1. 2016;19;521-535Polyunsaturated Fatty Acids and Chronic Pain: A Systematic Review and Meta-analysis
   Systematic Review
   Bahi Takkouche, MD, PhD, Fatine Hadrya, PhD, and Jesus Prego-Dominguez, MSc.

BACKGROUND: Chronic pain is one of the most frequent disease symptoms and represents a global health problem with a considerable economic burden. The role of polyunsaturated fatty acids (PUFA) in chronic pain conditions was debated during the last decade with conflicting results.

OBJECTIVE: To assess whether polyunsaturated fatty acids intake is useful as a preventive or curative tool in chronic pain.

STUDY DESIGN: Systematic review and meta-analysis.

SETTING: This study examined all published studies, either preventive or curative, on PUFA supplementation and chronic pain.

METHODS: We retrieved studies published in any language by searching systematically Medline, Embase, Conference Proceedings Citation Index, dissertations databases, and the 5 regional bibliographic databases of the World Health Organization until May 2015.

We included both observational and intervention studies reporting effect measures and their confidence intervals of polyunsaturated fatty acids intake in the regular diet or supplementation and pain.

Two investigators selected studies; extracted data independently on baseline characteristics, exposure, and outcomes; and rated the quality of interventional studies using Jadad score.
We calculated pooled standardized mean differences (SMDs) of pain indexes such as the Visual Analogue Score. We further carried out subgroup analyses by disease, type of PUFA, outcome scale, quality index, dose, and time of supplementation.

RESULTS: We retrieved 5 observational and 46 intervention studies. Only one observational study showed a protective effect of PUFA. On the contrary, the interventional studies yielded a pooled random effects SMD of -0.40 (95% CI -0.58, -0.22), which indicates improvement, as 0 is the value that indicates absence of effect. The largest effect was found for dysmenorrhea (SMD -0.82, 95% CI -1.21, -0.43), ?-3 supplementation (-0.47, 95% CI -0.68, -0.26) and composite scores (-0.58, 95% CI -1.07, -0.09). Mitigation of pain was stronger for low doses (-0.55, 95% CI -0.79, -0.30) and short supplementation periods (-0.56, 95% CI -0.86, -0.25).

LIMITATIONS: While the number of curative studies was large, that of preventive studies available was limited.

CONCLUSION: Our results suggest that ?-3 PUFA supplementation moderately improves chronic pain, mainly that due to dysmenorrhea. Further investigation on the preventive potential of PUFA supplementation is needed, as the amount of evidence is scarce.

Key words: Meta-analysis, systematic review, chronic pain, PUFA, supplementation, ?-3, dysmenorrhea