry - - vasoactive intestinal polypeptide - - spinal cord - - neuropeptide Following sciatic nerve axotomy, vasoactive intestinal polypeptide (VIP) immunoreactivity increases dramatically in the central terminal areas of the nerve whereas other primary afferent neuropeptides are depleted. The contribution of the peripheral nerve to VIP increases in the spinal cord was investigated by performing sciatic nerve section alone, dorsal rhizotomy of the lumbar roots, axo- tomy and rhizotomy in combination or section of other peripheral nerves terminating in the same segments as the sciatic nerve. VIP, and for comparison, substance P (SP), cholecystokinin (CCK), somatostatin (SOM), were localized in the lumbar spinal cord and cor- responding sensory ganglia using unlabeled antibody immunohistochemistry. After sciatic nerve section, SP, CCK and SOM were de- pleted in the lumbar dorsal horn whereas VIP increased. After rhizotomy alone all neuropeptide staining including VIP was depleted; axotomy followed by rhizotomy produced the same result. Axotomy of other peripheral nerves terminating in the lumbar cord in- creased the area of neuropeptide depletion but correspondingly increased the area of VIP staining. A large proportion of small and medium diameter dorsal root ganglion cells were stained for VIP after nerve section or axotomy but not after rhizotomy alone. A radi- cal change in neuropeptide metabolism of dorsal root ganglion cells occurs after peripheral axotomy, in the form of a marked increase in VIP synthesis. An intact dorsal root is necessary for increases in VIP in the spinal cord indicating the primary afferent origin of the response. INTRODUCTION It has recently been demonstrated by two indepen- dent groups that vasoactive intestinal polypeptide (VIP) increases in the terminal areas of the sciatic nerve following peripheral axotomy13,15,16. VIP in- creases only in the specific terminal regions of the sci- atic nerve from which other primary afferent neuro- peptides, substance P (SP), cholecystokinin (CCK) and somatostatin (SOM) are depleted and staining for the enzymatic marker of the primary afferent neurons, fluoride resistant acid phosphatase (FRAP), is abolished15.16. Furthermore, VIP in- crease appears to be a general response to peripheral axotomy, as it occurs in the trigeminal nucleus cauda- lis after mandibular trigeminal nerve section 2 as well as the lumbosacral spinal cord which is particularly rich in VIP 5 corresponding to the termination of pel- vic parasympathetic splanchnic nervesl,6, 7. Although VIP-positive cell bodies are relatively sparse in the spinal cord, they have been demonstrated in the su- perficial laminae of the dorsal horn following intra- spinal colchinine 5 and have been suggested as the ori- gin of the increased VIP seen after peripheral axoto- my 13. However, preliminary evidence from the pres- ent authors has shown that VIP staining of cell bodies in both dorsal root ganglia and trigeminal ganglia, which is normally absentS, increases quite dramat- ically following either sciatic or mandibular nerve pe- ripheral axotomy2.16 suggesting a peripheral origin. This could be from the cell bodies of axotomized nerves or from the perikarya of unaffected neurons in the same ganglia sprouting into the vacated area of the spinal cord. The reason for this bizarre response of VIP to peripheral nerve section compared with de- pletion of other peptides is not easy to explain and will remain so until the source of increased VIP is known. Furthermore, the significance of the VIP re- sponse to axotomy must also remain speculative. We therefore investigated the possible source of Correspondence: M.E. Atkinson, Department of Anatomy and Cell Biology, University of Sheffield, Sheffield S10 2TN, U.K. 0006-8993/86/$03.50 (~ 1986 Elsevier Science Publishers B.V. (Biomedical Division)