Publications

Latest publication 08/23/2019

Blocking substance P signaling reduces musculotendinous and dermal fibrosis and

Purpose/Aim: Substance P-NK-1R signaling has been implicated in fibrotic tendinopathies and myositis. Blocking this signaling with a neurokinin 1...

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    [title] => Blocking substance P signaling reduces musculotendinous and dermal fibrosis and 
    [paragraph] => Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury
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Authors
Barbe MF, Hilliard BA, Fisher PW, White AR et al

 Lab
Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.
Journal
Connective Tissue Research
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 and Methods: 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.
BIOSEB Instruments Used
Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT)
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An operator independent test to study pain thresholds in rodents (mouse and rat) by assessing temperature preference (thermal comfort zone) - a new tool for your analgesia/nociception research opening new fields of investigation, and an ideal solution for nociceptive and analgesic drugs screening. Now comes with a brand new software, allowing tracking activity and faster temperature transitions!

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