Ablation of nonpeptidergic nociceptive afferents exacerbated the nociceptive responses following a neuropathic lesion, suggesting a complex role in the development of neuropathic pain.
Damage to peripheral nerves causes significant remodeling of peripheral innervation and can lead to neuropathic pain. Most nociceptive primary afferents are unmyelinated (C fibers) and subdivided into peptidergic and nonpeptidergic fibers. Previous studies have found nerve injury in the trigeminal system to induce changes in small-diameter primary afferent innervation and cause significant autonomic sprouting into the upper dermis of the lower-lip skin of the rat. In this study, we used the ribosomal toxin, saporin, conjugated to the lectin IB4 to specifically ablate the nonpeptidergic nociceptive C fibers, to see if loss of these fibers was enough to induce autonomic fiber sprouting. IB4-saporin treatment led to specific and permanent ablation of the IB4-positive, P2X3-immunoreactive fibers and led to sprouting of parasympathetic fibers into the upper dermis, but not of sympathetic fibers. These changes were associated with significant increase in glial-derived nerve growth factor levels in the lower-lip skin. While IB4-saporin treatment had no effect on evoked mechanical thresholds when von Frey hairs were applied to the lower-lip skin, ablation of nonpeptidergic fibers in a chronic constriction injury model caused significant sympathetic and parasympathetic fiber sprouting, and led to an exacerbated pain response. This was an unexpected finding, as it has been suggested that nonpeptidergic fibers play a major role in mechanical pain, and suggests that these fibers play a complex role in the development of neuropathic pain.
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aDepartment of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1Y6
bAlan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada H3A 0G1
cDepartment of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 0C7
*Corresponding author. Address: Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Quebec, Canada H3G 1Y6. Tel.: +1 514 398 3619; fax: +1 514 221 3207.
Article history: Received 23 December 2011; Received in revised form 15 February 2012; Accepted 21 March 2012.