Long-term follow-up of peptidergic and nonpeptidergic reinnervation of the epidermis following sciatic nerve reconstruction in rats.
OBJECTIVE
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.
Departments of 1 Neuroscience and.|Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.
Shoista
S
Kambiz
Departments of 1 Neuroscience and.|Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.
Liron S
LS
Duraku
Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.
Martijn
M
Baas
Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.
Tim H J
TH
Nijhuis
Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.
Saniye G
SG
Cosgun
Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.
Steven E R
SE
Hovius
Departments of 1 Neuroscience and.
Tom J H
TJ
Ruigrok
Plastic, Reconstructive and Hand Surgery, Erasmus University Medical Center, Rotterdam, Zuid-Holland, The Netherlands; and.|Department of Plastic Surgery, Radboud UMC, Nijmegen, Gelderland, The Netherlands.
Erik T
ET
Walbeehm
D000818:Animals; D004195:Disease Models, Animal; D004817:Epidermis / Q000294:innervation*; D005260:Female; D005500:Follow-Up Studies; D008137:Longitudinal Studies; D009412:Nerve Fibers / Q000145:classification* / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009437:Neuralgia / Q000601:surgery; D059348:Peripheral Nerve Injuries / Q000601:surgery; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000601:surgery*; D013997:Time Factors; D016896:Treatment Outcome
CGRP = calcitonin gene–related peptide; CMAP = compound muscle action potential; GDNF = glial cell line–derived neurotrophic factor; GMI = gastrocnemius muscle index; IENF = intra-epidermal nerve fiber; IR = immunoreactive; LC = Langerhans cells; NF200 = neurofilament 200; NGF = nerve growth factor; SubP = substance P; TRP = transient receptor potential; end-to-end reconstruction; intra-epidermal nerve fibers; neuropathic pain; nonpeptidergic nerve fibers; peptidergic nerve fibers