title: Nonsteroidal anti-inflammatory drug reduces neutrophil and macrophage accumulation but does not improve tendon regeneration.
abstract: Whether nonsteroidal anti-inflammatory drugs have a beneficial effect on tendon regeneration is still a matter of debate. Given that inflammatory cells are thought to induce nonspecific damage following an injury, we tested the hypothesis that a 3-day treatment with diclofenac would protect tendons from inflammatory cell injury and would promote healing. Neutrophil and ED1(+) macrophage concentrations were determined in the paratenon and the core of the rat Achilles tendon following collagenase-induced injury. Hydroxyproline content, edema, and mechanical properties were also evaluated at 1, 3, 7, 14, and 28 days post-trauma. Collagenase injections induced a 70% decrease in the ultimate rupture point at Day 3. Diclofenac treatments (1 mg/kg bid) selectively decreased the accumulation of neutrophils and ED1(+) macrophages by 59% and 35%, respectively, in the paratenon, where blood vessels are numerous, but did not reduce the accumulation of neutrophils and ED1(+) macrophages in the core of the tendon. Edema was significantly reduced on Day 3 but persisted during the remodeling phase in the diclofenac-treated group only. The inhibition of leukocyte accumulation by diclofenac did not translate into a reduction of tissue damage or a promotion of tissue healing, because the mechanical properties of injured Achilles tendons were identical in placebo and diclofenac-treated groups. These results indicate that diclofenac reduced both edema and the accumulation of inflammatory cells within the paratenon but provided no biochemical or functional benefits for the Achilles tendon.
authors.affiliation: Department of Rehabilitation, Faculty of Medicine, Université Laval, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Marsolais
authors.forename: Claude H
authors.initials: CH
authors.lastname: Côté
authors.forename: Jérôme
authors.initials: J
authors.lastname: Frenette
mesh_terms: D000125:Achilles Tendon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D004487:Edema / Q000473:pathology; D005260:Female; D006614:Hindlimb; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013314:Stress, Mechanical; D013708:Tendon Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D006909:Hydroxyproline