Palmitoylethanolamide, a Lipid Mediator, Improves Pain Scores in Diabetic Neuropathy

Treatment with palmitoylethanolamide (PEA) was found to result in decreased pain and improved sleep and mood among patients with diabetic peripheral neuropathy (DPN), according to the results of a study published in Inflammopharmacology.

This prospective, randomized, quadruple-blinded, placebo-controlled, parallel study was conducted at the University of Queensland in Australia. The study intervention, PEA, is an endogenous, biologically active lipid mediator that is part of the N-acylethanolamine family that is synthesized on demand by the phospholipid membrane of the cell. Patients (N=70) with DNP were randomly assigned in a 1:1 ratio to receive PEA 300 mg (n=35) or placebo (n=35) twice daily for 8 weeks. The primary outcomes were safety and efficacy, evaluated by change in scores on the Brief Pain Inventory Short Form for Diabetic Peripheral Neuropathy (BPI-DPN), a 4-item pain assessment tool.

The mean ages of patients in the intervention and control cohorts were 65.5 (range, 53-79) and 61.5 (range, 32-75) years, 60% and 40% were men, and average BMI values were 31.2 (range, 23.5-42.3) and 31.5 (range, 22.9-39.5) kg/m², respectively. The cohorts were well balanced at baseline with regard to the use of diabetic and analgesic medications. All but 3 patients had type 2 diabetes.

At baseline, average BPI severity scores were 4.77±1.45 in the PEA group and 4.96±1.37 in the placebo group. Recipients of PEA had a greater change from baseline in BPI severity scores compared with those receiving placebo at weeks 2 (change, -1.75 vs -0.80; P =.002), 4 (change, -2.28 vs -0.70; P <.001), 6 (change, -2.47 vs -0.42; P <.001), and 8 (change, -3.06 vs -0.77; P <.001), respectively.

At baseline, average BPI interference scores were 3.49±1.90 in the PEA group and 4.26±1.97 in the placebo group. Recipients of PEA had a greater change from baseline in BPI interference scores compared with those receiving placebo at weeks 4 (change, -1.04 vs -0.15; P =.001) and 8 (change, -1.90 vs -0.39; P <.001), respectively.

Similarly, at week 8 compared with baseline, recipients of PEA had greater improvement in Neuropathic Pain Symptoms Inventory (NPSI) total pain (P <.001), superficial pain (P <.001), paroxysmal pain (P <.001), paresthesia (P <.001), and deep pain (P =.002) scores, as well as Medical Outcomes Study sleep scale daytime somnolence (P <.001), sleep problem index (P <.001), sleep disturbance (P =.001), sleep adequacy (P =.001), and shortness of breath or headache (P =.04) scores compared with placebo.

Compared with placebo, the PEA intervention was also found to have a beneficial effect on interleukin-6 (P =.04) and C-reactive protein (P =.05) levels, as well as on BPI depression scores (P =.02).

Patients reported intermittent mild headache, constipation, urticaria, severe fatigue, and respiratory infection. No patients withdrew from the study due to an adverse event.

A major limitation of this study was the imbalance between participants with type 1 and 2 diabetes.

These data indicate that PEA reduced pain among patients with DNP with few safety signals and supported additional study of this intervention in the setting of DNP. The investigators conclude that “PEA was also well tolerated and reported to be safe as an adjunct in patients prescribed metformin and or insulin for the management of either type 1 or type 2 diabetes.”

Disclosure: This study was sponsored by Gencor Pacific Ltd. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.