Black and white image of an older gentleman resting head on right hand, eyes closed and appears in discomfort

If opioids are no longer working

In this step we will consider what to do if your patient’s pain is no longer responding to opioids.

Cancer progression

The most common reason for opioids to seemingly lose their effectiveness is the progression of the underlying cancer. This can result in new nociceptive (tissue damage) pain, which may respond to an increase in the opioid dose. If this dose increase is ineffective, this may be neuropathic pain.

Neuropathic (nerve) pain can occur if the tumour is compressing or invading neural tissue. This type of pain typically responds poorly to opioids and any benefits may be outweighed by side effects. Tramadol and tapentadol are opioids which inhibit norepinephrine/ serotonin reuptake and noradrenaline reuptake respectively. Theoretically these actions mean they could be of benefit in neuropathic pain but the evidence to support this is currently weak. In the UK neither of these drugs are recommended for the treatment of neuropathic pain in the non-specialist setting, although tramadol may be used for acute, rescue analgesia (NICE, 2018).

Opioid induced hyperalgesia

This should be suspected if the analgesic effect of an opioid is diminishing in the absence of disease progression. It is a paradoxical state of heightened sensitivity to pain due to long term exposure to opioids, the very treatment prescribed to alleviate it.

Our understanding of opioid induced hyperalgesia (OIH) is emerging. Its incidence and precise etiology is unknown, although several theories have been proposed. Another feature that suggests OIH is diffuse allodynia -that is, a painful sensation in response to non-painful stimuli such as light touch.

The mainstay of treatment for OIH is to reduce the opioid by gradually tapering the dose down. This may be difficult for patients to accept, particularly if their pain is, or has been, distressing. Specialist support is recommended.

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This article is from the free online course:

Opioid Analgesics: Treating Pain in People with Cancer

Newcastle University

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