| Full text | |
| Author(s): |
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
|
| Affiliation: | [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: | 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 (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: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| 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 Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Projects - Thematic Grants |