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Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury.
Connect Tissue Res 2019; :1-16CT

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.

Authors+Show Affiliations

Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.Department of Anatomy and Cell Biology, Lewis Katz School of Medicine, Temple University , Philadelphia , PA , USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31443618

Citation

Barbe, M F., et al. "Blocking Substance P Signaling Reduces Musculotendinous and Dermal Fibrosis and Sensorimotor Declines in a Rat Model of Overuse Injury." Connective Tissue Research, 2019, pp. 1-16.
Barbe MF, Hilliard BA, Fisher PW, et al. Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury. Connect Tissue Res. 2019.
Barbe, M. F., Hilliard, B. A., Fisher, P. W., White, A. R., Delany, S. P., Iannarone, V. J., ... Popoff, S. N. (2019). Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury. Connective Tissue Research, pp. 1-16. doi:10.1080/03008207.2019.1653289.
Barbe MF, et al. Blocking Substance P Signaling Reduces Musculotendinous and Dermal Fibrosis and Sensorimotor Declines in a Rat Model of Overuse Injury. Connect Tissue Res. 2019 Aug 23;1-16. PubMed PMID: 31443618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blocking substance P signaling reduces musculotendinous and dermal fibrosis and sensorimotor declines in a rat model of overuse injury. AU - Barbe,M F, AU - Hilliard,B A, AU - Fisher,P W, AU - White,A R, AU - Delany,S P, AU - Iannarone,V J, AU - Harris,M Y, AU - Amin,M, AU - Cruz,G E, AU - Popoff,S N, Y1 - 2019/08/23/ PY - 2019/8/25/entrez KW - Work-related musculoskeletal disorders (WMSDs) KW - isometric pull KW - repetitive motion disorders KW - repetitive strain injuries (RSI) KW - tendinopathy SP - 1 EP - 16 JF - Connective tissue research JO - Connect. Tissue Res. N2 - 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. SN - 1607-8438 UR - https://www.unboundmedicine.com/medline/citation/31443618/Blocking_substance_P_signaling_reduces_musculotendinous_and_dermal_fibrosis_and_sensorimotor_declines_in_a_rat_model_of_overuse_injury L2 - http://www.tandfonline.com/doi/full/10.1080/03008207.2019.1653289 DB - PRIME DP - Unbound Medicine ER -