Role of Tumor Necrosis Factor Alpha (TNF-α) in Opioid Withdrawal Syndrome

Abstract

Opioids are powerful pain relievers; use of opioids for the treatment of pain has been associated with the potential disadvantages including development of tolerance, dependence. Drug addiction represents one of the major medical, social and economic burdens of human behavior. Various pathways and cytokines are involved in opioid withdrawal. The cytokine, tumour necrosis factor-alpha (TNF-α) plays a key role in the pathogenesis of many chronic inflammatory diseases and its increased level also caused withdrawal syndrome. Glial celss also play important role in opioid withdrawal. Identification of glial-mediated mechanism inducing opioid side effects includes cytokine receptor, κ-opioid reepor, NMDA receptor and toll like receptor (TLR). Glial activation through TLR leading to the release of proinflammatory cytokines (TNF-α) acting on neurons which is important in the complex syndrome of opioid dependence and withdrawal. Moreover, agents targeting the TNF-α such as AV411, thalidomide and rdp58, all show varied but promising files for providing significant relief from opioid side effects.