Long term opioid use can induce persistent pain as an automatic adaptive response:
Because its main effect is mediated through the reward system, the brain undergoes several adaptations in response to repeated opioid use. For example, opioids can create pain as an adaptive counterbalancing effect (opponent effect) to pain relief while the opioid dose is active.52,53,62-65 As this opponent effect grows with continued long term opioid use, a broad physiological adaptation called allostasis resets the baseline pain experience to higher set points around which the pain/relief cycles fluctuate.52,53,65 Paired together, these phenomena are referred to as allostatic opponent effect. 52,53,65 Disability and suffering that includes anxiety, anger, irritability, depression, concentration problems, sleep problems, fatigue, and lethargy can also similarly increase as a part of the increasing allostatic opponent effect. 52,53,65 The clinical experience of worsening pain, suffering, disability, and overall health with psychiatric and medical instability due to opioid induced allostatic opponent adaptations may persist or worsen whether LTOT dose is continued, increased, decreased or discontinued.52,65 When this clinical picture emerges after discontinuation – also described as protracted withdrawal/abstinence syndrome – it may persist and even worsen for months or years after LTOT cessation or dose decrease due to persistence of allostatic adaptations.52,65-68 More detailed discussion of the allostatic opponent adaptations is provided in Appendix 1.