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Published on: June 7, 2024
Comparing effects of rest with or without a NK1RA on fibrosis and sensorimotor declines induced by a voluntary
Mary F Barbe1, Amanda R White1, Brendan A Hilliard1
1Anatomy and Cell Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, USA.
Objectives:
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 12 weeks 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 TGFβ1 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.
