Opioid-induced hyperalgesia: is it a clinically relevant phenomenon?

Int J Pharm Pract. 2022 Nov 4;30(5):479-483. doi: 10.1093/ijpp/riac031.

Abstract

The potential for the development of opioid-induced hyperalgesia (OIH) provokes debate about whether long-term treatment with opioids is advisable and effective. If OIH develops during acute administration, will continuation of opioids actually make the pain worse? Hence, it is not surprising that OIH is part of the rationale used to promote deprescribing opioids in patients with chronic pain. But is there evidence that OIH is a clinically relevant phenomenon? This Commentary examines the evidence for OIH in randomized clinical trials in both the acute and chronic settings. Of critical importance in such an assessment is a trial design capable of differentiating OIH, tolerance, withdrawal-mediated pain sensitivity and worsening of the disease. However, studies published to date that purport to give evidence of OIH via experimentally induced pain all lack the rigour needed to differentiate these phenomena. Patient-reported measures of pain and analgesic consumption in these trials are not consistent with the presence of clinically significant OIH. At present, there is insufficient evidence from well-designed clinical trials that OIH is a clinically relevant phenomenon. Hence, while there are other reasons to avoid long-term use of opioids, the potential for the development of hyperalgesia during chronic opioid treatment is not a sound rationale for deprescribing these drugs in patients with chronic pain.

Keywords: fentanyl; opioid-induced hyperalgesia; remifentanil; tolerance; withdrawal pain.

MeSH terms

  • Analgesics, Opioid* / adverse effects
  • Chronic Pain* / drug therapy
  • Drug Tolerance
  • Humans
  • Hyperalgesia* / chemically induced
  • Hyperalgesia* / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Analgesics, Opioid