Comparing effects of rest with or without a NK1RA on fibrosis and sensorimotor declines induced by a voluntary moderate demand task

Authors
MF Barbe, AR White, BA Hilliard, DM Salvadeo et al

Lab
Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA

Journal
Journal of Musculoskeletal and Neuronal Interactions

Abstract
Fibrosis is one contributing factor in motor dysfunction and discomfort in patients with overuse musculoskeletal disorders. We pharmacologically targeted the primary receptor for Substance P, neurokinin-1, using a specific antagonist (NK1RA) in a rat model of overuse with the goal of improving tissue fibrosis and discomfort. Methods: Female rats performed a low repetition, high force (LRHF) grasping task for 12 weeks, or performed the task for 12weeks before being placed on a four week rest break, with or without simultaneous NK1RA treatment. Results were compared to control rats (untreated, or treated 4 weeks with NK1RA or vehicle). Results: Rest improved LRHF-induced declines in grip strength, although rest plus NK1RA treatment (Rest /NK1RA) rescued it. Both treatments improved LRHF-induced increases in muscle TGFbeta1 and collagen type 1 levels, forepaw mechanical hypersensitivity (Rest/NK1RA more effectively), macrophage influx into median nerves, and enhanced collagen deposition in forepaw dermis. Only Rest/NK1RA reduced muscle hypercellularity. However, LRHF+4wk Rest /NK1RA rats showed hyposensitivity to noxious hot temperatures. Conclusions: While the NK1RA induced hot temperature hyposensitivity should be taken into consideration if this or related drug were used long-term, the NK1RA more effectively reduced muscle hypercellularity and improved grip strength and forepaw mechanical hypersensitivity.

BIOSEB Instruments Used:
Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT)