Published: 3 June 2021

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The paradox of opioid-induced hyperalgesia

Published: 3 June 2021
Prescriber Update 42(2): 27–28
June 2021

Opioids are generally indicated for treatment of moderate to severe acute pain and for cancer pain. They are not recommended for chronic non-cancer pain due to concerns over the long-term efficacy and safety of treatment, including the risk of abuse, misuse and dependence.^1,2

Multiple adverse events are associated with long-term opioid therapy, including opioid-induced hyperalgesia.² At a recent Medicines Adverse Reactions Committee meeting, the Committee recommended highlighting this condition to prescribers.³

Opioid-induced hyperalgesia (OIH)

Long-term use of opioids can paradoxically induce or sensitise patients to acute pain, a condition called ‘opioid-induced hyperalgesia’ (OIH).² The type of pain experienced might be the same as or different from the original underlying pain,² and in some cases, patients may experience pain from ordinarily non-painful stimuli (allodynia).⁴ The development of OIH may explain the loss of treatment efficacy in some patients.²

In preclinical laboratory settings, OIH is a well-established, easily reproducible state of nociceptive sensitisation caused by exposure to opioids.⁴ However, there is limited evidence for the existence of OIH in patients with chronic non-cancer or cancer-related pain.⁵ A recent systematic review concluded that OIH was evident in patients after chronic opioid exposure, but that the findings were dependent on both the pain stimulus and assessment measures.⁶

OIH is not opioid tolerance

Opioid tolerance is characterised by decreasing efficacy of the opioid, which can be overcome by increasing the dose.^2,5 Pain is usually limited to its original site and improves in response to opioid dose escalation.⁵ In contrast, OIH refers to reduced pain tolerance. OIH may present as either increased clinical pain, diffuse allodynia not associated with the original pain, or both, which worsen in response to increasing the opioid dose.^2,5

Management

Suspect OIH when an opioid treatment’s effect seems to wane in the absence of disease progression or the patient experiences increased levels of pain with increasing opioid dosages.² The patient may also report unexplained pain or diffuse allodynia not associated with the original pain.²

Re-evaluate pain management strategies if OIH is suspected. This may include non-pharmacological pain treatment, patient education, reducing the opioid dose or changing to a different opioid.⁴ Follow local guidelines, including referral to a pain specialist team where available.¹

References

1. New Zealand Formulary (NZF). 2021. NZF v106: Opioid analgesics 1 April 2021. URL: nzf.org.nz/nzf_2456 (accessed 12 April 2021).
2. Lee M, Silverman S, Hansen H, et al. 2011. A comprehensive review of opioid-induced hyperalgesia. Pain Physician 14(2): 145-61. URL: painphysicianjournal.com/current/pdf?article=MTQ0Ng%3D%3D&journal=60 (accessed 12 April 2021).
3. Medsafe. 2020. Minutes of the 184^th Medicines Adverse Reactions Committee Meeting 3 December 2020. URL: medsafe.govt.nz/profs/adverse/Minutes184.htm (accessed 12 May 2021).
4. Portenoy R, Mehta A and Ahmed E. 2021. Prevention and management of side effects in patients receiving opioids for chronic pain. In: UpToDate 6 January 2021. URL: uptodate.com/contents/prevention-and-management-of-side-effects-in-patients-receiving-opioids-for-chronic-pain (accessed 12 April 2021).
5. Eisenberg E, Suzan E and Pud D. 2015. Opioid-induced hyperalgesia (OIH): a real clinical problem or just an experimental phenomenon? Journal of Pain and Symptom Management 49(3): 632-6. DOI: https://doi.org/10.1016/j.jpainsymman.2014.07.005 (accessed 12 April 2021).
6. Higgins C, Smith B and Matthews K. 2019. Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure: a systematic review and meta-analysis. British Journal of Anaesthesia 122(6): e114-26. DOI: https://doi.org/10.1016/j.bja.2018.09.019 (accessed 7 April 2021).