Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury.
Connect Tissue Res
; 61(6): 604-619, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-31443618
ABSTRACT
Purpose/Aim:
Substance P-NK-1R signaling has been implicated in fibrotic tendinopathies and myositis. Blocking this signaling with a neurokinin 1 receptor antagonist (NK1RA) has been proposed as a therapeutic target for their treatment.Materials andMethods:
Using a rodent model of overuse injury, we pharmacologically blocked Substance P using a specific NK1RA with the hopes of reducing forelimb tendon, muscle and dermal fibrogenic changes and associated pain-related behaviors. Young adult rats learned to pull at high force levels across a 5-week period, before performing a high repetition high force (HRHF) task for 3 weeks (2 h/day, 3 days/week). HRHF rats were untreated or treated in task weeks 2 and 3 with the NK1RA, i.p. Control rats received vehicle or NK1RA treatments.Results:
Grip strength declined in untreated HRHF rats, and mechanical sensitivity and temperature aversion increased compared to controls; these changes were improved by NK1RA treatment (L-732,138). NK1RA treatment also reduced HRHF-induced thickening in flexor digitorum epitendons, and HRHF-induced increases of TGFbeta1, CCN2/CTGF, and collagen type 1 in flexor digitorum muscles. In the forepaw upper dermis, task-induced increases in collagen deposition were reduced by NK1RA treatment.Conclusions:
Our findings indicate that Substance P plays a role in the development of fibrogenic responses and subsequent discomfort in forelimb tissues involved in performing a high demand repetitive forceful task.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tendões
/
Transtornos Traumáticos Cumulativos
/
Transdução de Sinais
/
Substância P
/
Músculo Esquelético
/
Derme
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Connect Tissue Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos