Clinical Review Lesson of the week

Morphine induced allodynia in a child with brain tumourWhat is allodynia?

BMJ 1999; 319 doi: http://dx.doi.org/10.1136/bmj.319.7210.627 (Published 04 September 1999) Cite this as: BMJ 1999;319:627

Morphine induced allodynia in a child with brain tumour

  1. Sabine Heger, resident (S.Heger@rocketmail.com)a,
  2. Christoph Maier, associate professorb,
  3. Karin Otter, research assistantc,
  4. Ulf Helwig, residenta,
  5. Meinolf Suttorp, associate professora
  1. a Department of Paediatrics, Christian-Albrechts-University, 24105 Kiel, Germany
  2. b Department of Anaesthesiology, Christian-Albrechts-University
  3. c Department of Pharmacology, Christian-Albrechts-University
  4. BMJ
  1. Correspondence to: S Heger, Division of Neuroscience, Oregon Regional Primate Research Center, Oregon Health Sciences University, 595 NW 185th Avenue, Beaverton, OR 97066, USA
  • Accepted 21 January 1999

Hyperalgesia and allodynia induced by morphine can complicate treatment for pain in terminal care

Morphine is the drug of choice for patients with severe acute or chronic pain, especially those with intractable pain associated with malignant diseases. The drug is metabolised by the liver into morphine-3-glucuronide and morphine-6-glucuronide. The glucuronides are mainly eliminated via bile and urine.1 Morphine-6-glucuronide binds to opiate receptors and can be detected in the cerebral fluid after systemic administration; its analgesic effect is 40 times as potent as that of morphine itself.2 In contrast, morphine-3-glucuronide, which represents the major plasma and urinary metabolite of morphine, antagonises the effect of morphine and morphine-6-glucuronide.3

According to the World Health Organisation's recommendations for treatment of cancer pain, the morphine dose should be adapted to the individual patient. Therefore, if patients complain of an insufficient analgesic response to standard morphine dosage, they should receive higher doses, which may exceed hundreds of milligrams of morphine hourly.4 In a few adults treated with higher dosages for prolonged periods of time, morphine induced hyperalgesia or allodynia develops.5 6

Allodynia has been provoked in Sprague-Dawley rats. These animals are unable to metabolise morphine to morphine-6-glucuronide, and thus morphine-3-glucuronide is the major morphine metabolite. A noticeable inverse relation was observed between the mean degree of analgesia and ratio of plasma morphine-3-glucuronide to morphine.7 Consequently, a raised morphine-3-glucuronide to morphine-6-glucuronide ratio seems to be responsible for the phenomenon of hyperalgesia and allodynia.

There are only a few reports analysing the ratio of morphine and its metabolites in adult patients and children of various ages.810 Children metabolise morphine differently from adults, and the morphine-3-glucuronide to morphine ratio, in particular, is dependent on age. In addition, the plasma morphine-3-glucuronide to morphine-6-glucuronide ratio in children is half the ratio in …

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