Analgesic Efficacy of Pre-Operative Dose of Palmitoylethanolamide in Patients Undergoing Total Knee Arthroplasty, A Randomized Double-Blinded Controlled Trial.

Elective total knee arthroplasty (TKA) is the gold standard for management of arthritis-associated pain and disability in osteoarthritis patients who have failed non-operative treatment modalities Following TKA, patients experience severe pain mediated by multiple pathways Painful stimuli to the body are detected by the free endings of peripheral nerves called nociceptors . Pre-emptive analgesia is analgesia given before the onset of painful stimuli to prevent central sensitization of nervous system to subsequent stimuli that could increase pain Studies have shown that pre-emptive analgesia reduce immediate postoperative pain and also prevent the development of chronic pain by decreasing altered sensory processing .

Multi-modal analgesia is the rational approach to pain management since no single analgesia targets all types of pain

. Increasing evidence has shown that neuro-inflammation plays a key role in pain progression which is sustained by an imbalance within pro-inflammatory and pro-resolving mediators Acylethanolamines (NAEs) are a family of endogenous bio active lipids that regulate multiple processes including pain and inflammation . One of the most widely studied NAEs is the analgesic endocannabinoid compound, palmitoylethanolamide (PEA). Previous research has demonstrated the effectiveness of PEA on conditions characterized by chronic and/or neurological pain The aim of the study is to investigate the safety, tolerability and efficacy of doses of PEA on symptoms of post operative pain.