Comparison of Photobiomodulation and Anti-Inflammatory Drugs on Tissue Repair on Collagenase-Induced Achilles Tendon Inflammation in Rats.

BACKGROUND: Tendinopathy is characterized by pain, edema, and structural changes in tendon tissue. OBJECTIVE: In this animal study we decided to compare the short- and medium-term effects of low-level laser therapy (LLLT), dexamethasone, and diclofenac on inflammation and tendon tissue repair in collagenase-induced tendinitis. MATERIALS AND METHODS: Two hundred five female Wistar rats were randomly divided into five groups. Animals in the control group were given a saline injection and the experimental groups received a collagenase injection (100 µg/tendon) in the peritendinous Achilles and received no treatment, LLLT (3 J, 810 nm, 100 mW), diclofenac (1.1 mg/kg), or dexamethasone (0.02 mg/kg). Histological analyses were performed at 10 time points up to 60 days (n = 5/group each time point), and included an assessment of the severity of inflammation, collagen fiber content, and organization. RESULTS: Collagenase injection induced a severe inflammatory reaction with significant reduction in collagen content for 48 h, and disorientation of collagen fibers lasting between 14 and 21 days. Diclofenac and dexamethasone reduced inflammatory signs during the first 2 days, although there was prolongation of the inflammatory phase and slower normalization of tendon quality, particularly in the dexamethasone group. LLLT prevented hemorrhage, reduced inflammation severity, and preserved tendon morphology compared with the other groups. CONCLUSIONS: LLLT showed a significant superiority over commonly used anti-inflammatory pharmaceutical agents in acute collagenase-induced tendinitis.

Steroid receptor antagonist mifepristone inhibits the anti-inflammatory effects of photoradiation.

OBJECTIVE: We designed an animal pleurisy study to assess if the anti-inflammatory effect of photoradiation could be affected by concomitant use of the cortisol antagonist mifepristone. BACKGROUND DATA: Although interactions between photoradiation and pharmacological agents are largely unknown, parallel use of steroids and photoradiation is common in the treatment of inflammatory disorders such as arthritis and tendinitis. METHODS: Forty BALB/c male mice were randomly divided in five groups. Inflammation was induced by carrageenan administered by intrathoracic injections. Four groups received carrageenan, and one control group received injections of sterile saline solution. At 1, 2, and 3 h after injections, photoradiation irradiation was performed with a dose of 7.5 J/cm(2). Two of the carrageenan-injected groups were pre-treated with orally administered mifepristone. RESULTS: Total leukocyte cell counts revealed that in carrageenan-induced pleurisy, photoradiation significantly reduced the number of leukocyte cells (p < 0.0001, mean 34.5 [95% CI: 32.8-36.2] versus 87.7 [95% CI: 81.0-94.4]), and that the effect of photoradiation could be totally blocked by adding the cortisol antagonist mifepristone (p < 0.0001, mean 34.5 [95% CI: 32.1-36.9] versus 82.9 [95%CI: 70.5-95.3]). CONCLUSION: The steroid receptor antagonist mifepristone significantly inhibited the anti-inflammatory effect of photoradiation. Commonly used glucocorticoids are also known to down-regulate steroid receptors, and further clinical studies are necessary to elucidate how this interaction may decrease the effect size of photoradiation over time. For this reason, we also suggest that, until further clinical data can be provided, clinical photoradiation trials should exclude patients who have received steroid therapy within 6 months before recruitment.

The effect of inhaled nitric oxide on the carrageenan-induced paw edema.

Inhaled nitric oxide therapy reaches not only pulmonary vessels, but also other vasculatures, presenting anti-inflammatory effects. Therefore, this study investigated the effects of inhaled nitric oxide on a mice model of carrageenan-induced paw edema. Paw edema was induced in male Swiss mice (20-30 g) by subplantar injection of carrageenan (0.05 ml of a 1% suspension in 0.9% saline). The evaluation of time-course edema (mililiter) was measured by plethysmometry until 12 h following carrageenan administration. Thirty minutes after carrageenan injection, some groups received inhaled nitric oxide (300 ppm at variable doses and times) or Indometacin (INDO 5 mg/Kg, v.o), while others received sildenafil (1 mg/Kg, i.p) or rolipram (3 mg/Kg, i.p.) with or without inhaled nitric oxide. Paws were assessed for edema levels by plethysmometry, mieloperoxidase activity and histological analysis. Inhaled nitric oxide significantly reduced carrageenan-induced paw edema, mieloperoxidase activity and inflammatory infiltrate, although similar results were also observed in sildenafil and rolipram treated groups. In addition, significant effects between inhaled nitric oxide with pharmacological therapy was observed. Inhaled nitric oxide presents anti-inflammatory effects on carrageenan-induce paw edema, as observed through reduced edema, mieloperoxidase activity and neutrophil infiltration, indicating that inhaled nitric oxide therapy goes beyond lung vascular effects.