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Non-peptidergic nociceptive neurons are essential for mechanical inflammatory hypersensitivity in mice
Pinto, Larissa G; Souza, Guilherme R; Sant'Anna, Morena Brazil Martins; Kusuda, Ricardo; Lopes, Alexandre H; Cunha, Fernando Q; Ferreira, Sérgio H; Cunha, Thiago M.
Afiliação
  • Souza, Guilherme R; Instituto Butantan. Laboratório Especial de Dor e Sinalização (LEDS).
Mol Neurobiol ; 56(8): p. 5715–5728, 2019.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib16117
Biblioteca responsável: BR78.1
Localização: BR78.1
ABSTRACT
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 (P2X3) 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 PGE2 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.
Texto completo: Disponível Coleções: Bases de dados nacionais / Brasil Base de dados: Sec. Est. Saúde SP / SESSP-IBPROD Idioma: Inglês Revista: Mol Neurobiol Ano de publicação: 2019 Tipo de documento: Artigo
Texto completo: Disponível Coleções: Bases de dados nacionais / Brasil Base de dados: Sec. Est. Saúde SP / SESSP-IBPROD Idioma: Inglês Revista: Mol Neurobiol Ano de publicação: 2019 Tipo de documento: Artigo
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