Long-term follow-up of peptidergic and nonpeptidergic reinnervation of the epidermis following sciatic nerve reconstruction in rats

OBJECT: Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional deficits. The current gold standard for transected nerves is an end-to-end reconstruction, which results in the intermittent appearance of neuropathic pain. METHODS: To improve our understanding of the relation between this type of reconstruction and neuropathic pain, the authors transected and immediately end-to-end reconstructed the sciatic nerve in rats. The effect of this procedure on neuropathic pain, as measured by thermal and mechanical hypersensitivity at 4 different time points (5, 10, 20, and 30 weeks), was related to the density of peptidergic and nonpeptidergic fiber innervation in the glabrous skin of rats' hind paws. RESULTS: Thermal hypersensitivity occurring 20 weeks after reconstruction was accompanied by a significant increase in peptidergic epidermal fibers. However, the lesion-induced reduction in the density of nonpeptidergic epidermal fibers remained decreased at all experimental time points. Moreover, temporal collateral sprouting by undamaged saphenous nerve was visualized using the recently revised Evans blue extravasation technique. Strikingly, as the sciatic nerve repopulated rats' hind paw, the saphenous nerve withdrew to its original territory. CONCLUSIONS: The authors conclude that the transient thermal hypersensitivity is related to increased density of epidermal peptidergic fibers, which mainly originate from regenerating fibers. Furthermore, a changed composition in the peptidergic and nonpeptidergic epidermal fibers is demonstrated following end-to-end reconstruction of the sciatic nerve