Cutaneous effects of nerve injury : An experimental study in the rat

Abstract: One of the most difficult tasks of the hand surgeon is to reach a satisfactory restoration of the nerve functions of the injuried hand. In spite of the use of meticulous microsurgery, the results of nerve repair are disappointing, particularly with respect to mixed nerve trunks. In order to understand better the factors influencing axon regeneration and to improve further the outcome of surgical nerve repair, experimental studies are imperative. Studies in the rat show that the number of axons crossing a sharp sciatic nerve lesion may be high at nerve trunk level, whereas the sensibility of the foot skin is very deficient. This mismatch led us to study, with immunohistochemistry, the restoration of nerve endings in rat foot skin after various nerve injuries. In addition, some effects of nerve injury on the non-nervous epidermal components are elucidated through histology, autoradiography and immunohistochemistry. The results show that the occurrence of epidermal protein gene product 9.5 (PGP 9.5) immunoreactive axon profiles in the skin of the foot is statistically normal3 months after a crush lesion, but deficient 3 months after sciatic neurotomy and suture. The epidermal axon profiles return late after neurotomy and suture. The occurrence of {putative sensory) calcitonin gene-related peptide- and/or substance P-immunoreactive profiles, and {putative sympathetic) tyrosine hydroxylase-immunoreactive axon profiles in rat foot skin is partly abnormal after sciatic nerve crush and very abnormal after sciatic neurotomy and suture, when the contralateral side is also affected. In rats subjected to sciatic neurotomy and suture or neurectomy, the plantar epidermis becomes abnormally thin, but this is not seen after nerve crush. The epidermal thinning concurs with a decreased occurrence of mitotic cells. Both sutured and neurectornized rats, but not crushed cases, showed a markedly abnormal gait. However, rats subjected to selective division of sciatic foot branches exhibited a normal postural and locomotor behavior. In these rats, the occurrence of mitotic epidermal cells was similar on the operated and contralateral sides. This indicates that the effect of sciatic nerve division on the epidennal thickness of rat plantar skin is indirect, probably being caused by an ab~onnal load situation. The presence of PGP 9.5-immunoreactive epidermal dendritic cells in rat plantar skin is statistically normal3 months after sciatic crush injury, but significantly increased 1 week-3 months after neurotomy and suture. Finally, we show that the epidermal PGP 9.5- imrnunoreactive dendritic cells present in rat plantar skin represent la-immunoreactive Langerhans cells and that the plantar skin of albino rats is devoid ofepidermal NKJ-immunoreactive melanocytes.