Discussion
OA, Pain, inflammation, osteoarthritis, arthritis, pain
DEGENERATION, ADVERSE EVENTS, INFLAMMATION, OSTEOARTHRITIS, ARTHRITIS, CHRONIC PAIN, DISEASES
The results of this randomized, double-blind, placebo-controlled study imply that oral supplementation with SPMs reduces pain and improves QoL in patients with symptomatic knee OA. While a placebo effect is observed in clinical variables, this is not as significant as the effect of SPMs consumption. Following a dose reduction from 2000 mg/day to 1000 mg/day from weeks 6 to 12, patients receiving oral supplementation with SPMs reported a statistically significant reduction in pain after 8 and 12 weeks of treatment compared to patients in the placebo group. Also, we observed a trend, such as the reduction in the pain VAS score up to week 12 and changes in VAS score from weeks 12 to 24, that added to the impact of continuous SPMs consumption. Altogether, these results support the recommended dual dose for OA patients.OA patients identify two types of pain: constant background pain and intermittent severe pain [Pain reduction associated with SPMs administration is in line with previous studies pertaining to inflammation resolution mechanisms. Preclinical data from different animal models of osteoarthritis, acute inflammatory pain, and chronic adjuvant-induced arthritis support the pain-relieving properties of 17-HDHA and resolvin D1 exogenous administration [To our knowledge, this is the first-in-human study evaluating possible residual effects of SPMs months after treatment. Our results do not support a long-lasting residual effect of SPMs consumption on chronic pain 12 weeks after the completion of treatment, suggesting the need for continuous supplementation to maintain clinical benefits. Preclinical studies, however, have evaluated the long-lasting effects of SPMs. A study in surgical pain in a mouse model demonstrated that intrathecal-injected resolvin D1 showed an analgesic effect for up to 30 days [Essentially, chronic pain involves central and peripheral neurological mechanisms. Preclinical studies have shown that SPMs administration dampens inflammatory pain [In this study, SPMs supplementation did not change concomitant, rescue, and anti-inflammatory medication use. Also, no adverse events related to supplementation nor any tolerability issues were reported in this study. These data support the favorable safety record of SPMs supplementation with the administered dose, which agrees with previous studies [Some limitations of this study included the modest sample size, which might have constrained the statistical significance of the results and masked the full clinical potential of SPMs consumption by OA patients. Despite the low number of participants, there is a general trend of improvement in most of the assessed clinical parameters, supporting the potential benefits to be confirmed in a larger sample number. Another limitation is the use of olive oil softgels as placebo. Olive oil has been reported to have clinical effects on OA patients, as previously reported in randomized controlled trials [One future study will involve the analysis of the biochemical parameters from plasma and serum samples of the patients on this study, including SPMs and cytokines. Other studies could be performed on assessing pain reduction in patient subpopulations. For example, studying the effect of SPMs consumption in patients with one specific degree of osteoarthritis according to the Kellgren and Lawrence classification. Patients with other diseases that also experience chronic pain may benefit from SPMs consumption, though; studies that support that need to be rigorously performed. As individual SPMs are made available in their purest forms, future studies could be performed to treat joint degeneration locally, instead of systemically.