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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 8
[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
Total Affiliations: 3
Document type: Journal article
Source: Molecular Neurobiology; v. 56, n. 8, p. 5715-5728, AUG 2019.
Web of Science Citations: 0

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)

FAPESP's process: 10/04043-8 - Investigation of the role of non-peptidergic c fibers in the acute and chronic nociception
Grantee:Larissa Garcia Pinto
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support type: Research Projects - Thematic Grants