A cross-sectional survey assessing clinical utilization and physician perspectives on PEA-based therapy in the management of neuropathic pain
DOI:
https://doi.org/10.18203/issn.2455-4510.IntJResOrthop20262333Keywords:
Neuroinflammation, Chronic pain management, Prescribing patternsAbstract
Background: Neuropathic pain is a chronic condition associated with substantial morbidity and impaired quality of life. Palmitoylethanolamide (PEA), an endogenous lipid mediator with anti-inflammatory and neuroprotective properties, has emerged as a potential adjunctive therapy for neuropathic pain. This survey evaluated physicians’ utilization patterns, therapeutic positioning, perceived effectiveness, and safety of PEA-based formulations in routine clinical practice.
Methods: A descriptive, questionnaire-based cross-sectional survey was conducted among orthopedic surgeons attending IOACON-2025, Guwahati, India. A structured nine-item questionnaire was administered electronically, and responses from 93 physicians were analyzed using descriptive statistics.
Results: Most physicians reported frequent (49.5%) or very frequent (9.7%) prescribing of PEA-based formulations. Neuropathic pain (71.0%), chronic low back pain (60.2%), and peripheral nerve injury (57.0%) were the most common indications. More than half of the respondents (60.2%) initiated PEA-based therapy as an early adjunct to first-line treatment, while 26.9% prescribed it following an inadequate response to gabapentinoids. Overall efficacy was rated as highly effective by 24.7% and moderately effective by 69.9% of physicians. Symptom improvement was observed within 1-2 weeks by 40.9% of respondents and within 2-4 weeks by 30.1%. PEA-based formulations were considered highly or moderately effective in improving pain, burning sensation, tingling, paresthesia, and sleep disturbances by 94.6% of physicians. Most respondents (83.9%) reported excellent tolerability with minimal adverse effects. Once-daily dosing and improved patient compliance were identified as the most important factors influencing prescribing preference. Additionally, 94.6% considered PEA-based formulations suitable for routine or selective long-term maintenance therapy.
Conclusions: PEA-based formulations are widely utilized in clinical practice and are perceived by physicians as effective, well tolerated, and suitable for both adjunctive and long-term management of neuropathic pain. These findings support the growing role of PEA-based therapy in contemporary neuropathic pain management.
References
Van HO, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654-62.
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002.
Baron R. Neuropathic pain: a clinical perspective. Handb Exp Pharmacol. 2009;(194):3-30.
Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment. Lancet Neurol. 2010;9(8):807-19.
O'Connor AB. Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. Pharmacoeconomics. 2009;27(2):95-112.
McCarberg BH, Billington R. Consequences of neuropathic pain: quality-of-life issues and associated costs. Am J Manag Care. 2006;12(9):S263-8.
Doth AH, Hansson PT, Jensen MP, Taylor RS. The burden of neuropathic pain: a systematic review and meta-analysis of health utilities. Pain. 2010;149(2):338-44.
Finnerup NB, Kuner R, Jensen TS. Neuropathic pain: from mechanisms to treatment. Physiol Rev. 2021;101(1):259-301.
Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14(2):162-73.
Bouhassira D, Attal N. Translational neuropathic pain research: a clinical perspective. Neuroscience. 2016;338:27-35.
Ji RR, Donnelly CR, Nedergaard M. Astrocytes in chronic pain and itch. Nat Rev Neurosci. 2019;20(11):667-85.
Inoue K, Tsuda M. Microglia in neuropathic pain: cellular and molecular mechanisms and therapeutic potential. Nat Rev Neurosci. 2018;19(3):138-52.
Skaper SD, Facci L, Fusco M, Della Valle MF, Zusso M, Costa B, et al. Palmitoylethanolamide, a naturally occurring disease-modifying agent in neuropathic pain. Inflammopharmacology. 2014;22(2):79-94.
Gabrielsson L, Mattsson S, Fowler CJ. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016;82(4):932-42.
Paladini A, Fusco M, Cenacchi T, Schievano C, Piroli A, Varrassi G. Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician. 2016;19(2):11-24.
Cruccu G, Truini A. A review of neuropathic pain: from guidelines to clinical practice. Pain Ther. 2017;6(1):35-42.
Steels E, Venkatesh R, Steels E. Palmitoylethanolamide in the management of chronic pain and neuropathic symptoms: a systematic review. J Pain Res. 2019;12:2693-714.
Varrassi G, Pergolizzi JV, Paladini A, Taylor R, LeQuang JA, Gharibo C. A decades-long journey of palmitoylethanolamide (PEA) for neuropathic pain treatment. Drugs Context. 2025;14:2024-11.
Lang-Illievich K, Klivinyi C, Lasser C, Brenna CTA, Szilagyi IS, Bornemann-Cimenti H. Palmitoylethanolamide in the treatment of chronic pain: a systematic review and meta-analysis of double-blind randomized controlled trials. Nutrients. 2023;15(6):1350.
Scuteri D, Guida F, Boccella S, Palazzo E, Maione S, Rodríguez-Landa JF, et al. Effects of palmitoylethanolamide (PEA) on nociceptive, musculoskeletal and neuropathic pain: systematic review and meta-analysis of clinical evidence. Pharmaceutics. 2022;14(8):1672.
Wang Y, Duan X, Li Z, Pan Y, Deng J. Palmitoylethanolamide in the treatment of pain and its mechanisms: a review. Front Pharmacol. 2025.
Schweiger V, Schievano C, Martini A, Polati L, Del Balzo G, Simari S. Extended treatment with micron-size oral palmitoylethanolamide in chronic pain: a systematic review and meta-analysis. Nutrients. 2024;16(11):1653.
Prado MB, Nisce NRB, Cayanong EJB, Adiao KJB, Reyes MCD, Villa RL. Efficacy, safety, and tolerability of palmitoylethanolamide in neuropathic pain: systematic review and meta-analysis. J Diabetes Metab Disord. 2026;25(1):52.
Wang Y, Duan X, Li Z, Pan Y, Deng J. Palmitoylethanolamide in the Treatment of Pain and Its Clinical Application Prospects. Drug Des Devel Ther. 2025;19:6897-923.
Bortoletto R, Comacchio C, Garzitto M, Piscitelli F, Balestrieri M, Colizzi M. Palmitoylethanolamide supplementation for human health: a state-of-the-art systematic review of randomized controlled trials in patient populations. Brain Behav Immun Health. 2025;43:100927.