Abstract
Opioids are regarded as among the most effective analgesic drugs and their use for the management of pain is considered standard of care. Despite their systematic administration in the peri-operative period, their impact on tissue repair has been studied mainly in the context of scar healing and is only beginning to be documented in the context of true tissue regeneration. Indeed, in mammals, growing evidence shows that opioids direct tissue repair towards scar healing, with a loss of tissue function, instead of the regenerative process that allows for recovery of both the morphology and function of tissue. Here, we review recent studies that highlight how opioids may prevent a regenerative process by silencing nociceptive nerve activity and a powerful anti-inflammatory effect. These data open up new perspectives for inducing tissue regeneration and argue for opioid-restricted strategies for managing pain associated with tissue injury.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Because naloxone methiodide (NalM) is a competitive antagonist of opioids, these results suggest that in control C57Bl6 mice, neutrophil reactive oxygen species (ROS) production is normally inhibited by endogenous opioids released at the injury site
Both the inflammatory response and nociceptive pathway activation collectively guide the outcome of tissue repair towards regeneration
Summary
Two opposite processes of tissue repair can occur: scar or regenerative healing. Adult mammals mainly show scar healing, some mammalian organs can really regenerate at embryonic and early postnatal stages [9,10,11,12,13,14] These observations have led to the hypothesis that inhibitory elements locking the regenerative process develop early after birth. Taking into account that (1) rapid and necessary activation of both immune and sensory nervous systems systematically follows tissue damage and (2) endogenous opioids release or medical treatment with opioids after tissue injury can minimize activation of both systems, this review provides evidence that immunosuppressive and analgesic effects of opioids inhibit the regeneration process. Endorphins, enkephalins, dynorphins, and nociceptins/orphanins represent the four families of endogenous opioids [22,23] They are peptides of varying length and are mainly synthesized and released by well-identified neuronal sub-populations located in the CNS [23]. Several signaling pathways can be initiated by activation of opioid receptors and take part in the cellular effects of opioids, ligand binding to these receptors mainly leads to inhibiting adenylate cyclase, preventing cAMP production and protein kinase A activation [28,29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
