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