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μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.
Two new studies show that mechanisms mediating the opioid side effects of tolerance, hyperalgesia and physical dependence are mediated spinally and can be dissociated from analgesia. These side effects can be selectively targeted by clinically available drugs without affecting their pain-relieving effects.
Neonatal abstinence syndrome refers to the signs and symptoms in a neonate that are caused by the cessation of prenatal exposure (via placental transfer) to various substances. In particular, opioid use or misuse during pregnancy can lead to neonatal opioid withdrawal syndrome.
Studies show that gut microbial dysbiosis induced by chronic opioid use is linked to central opioid tolerance. Here, we suggest that a persistent decrease in gastrointestinal motility by opioids is a primary cause of gut microbial dysbiosis and that improving gastrointestinal transit might be a strategy in preventing opioid analgesic tolerance.