Changes in nociceptive sensory innervation in the epidermis of the rat lower lip skin in a model of neuropathic pain

The epidermis is innervated by fine nerve endings that are important in the perception of nociceptive stimuli. However, their role in neuropathic pain is controversial. In this paper, changes in the innervation patterns of epidermal sensory afferent fibres in the rat lower lip have been studied following bilateral chronic constriction injury (CCI) of the mental nerve-a purely sensory branch of the trigeminal nerve. Sections of the lower lip were processed for immunocytochemistry using antibodies against Protein Gene Product (PGP) 9.5 and Calcitonin Gene-Related Peptide (CGRP) to identify the non-peptidergic and the peptidergic populations of nociceptive small diameter primary sensory afferent fibres. Peptidergic fibres co-localised both markers and the non-peptidergic fibres only stained for PGP 9.5 and not for CGRP. We quantified the total fibre length per 6000 μm2 in the epidermis at several time points following CCI. Our data indicate that both fibre populations were significantly decreased at 2 weeks post-CCI, followed by fibre re-growth at levels above those seen in sham-operated animals at 4 weeks; however, this increase was only statistically significant for the non-peptidergic population. At 8 weeks post-CCI, the fibre lengths of both populations did not differ significantly from shams. This transient hyper-innervation of the epidermis by one subpopulation of nociceptive fibres coincided with the occurrence of spontaneous pain or dysesthetic sensations which we detected in a previous study in the same animal model. Therefore, we speculate that this transient hyper-innervation of the epidermis following injury could play a role in nociception in these animals.