Opioids’ Mechanism of action: Relief more than analgesia
The ideal goal of LTOT in chronic pain is sustained functional improvement and not just pain relief.46,47 As stated above, long-term opioids, like other “pain management” strategies, are presumed to increase function by providing sustained reduction in pain intensity (analgesia). However, opioids have much more complex effects than analgesia, and these effects tend to change with repeated opioid use and transform the chronic pain experience.
Opioids’ benefit is mediated primarily by their effect on the mu receptors –usually targeted by endogenous opioids–located in the reward system, reducing the emotional component of pain, and enhancing the relief experience. Less important are anti-nociceptive action of opioids on somatosensory pain pathways.48-51 The anti-nociceptive effect appears to be absent at lower opioid doses and emerges only at higher doses.48 So, many patients taking opioids can experience profound relief without a substantial reduction in pain intensity exemplified by an oft-heard quote, “The pain medications takes the edge off and I can do more, but the bad pain is still there.” Unlike many other analgesics, opioids provide added relief from comorbid psychological and physical suffering because pain relief and relief from psychologically distressing states like anger, anxiety, depression and PTSD and physically distressing states like insomnia and dyspnea share the same mechanistic pathways through the reward system.52,53 Clinical studies have shown that non-pain symptoms like depression and anxiety may have a larger influence than analgesia on opioid use and misuse among people on LTOT for chronic pain.54-57 Remarkably, up to 60% of the pain relief effect provided by opioid administration is related to its placebo effect mediated by the endogenous opioid system.58,59 Opioids can also enhance internal motivation for social functioning through their reward system action.60,61 In summary, opioids are not simple analgesics or pain medications, but complex distress relief medications that also provide relief from comorbid psychological and physical suffering, enhance placebo effects and allow improved functioning, but typically for limited time, on the order of 6-12 weeks