Looking for Responders among Women with Chronic Pelvic Pain Treated with a Comicronized Formulation of Micronized Palmitoylethanolamide and Polydatin

Abstract

Background. Palmitoylethanolamide is reported to solve pain and neuroinflammation in different models of chronic and neurodegenerative diseases. Some concerns have been illustrated for cautiously interpreting the available literature on the topic. Specifically, there is a lack of evidence about palmitoylethanolamide and female chronic pelvic pain. Concerns will be best solved by randomized trials. The present study was aimed at finding the best responders to micronized palmitoylethanolamide in female patient with chronic pelvic pain, using the existing literature at individual patient level, to help further randomized trial planning. Methods. After a systematic research, eligible studies (the ones enrolled female patients treated for chronic pelvic pain or for dyspareunia, dysuria, dyschezia, and dysmenorrhea with or without chronic pelvic pain) were assessed at individual patient data level. Conditional probabilities were calculated to assess variables conditioning the rates of good responders (pain score points more or equal to 3 reduction), poor responders (2 pain score reduction), and nonresponders at a three-month follow-up. Results. Only cases treated with palmitoylethanolamide comicronized with polydatin for a short period can be assessed. Good responders are more than 50%. In chronic pelvic pain, there is a 19.0% conditional probability to find good responders among patients with pain score at enrolment of 6 to 8 and of 6.8% to find poor responders among patients with a pain score at enrolment of 6 to 8. Painful disease does not matter on responders’ rates. Conclusion. Best responders to comicronized palmitoylethanolamide/polydatin are patients with pain score higher than 6 at enrolment, irrespective of other variables.

A Decades-Long Journey of Palmitoylethanolamide (PEA), as a Cornerstone in Chronic Neuropathic Pain Management: A Comprehensive Narrative Review

“…The utilization of combination medicines that exploit the synergistic effects between PEA and other drugs presents promising opportunities for improving therapeutic outcomes while simultaneously reducing adverse effects [47]. For instance, the combined administration of PEA and non-steroidal anti-inflammatory drugs (NSAIDs) can result in heightened pain alleviation, indicating a possible synergistic interplay for improved pain control [48]. This partnership demonstrates the potential to enhance treatment regimens by utilizing the synergistic advantages of PEA in conjunction with conventional analgesics.…”

ACOG Clinical Consensus No. 7: The Use of Cannabis Products for the Management of Pain Associated With Gynecologic Conditions

“…The studies demonstrated improvement in dysmenorrhea and dyspareunia, with few reported adverse effects. Based on the initial available evidence, more than 70% of patients with endometriosis or chronic pelvic pain may demonstrate some improvement with PEA therapy, with most reporting improvement after 3 months of use (35). It is important to note that most of these studies are limited by the lack of a control group and use of varying dosages.…”

Extended Treatment with Micron-Size Oral Palmitoylethanolamide (PEA) in Chronic Pain: A Systematic Review and Meta-Analysis

“…Although PEA is present in several dietary sources, its levels in foods are too low to represent an adequate intake in pathological conditions and a further exogenous supplementation must be considered [ 21 , 22 , 23 ]. However, exogenous PEA administration may significantly counteract neuroinflammation at the cellular level only in micronized (mPEA, 2–10 μm range) or ultra-micronized (umPEA, 0.8–6 μm range) forms, while in the native state (naïve PEA), due to the large particle size (from 100 up to 2000 μm range), PEA showed a poor absorption that significantly reduced its distribution and bioavailability, providing a low biological effect [ 23 , 24 , 25 , 26 ]. Also, it was demonstrated that mPEA and umPEA, in combination with natural compounds (co-micronized or co-ultra-micronized forms, respectively), such as the antioxidant polydatin (e.g., mPEAPol), demonstrated a synergistic effects and stronger biological activity [ 21 ].…”