Fine structural correlates of VIP-like immunoreactivity in the upper spinal dorsal horn after peripheral axotomy: possibilities of a neuro-glial translocation of a neuropeptide.

After transection of the peripheral nerve, VIP-like immunoreactivity (VIPLI) increases markedly in the ipsilateral upper dorsal horn of the spinal cord. Immunoreactivity has been studied by means of light- and electron microscopic immunocytochemistry. Under normal conditions, there is little VIPLI present in the superficial dorsal horn, confined to small dot-like elements corresponding to axonal and glial profiles. At the electron microscopic level, immunostaining was found mainly in preterminal and, partly, also in en passant terminal swellings or varicosities. The reaction was confined to the axoplasm and, to a lesser extent, to large dense core vesicles. VIPLI is also present in several astroglial processes. 13, 19, and 25 d after transection of the sciatic nerve, increased immunoreactivity was present in the medial 2/3 of the superficial dorsal horn. Electron microscopically, VIPLI was seen mainly in preterminal axons and in many astroglial processes surrounding axon terminals while VIPLI in the en passant axon terminals themselves decreases. 2 months after peripheral axotomy, the amount of axonally localized VIPLI decreases considerably and most of the immunocytochemically detectable VIPLI is found in expansions and processes of astroglial cells. Perikarya of glial cells rarely exhibit VIPLI. VIPLI also increased after crushing the related peripheral nerve; however, as soon as the nerve fibers regenerate, VIPLI decreases again to normal levels. It appears that blockade of the retrograde axoplasmic transport induces a switch in the neuropeptide synthesizing machinery of dorsal root ganglion cells which results in the expression of VIP instead of substance P, somatostatin and CGRP. It is proposed that VIP is released from axon terminals affected by transganglionic degenerative atrophy. Subsequently, astroglial cells equipped with receptors for VIP, might bind and internalize the released VIP.