Proteolytic Enzymes As Adjuncts To Tramadol Therapy In Knee Osteoarthritis An Emerging Analgesic-Sparing strategy- a Review Article

Abstract

Knee osteoarthritis (KOA) is one of the most prevalent chronic musculoskeletal disorders and a major cause of pain, functional limitation, and reduced quality of life among the elderly population. Pharmacological management commonly includes nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioid analgesics such as Tramadol. Although tramadol is frequently prescribed for moderate to severe osteoarthritic pain, prolonged opioid use is associated with adverse effects, tolerance, dependence, and increased healthcare burden. Consequently, there is growing interest in analgesic-sparing strategies and opioid stewardship approaches that can optimize pain control while minimizing opioid exposure. Proteolytic enzymes including bromelain, trypsin, chymotrypsin, and serratiopeptidase have emerged as potential adjunctive agents due to their anti-inflammatory, anti-edematous, and analgesic properties. These enzymes may reduce inflammatory mediators, improve tissue healing, and enhance symptomatic relief in osteoarthritis. Recent evidence suggests that combining proteolytic enzymes with tramadol-based therapy may improve pain management outcomes, reduce analgesic requirements, and enhance tolerability. This review discusses the pathophysiology of knee osteoarthritis, the therapeutic role and limitations of tramadol, and the pharmacological basis of proteolytic enzyme therapy.Furthermore, it evaluates the current clinical evidence supporting the use of proteolytic enzymes as adjuncts to tramadol therapy and highlights their potential contribution to multimodal analgesia and opioid stewardship in osteoarthritis care.