title: Consequences of the ablation of nonpeptidergic afferents in an animal model of trigeminal neuropathic pain.
abstract: 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, P2X(3)-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.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3G 1Y6 Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada H3A 0G1 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada H3A 0C7.
authors.forename: Anna M W
authors.initials: AMW
authors.lastname: Taylor
authors.forename: Maria
authors.initials: M
authors.lastname: Osikowicz
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ribeiro-da-Silva
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects / Q000601:surgery; D000818:Animals; D004195:Disease Models, Animal; D037102:Lectins / Q000494:pharmacology*; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054789:Ribosome Inactivating Proteins, Type 1 / Q000494:pharmacology*; D000076985:Saporins; D061221:Trigeminal Nerve Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D014277:Trigeminal Neuralgia / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
chemical_list: C496198:IB4-saporin conjugate; D037102:Lectins; D010455:Peptides; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins