When morphine hurts MEDECIN ABONNE

We must first define hyperalgesia and allodynia, primary and secondary hyperalgesia:

  • Hyperalgesia: for a given painful stimulus, the painful sensation is abnormally increased
  • Allodynia: a normally non-painful sensation becomes painful.
  • Primary hyperalgesia: it is a local peripheral hyperalgesia generally linked to the inflammatory “soup” accompanying tissue damage.
  • Secondary hyperalgesia: this is hyperalgesia of central origin linked to cerebral or spinal cord dysfunction in the control of the nociceptive message.

An example of a clinical case

Mrs. X, 45 years old, was operated on for right carpal tunnel syndrome 2 years ago.
She has no notable history. She regularly practiced physical activity (several jogging per week). She also did not present any particular problem with her work (office work).
Following this surgery, she will present with shoulder-hand syndrome (CRPS type 1) which will cause significant pain and functional discomfort in her right arm. After 6 months, the absence of favorable evolution, and a progressive worsening of the pain, she will benefit from opioid treatment with oxycodone at a dose of 20 mg morning and evening (Oxycontin 20 mg) with interdoses of ‘Oxynorm 5 mg if necessary up to 4 times a day.
In the weeks that follow (Mm X doesn’t remember exactly how many) diffuse pain will appear.
On clinical examination we found a patient with diffuse muscular pain, allodynia when touched by the skin which was also diffuse.
Given her history and a strong suspicion of secondary hyperalgesia, Ms.
Mrs. A week after this first consultation, Mm. She no longer has any pain…. There persists a small reduction in the amplitude of mobilization of her non-painful right shoulder, the after-effects of her shoulder-hand syndrome.

Pathophysiology of secondary hyperalgesia

Morphine receptors

See this article

Pain regulation and morphine

Opioids stimulate an anti-nociceptive but also pronociceptive system. It is the balance between these two systems that determines the effect of opioids:

Hyperalgesia scheme

The balance between the two systems is complex. When the pronociceptive system becomes predominant, hyperalgesia and/or allodynia sets in. The system can shift more towards hyperalgesia if the patient suffers from chronic pain. This allodynia is suppressed by ketamine (anti NMDA).
Note that when the patient is on morphine a phenomenon of tolerance is added by phosphorylation of opioid receptors and internalization of the latter in such a way that in certain cases the Gs proteins become predominant and promotes nociception and secondary hyperalgesia.

Description of secondary hyperalgesia induced by opioids

Appearance of diffuse pain with increase in pain already present
Diffuse muscle pain is noted, pain on cutaneous stimulation
The pain is increased by interdoses of morphine.

Note that the more powerful the opioid and the faster its release rate, the greater the probability of developing secondary hyperalgesia. For example the use of fentanyl pods in non-cancer pain situations.

It should be noted that patients with chronic pain have a favorable situation for developing this phenomenon.

Treatment

  • Reduction of morphine doses
  • Ketamine treatment
  • Opioid rotation helps improve the situation
  • Sometimes opioid withdrawal is necessary
Post operative chronic pain