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Overexpression of copper/zinc‐superoxide dismutase in transgenic mice markedly impairs regeneration and increases development of neuropathic pain after sciatic nerve injury
Author(s) -
Kotulska Katarzyna,
LePecheur Marie,
Marcol Wiesław,
LewinKowalik Joanna,
LaryszBrysz Magdalena,
Paly Evelyn,
Matuszek Iwona,
London Jacqueline
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21000
Subject(s) - autotomy , sciatic nerve , sod1 , neuropathic pain , regeneration (biology) , nerve injury , superoxide dismutase , denervation , peripheral nerve injury , sciatic nerve injury , nociception , atrophy , neuroma , inflammation , medicine , axotomy , oxidative stress , endocrinology , anesthesia , anatomy , microbiology and biotechnology , biology , surgery , receptor
Abstract Despite the general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function, sometimes with the burden of neuropathic pain. The mechanisms of both regeneration and nociception have not been clarified, but it is known that inflammatory reactions are involved. Cu/Zn‐superoxide dismutase (SOD1) is an important scavenger protein that acts against oxidative stress. It has been shown to play an important role in apoptosis and inflammation. The aim of this study was to examine the role of SOD1 overexpression in peripheral nerve regeneration and neuropathic pain‐related behavior in mice. Sciatic nerves of SOD1‐overexpressing and FVB/N wild type‐mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4 weeks of followup. We found markedly worse sciatic function index outcome as well as more significant atrophy of denervated muscles in SOD1‐overexpressing animals compared with wild type. Autotomy was markedly worse in SOD1 transgenic mice than in wild‐type animals. Histological evaluation revealed that the intensity of regeneration features, including numbers of GAP‐43‐positive growth cones, Schwann cells, and macrophages in the distal stump of the transected nerve, was also decreased in transgenic mice. Neuroma formation at the injury site was significantly more prominent in this group. Taken together, our findings suggest that SOD1 overexpression is deleterious for nerve regeneration processes and aggravates neuropathic pain‐like state in mice. This can be at least partially ascribed to disturbed inflammatory reactions at the injury site. © 2006 Wiley‐Liss, Inc.