Published: 2 September 2015


Oxycodone — Sometimes More Pain than Gain?

Prescriber Update 36(3): 34
September 2015

Key Messages

  • Oxycodone use can result in increased sensitisation to pain (hyperalgesia).
  • Opioid-induced hyperalgesia (OIH) should be suspected if the patient experiences increased pain in the absence of disease progression that is not managed by increasing the oxycodone dosage.
  • If OIH is suspected, opioid reduction, opioid rotation or the use of an alternative pain-control may be required.

Healthcare professionals should be aware that the use of oxycodone can result in hyperalgesia.

The Centre for Adverse Reaction Monitoring (CARM) has received a report of a female patient who was receiving oxycodone for neuropathic pain (post juvenile idiopathic arthritis) reported a more intense pain that spread to involve her whole body. Her oxycodone dosage was increased in response. The patient was admitted to hospital where hyperalgesia was diagnosed. The patient was weaned off oxycodone and commenced on morphine. At the time of the report, the patient was improving.

Opioid-induced hyperalgesia (OIH) is a state of nociceptive (nerve cell) sensitisation caused by exposure to opioids whereby the patient receiving opioids for the treatment of pain may become more sensitive to pain1.

It is important to note that OIH and analgesic tolerance can both result in a similar effect on opioid dose requirements1. However, they are distinct pharmacologic phenomena1.Tolerance occurs when there is a progressive lack of response to a medicine resulting in increased dosage2. Tolerance can be overcome by increasing the medicine dosage. In contrast, OIH cannot be overcome by increasing the dosage.

OIH is thought to result from neuroplastic changes in the central nervous system and peripheral nervous system leading to sensitisation of pro-nociceptive pathways1.

OIH should be suspected if the opioid treatment effect wanes in the absence of disease progression, particularly if in association with unexplained pain or pain from ordinarily non-painful stimuli1.

If OIH is suspected, opioid reduction, opioid rotation or the use of a non-opioid strategy for pain control should be considered1–4.

The New Zealand data sheets for oxycodone lists the frequency of hyperalgesia as not known and includes the following precaution. “Hyperalgesia that will not respond to a further dose increase of oxycodone may very rarely occur in particular at high doses. An oxycodone dose reduction or change in opioid may be required3,4.

Healthcare professionals are encouraged to report any adverse events to the Centre for Adverse Reactions Monitoring (CARM). Reports may be submitted via the Medsafe website ( or by reporting directly to CARM (

  1. Chu LF, Angst MS, Clark D. 2008. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clinical Journal of Pain 24: 479–496.
  2. Silverman SM. 2009. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician 12: 679–684.
  3. BNM Group. 2014. Oxycodone (BNM) Data Sheet. 13 March 2014. URL: (accessed 22 July 2015).
  4. Mundipharma New Zealand Limited. 2014. Oxycontin Data Sheet. 2 October 2014. URL: (accessed 22 July 2015).
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