Nerve reinnervation and itch behavior in a rat burn wound model

Abstract

In this study, we investigated whether postburn itch in rats, after a full thickness burn, is correlated to the nervous reinnervation of the burn wound area. For this purpose, we determined scratching duration (expressed as second/hour) at 24 hours, 2, 4, 8, and 12 weeks postburn and combined this with immunohistochemistry for protein gene product 9.5 (PGP9.5) to identify all nerve fibers, calcitonin gene related peptide (CGRP) to identify peptidergic fibers, tyrosine hydroxylase (TH) for sympathetic fibers, and growth-associated protein 43 (GAP-43) for regrowing fibers. We found a modest, but highly significant, increase in scratching duration of all burn wound rats from 3 to 12 weeks postburn (maximally 63 ± 9.5 second/hour compared to sham 3.1 ± 1.4 second/hour at 9 weeks). At 24 hours postburn, all nerve fibers had disappeared from the burn area. Around 4 weeks postburn PGP 9.5- and CGRP-immunoreactive nerve fibers returned to control levels. TH- and GAP-43-IR nerve fibers, which we found to be almost completely colocalized, did not regrow. No correlation was found between scratching duration and nervous reinnervation of the skin. The present results suggest that in rat, like in human, burn wound healing will induce increased scratching, which is not correlated to the appearance of nervous reinnervation.

“Out of Touch”—Recovering Sensibility after Burn Injury: A Review of the Literature

“…In their rat model, PGP 9.5-and CGRP-immunoreactive nerve fibers reappeared four weeks after the burn injury, while H-and GAP-43-IR nerve fibers remained absent. Peptidergic and non/peptidergic nerve fibers, except sympathetic noradrenergic nerve fibers, could be verified in the developed scar tissue 2 weeks after a full-thickness injury and returned to normal 8-12 weeks after burn trauma in the center of the lesion [21].…”

“…Splitting perception into single sensory qualities, the animal studies revealed that 8 weeks after full-thickness burn injury, nociceptive function is renewed, mainly in distant sites and reduced in the wound center and at the edges [20]. Saffari et al [21] reported that 24 h after thermal insult, nerve fibers were completely absent in the wound. In their rat model, PGP 9.5-and CGRP-immunoreactive nerve fibers reappeared four weeks after the burn injury, while H-and GAP-43-IR nerve fibers remained absent.…”