Acute and chronic sectioning of fifth lumbar spinal nerve has equivalent effects on the primary afferents of sciatic nerve in rat spinal cord.

The mechanism of neuropathic pain may be associated with sprouting of uninjured primary afferents of peripheral nerves into regions of the spinal cord denervated through peripheral injury. However, this remains controversial. Therefore, the purpose of the present investigation was, first, to determine in detail the central distributions of the unmyelinated primary afferents of each of the L4, L5, and L6 components of sciatic nerve, then to assess the distribution of afferent sciatic terminals following acute and chronic injury to (L5) nerve. First, we injected isolectin B4 (IB4), into the sciatic nerves in three groups of rats, each of which had two of the three L4, L5, or L6 components ligated and cut, and the one remaining, uninjured. Although the terminal labelling found in the L5 segment of the spinal cord originated from the L5 component, some terminal labelling remained in cases when either the L4 or L6 component was intact. Second, tracers transported in predominantly unmyelinated (IB4 and WGA-HRP) or myelinated (cholera toxin subunit B) nerves were injected into the sciatic nerve following acute or chronic (21-day) injury restricted to the L5 component. In each case, the central distribution of nerve terminals in the spinal dorsal horn was equivalent following either acute or chronic injury to the L5 component. Consequently, these data provide no support for the suggestion that neuropathic pain in spinal ligation model results from uninjured L4 and L6 components sprouting to occupy sites vacated by the injured L5 component of the sciatic nerve.

Do central terminals of intact myelinated primary afferents sprout into the superficial dorsal horn of rat spinal cord after injury to a neighboring peripheral nerve?

In order to investigate whether normal myelinated primary afferent axons sprout into the territories of adjacent injured peripheral nerve fibers in the superficial dorsal horn of the spinal cord, adult rats underwent either sectioning of the saphenous or femoral nerves on one side, or else unilateral denervation of the skin of the posterior thigh. Two weeks later cholera toxin B subunit (CTb), which is normally transported selectively by myelinated somatic primary afferents, was injected into the ipsilateral (intact) sciatic nerve. The relationship between CTb, vasoactive intestinal peptide (VIP), and binding of Bandeiraea simplicifolia isolectin B4 (IB4) was then examined in the ipsilateral dorsal horn of the second to fifth lumbar spinal segments (L2-L5). Sectioning of the femoral or saphenous nerves resulted in a reduction of IB4 binding in laminae I-II in the medial third of the dorsal horn of L2, L3, and the upper part of L4. VIP-immunoreactivity was upregulated in exactly the same regions in which IB4-binding was reduced. These correspond to the areas that were previously innervated by unmyelinated afferents in the sectioned nerves. CTb-labeling was detected in regions known to receive input from myelinated sciatic afferents: lamina I and a band extending from the inner part of lamina II (IIi) to lamina V in the L3-5 segments, and the deepest part of the dorsal horn in L2. Importantly, no CTb-labeling was detected in the outer part of lamina II (IIo) in the denervated areas. Sectioning of branches of the posterior cutaneous nerve of the thigh resulted in a reduction of IB4-binding and upregulation of VIP-immunoreactivity in the lateral part of the superficial dorsal horn of caudal L4 and L5. Again, CTb-immunoreactivity showed the normal sciatic pattern in L4-L5, with no labeling detected in lamina IIo in the denervated region. These results do not support the suggestion that the central terminals of intact myelinated afferents sprout into regions of lamina II occupied by adjacent nerves that have been axotomized peripherally.