Opioid induced hyperalgesia (OIH): Some musings.
1/n: Pain experience includes sensory, affective/mood, and behavioral components, all of which are important. Sensory component can be triggered by nociceptive stimulus (peripheral injury), but not always (e.g. panic- chest pain).

2/n: OIH is a malfunction of nociceptive part of sensory component of pain experience (sensory + suffering- affective/mood + disability- behavioral). Opioid-induced pain escalation (OIPE), on the other hand, is a global effect that worsens all 3 components, not just nociceptive

3/n: The underlying biology of both OIH and OIPE is a fundamental behavioral effect of all addictive substances called the allostatic opponent effect.
https://en.wikipedia.org/wiki/Opponent-process_theory https://www.nature.com/articles/1395603

4/n: Opponent process: A substance use assoc. salient experience w/ an affective balance (e.g. pain/relief) is followed by an "opponent effect" (pain) after primary effect (relief). With long-term use, primary effect (relief) becomes weaker & opponent effect strengthens (pain)

5/n: 'Alloststaic reset': Physiological process by which physiological and functional stability (homeostasis) is achieved through change when the body exposed to chronic adverse environment (e.g. repeated opioid use). Body serially resets physiological 'normal' to adapt & survive

6/n: Allostatic opponent effect in opioid-related pain/relief: With long term opioid use, pain becomes the dominant experience after each opioid dose due to growing opponent effect. Allostatic neurophysiological system serially resets the baseline pain experience to higher levels

7/n: OIPE related to allostatic opponent effect is not typically responsive to dose escalation, but the individual still experiences a need for a higher dose as with opioid tolerance. So, it is separate from tolerance that responds to dose increase.

8/n: Neurobiological changes assoc. w/ established allostatic opponent effect is often hard to reverse and people can experience "protracted" withdrawal syndrome for months/years w/ opioid cessation or dose reduction, characterized by worsening pain and psychological instability.

9/n: So, allostatic opponent effect can make both long term opioid therapy and opioid tapering ineffective as both leads to worsening pain, suffering and disability. This is the #opioidconundrum.

10/n: Coming back to OIH: Allostatic opponent effect adversely influences all 3 components of pain experience; sensory, affective & behavioral (i.e. makes pain, suffering and disability worsen), and not just nociceptive part of the sensory experience.

11/n: Chronic pain is commonly a malfunction of the non-nociceptive components of pain experience. So, allostatic opponent effect associated with long term opioid use for chronic pain can be expected to cause pain escalation largely through non-nociceptive mechanisms

12/n: So, OIH, a nociceptive phenomenon, is often rare in long term opioid use whereas opioid-induced pain escalation (OIPE) is fairly common.

Caveat: This is the best theoretical explanation based on available science. Many parts of this explanation need data.