Despite considerable progress in the field, the primary treatments for Osteoarthritis remain traditional. Existing medical treatments such as NSAIDs corticosteroids, and opioids mainly offer symptom relief without targeting the underlying causes of the condition. Although these drugs can provide temporary benefit, they are often associated with adverse effects like gastrointestinal, cardiovascular, and kidney complications, and opioids carry a risk of addiction. Moreover these treatments fall short in addressing the neuroinflammation and central pain sensitization that play a crucial role in the persistence and intensity of OA pain leaving many patients inadequately treated. In recent it has shown that in osteoarthritis there is activation of toll like receptor 4 or TLR4 in innate immune cells and further activation of NFkB pathway in leading to cytokine release and further damage. Low dose naltrexone or LDN represents a novel treatment strategy that targets both immune and nervous system pathways involved in chronic pain. In low doses, it briefly blocks opioid receptors, leading to a compensatory increase in the body’s natural opioid. Also dampen inflammation by inhibiting TLR4 and thereby suppressing microglial cell activity. This action decreases the production of inflammatory cytokines such as TNF alpha IL1beta and IL6 which are known to contribute to the development of osteoarthritis. LDN has demonstrated potential in managing various chronic pain and inflammatory conditions, with a favourable safety profile, low addiction risk and low cost. Its dual action on inflammation and nerve sensitization makes it a promising option for knee OA treatment. We hypothesise that LDN may act on TLR4 on peripheral innate immune cells and modulate the activity and decrease the pro inflammatory cytokines release in OA there for we propose this study.