original abstract†Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
BACKGROUND: The attempted healing of tendon after acute injury (overloading, partial tear or complete rupture) proceeds via the normal wound healing cascade involving hemostasis, inflammation, matrix synthesis and matrix remodeling. Depending on the degree of trauma and the nature of the post-injury milieu, a variable degree of healing and recovery of function occurs. Post-injury analgesia is often achieved with NSAIDs such as Ibuprofen, however there is increasing evidence that NSAID usage may interfere with the healing process. This study aimed to investigate the cellular mechanism by which IBU therapy might lead to a worsening of tendon pathology.
METHODS: We have examined the effect of oral Ibuprofen, on Achilles tendon healing in a TGFb1-induced murine tendinopathy model. Dosing was started 3 days after initial injury (acute cellular response phase) and continued for 22 days or started at 9 days after injury (transition to matrix regeneration phase) and given for 16 days. Cellular changes in tendon and surrounding peritenon were assessed using Hematoxylin/Eosin, chondroid accumulation with Safranin O and anti-aggrecan immunohistochemistry, and neo-vessel formation with GSI Lectin histochemistry. Markers of inflammation included histochemical localization of hyaluronan, immunohistochemistry of heavy chain 1 and TNFα-stimulated glycoprotein-6 (TSG6). Cell responses were further examined by RT-qPCR of 84 NFκB target genes and 84 wound healing genes. Biomechanical properties of tendons were evaluated by tensile testing.
RESULTS: At a clinically-relevant dosage, Ibuprofen prevented the process of remodeling/removal of the inflammatory matrix components, hyaluronan, HC1 and TSG6. Furthermore, the aberrant matrix remodeling was accompanied by activation at day 28 of genes (Col1a2, Col5a3, Plat, Ccl12, Itga4, Stat3, Vegfa, Mif, Col4a1, Rhoa, Relb, F8, Cxcl9, Lta, Ltb, Ccl12, Cdkn1a, Ccl22, Sele, Cd80), which were not activated at any time without the drug, and so appear most likely to be involved in the pathology. Of these, Vegfa, Col4a1, F8, Cxcl9 and Sele, have been shown to play a role in vascular remodeling, consistent with the appearance at 25 days of vasculogenic cell groups in the peritenon and fat pad stroma surrounding the Achilles of the drug-dosed mice. Tensile stiffness (p = 0.004) and elastic modulus (p = 0.012) were both decreased (relative to age-matched uninjured and non-dosed mice) in mice dosed with Ibuprofen from day 3 to day 25, whether injured or not.
CONCLUSION: We conclude that the use of Ibuprofen for pain relief during inflammatory phases of tendinopathy, might interfere with the normal processes of extracellular matrix remodeling and cellular control of expression of inflammatory and wound healing genes. It is proposed that the known COX2-mediated anti-inflammatory effect of ibuprofen has detrimental effects on the turnover of a pro-inflammatory HA matrix produced in response to soft-tissue injury, thus preventing the switch to cellular responses associated with functional matrix remodeling and eventual healing.
- “Effects of anti-inflammatory (NSAID) treatment on human tendinopathic tissue,” Katja Maria Heinemeier, Tommy F Øhlenschlæger, Ulla Ramer Mikkelsen, Freja Sønder, Peter Schjerling, Rene B Svensson, and Michael Kjaer, J Appl Physiol (1985), 2017.
These six articles on PainScience.com cite Bittermann 2018 as a source:
- Icing for Injuries, Tendinitis, and Inflammation — Become a cryotherapy master
- Save Yourself from Patellofemoral Pain Syndrome! — Patellofemoral pain syndrome (aka runner’s knee) explained and discussed in great detail, including every imaginable self-treatment option and all the available scientific evidence
- Save Yourself from Tennis Elbow! — Not just for tennis players, straight-talking advice on healing from this common tendinitis (lateral epicondylitis)
- Save Yourself from Muscle Strain! — Muscle strain (pulled muscle) and muscle pain explained and discussed in great detail, plus every imaginable treatment option
- Repetitive Strain Injuries Tutorial — Five surprising and important facts about repetitive strain injuries like carpal tunnel syndrome, tendinitis, or iliotibial band syndrome
- Achilles Tendinitis Treatment Science — Evidence-based guidelines for recovering as fast as possible
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial. Munteanu 2015 Br J Sports Med.
- A Bayesian model-averaged meta-analysis of the power pose effect with informed and default priors: the case of felt power. Gronau 2017 Comprehensive Results in Social Psychology.
- The neck and headaches. Bogduk 2014 Neurol Clin.
- Agreement of self-reported items and clinically assessed nerve root involvement (or sciatica) in a primary care setting. Konstantinou 2012 Eur Spine J.
- Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis. Morelli 2017 Am J Sports Med.