Non-Peptidergic Nociceptive Neurons Are Essential for Mechanical Inflammatory Hypersensitivity in Mice

Autor(es)

Pinto, Larissa G. ^{[1, 2]} ; Souza, Guilherme R. ^[1] ; Kusuda, Ricardo ^[1] ; Lopes, Alexandre H. ^[1] ; Sant'Anna, Morena B. ^{[3, 1]} ; Cunha, Fernando Q. ^[1] ; Ferreira, Sergio H. ^[1] ; Cunha, Thiago M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Bandeirantes Ave 3900, BR-14049900 Sao Paulo - Brazil

^[2] Kings Coll London, Wolfson Ctr Age Related Dis, Guys Campus, London - England

^[3] Butantan Inst, Lab Pain & Signaling, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 56, n. 8, p. 5715-5728, AUG 2019.
• Citações Web of Science: 1

Resumo

Small nerve fibers that bind the isolectin B4 (IB4(+) C-fibers) are a subpopulation of primary afferent neurons that are involved in nociceptive sensory transduction and do not express the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Several studies have attempted to elucidate the functional role of IB4(+)-nociceptors in different models of pain. However, a functional characterization of the non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice is still lacking. To this end, in the present study, the neurotoxin IB4-Saporin (IB4-Sap) was employed to ablate non-peptidergic C-fibers. Firstly, we showed that intrathecal (i.t.) administration of IB4-Sap in mice depleted non-peptidergic C-fibers, since it decreased the expression of purinoceptor 3 (P2X(3)) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the dorsal root ganglia (DRGs) as well as IB4 labelling in the spinal cord. Non-peptidergic C-fibers depletion did not alter the mechanical nociceptive threshold, but it inhibited the mechanical inflammatory hypersensitivity induced by glial cell-derived neurotrophic factor (GDNF), but not nerve growth factor (NGF). Depletion of non-peptidergic C-fibers abrogated mechanical inflammatory hypersensitivity induced by carrageenan. Finally, it was found that the inflammatory mediators PGE(2) and epinephrine produced a mechanical inflammatory hypersensitivity that was also blocked by depletion of non-peptidergic C-fibers. These data suggest that IB4-positive nociceptive nerve fibers are not involved in normal mechanical nociception but are sensitised by inflammatory stimuli and play a crucial role in mediating mechanical inflammatory hypersensitivity. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 10/04043-8 - Investigação do papel das fibras c não-peptidérgicas na nocicepção aguda e crônica
• Beneficiário: Larissa Garcia Pinto
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Temático