Dexamethasone reduced substance P expression in human tendon cells through a glucocorticoid receptor-dependent pathway, revealing for the first time why corticosteroid injections relieve tendon pain.
Substance P Substantially DecreasedDexamethasone reduced both SP gene expression and protein levels in tendon cells through the glucocorticoid receptor, even blocking SP induction by inflammation and mechanical stress
What the researchers found
Dexamethasone exposure leads to a time-dependent decrease in substance P (SP) mRNA and protein levels in human tendon fibroblasts via glucocorticoid receptor signaling, without affecting the SP receptor NK1R. It also inhibits SP induction by IL-1β and mechanical loading.
Why it matters
Understanding that dexamethasone reduces substance P in tendon cells reveals a potential mechanism for its pain-relieving effects in tendinopathy, guiding future therapies targeting SP signaling to treat tendon pain.
How the study worked
Human tendon fibroblasts from hamstrings and Achilles tendons were cultured and treated with varying concentrations of dexamethasone and other modulators. Gene expression of SP (TAC1), NK1R, and inflammatory cytokines was measured by quantitative PCR, and SP protein levels were assessed by enzyme immunoassay and western blot.
What this study cannot tell us
The study was conducted in vitro using isolated human tendon cells, which may not fully replicate the complex environment of tendons in living organisms. The study type and evidence strength were not specified, limiting assessment of clinical applicability.
How to read the evidence
This is an in vitro mechanistic study using primary human tendon cells. While it uses human tissue (from both hamstrings and Achilles tendons) and multiple validation methods (qPCR, EIA, western blot), the findings are from isolated cell cultures and haven't been confirmed in intact human tendons or clinical settings.
When this study was published
Published in 2015 in Rheumatology, this study established a mechanistic basis for corticosteroid pain relief in tendinopathy. Subsequent research has built on these findings to explore substance P-targeted therapies for tendon pain.
The bigger picture
Substance P is one of the most important neuropeptides in pain signaling, and its role in tendon disease has been increasingly recognized. This study bridges the gap between clinical practice (corticosteroid injections for tendinopathy) and basic science (neuropeptide pain signaling). Understanding that steroids work partly by suppressing substance P opens the door to developing more targeted therapies — drugs that specifically block substance P signaling without the side effects of corticosteroids like tissue weakening.
Questions still open
- Could NK1R antagonists (drugs that block the substance P receptor) provide similar pain relief to corticosteroids without the tissue-weakening side effects?
- Does substance P suppression explain why corticosteroid injections provide only temporary relief — does SP production rebound when the drug wears off?
- How do other neuropeptides involved in tendon pain (like CGRP) respond to corticosteroid treatment?
Common questions
What is substance P and why does it cause tendon pain?
Could there be a better alternative to steroid injections for tendon pain?
Read the original research
Dexamethasone decreases substance P expression in human tendon cells: an in vitro study.
Rheumatology (Oxford, England), 54(2), 318-23
Citation
Mousavizadeh, Rouhollah; Backman, Ludvig; McCormack, Robert G; Scott, Alex. (2015). Dexamethasone decreases substance P expression in human tendon cells: an in vitro study.. Rheumatology (Oxford, England), 54(2), 318-23. https://doi.org/10.1093/rheumatology/keu315