Complex Regional Pain Syndrome – a centrally mediated condition?

Professor Peter Drummond

Complex Regional Pain Syndrome (CRPS) is often thought of as a peripheral condition with onset after injury (e.g. limb fracture, surgical procedure). The syndrome dates back at least to the American Civil War when neurologist Silas Weir Mitchell described the presentation of soldiers who developed severe neuropathic pain in a limb after low-velocity musket ball injuries. He coined the term, Causalgia.

Dr Philip Finch, Pain Specialist, South Perth

Not only did they present with severe ‘burning’ pain, florid autonomic symptoms and allodynia in the injured limb (excessive sensitivity to non-noxious stimuli), but also sensitivity to loud sounds (e.g. noise of a military band). Such symptoms have puzzled observers, leading to accusations of malingering or suggestions that the condition has a psychological aetiology. 

Whilst looking at the origins of the condition, Professor Peter Drummond and I decided to examine patients for evidence of central sensitisation and pain pathway modulation. 

Sensitivity in many sensory modalities (e.g. pressure, sharpness, light touch, warm and cold) is greater in the painful limb in people with CRPS. It was also greater on the entire affected side of the body. Sensitivity to sound (hyperacusis) and light (photophobia) in a group of people with CRPS and in people without pain was measured. Acuity for quiet sounds was unchanged. Tolerance for loud noise was lower in the CRPS group, particularly on the affected side. Loud noises made pain worse in both groups. 

Sensitivity to bright light was greater in the CRPS group than in people without pain, particularly on the CRPS side. Visual discomfort (photophobia) was found to be greater on the affected side. It appears that a ‘volume control’ mechanism for light, sound and pain may not function as well on the painful side. 

This provides some clues about brain pathways that may have changed in CRPS, which, in a sense, is good news in that we can consider a paradigm shift and possible new ways to best to manage the symptoms. 

Professor Drummond and I have now also studied more than 20 people with CRPS of a limb and a similar number of pain-free controls for changes in olfaction (mediated by olfactory nerve and trigeminal afferents). The responses to six different smells (some mildly confronting) were measured. In general, patients with CRPS in a limb find that the sense of smell is enhanced or altered on the right side if their CRPS is in a right-sided limb, but the results are not clear for left-sided CRPS. 

Our method involved testing the left nostril first and then the right. There was a surprise finding. 

Control subjects reported that odours presented to the second nostril (even with the sequence switched around) were stronger in intensity, suggesting a ramping-up of their ability to smell. The mechanism for this phenomenon is not clear. 

We have, therefore, had to redesign our experiments to test both nostrils at once by presenting odours to the midline, but in a random sequence. We intend retesting our long-suffering CRPS subjects using this new algorithm. The results, to date, are reasonably positive. Hopefully, further clarification will make it more compelling.

If our results are clearly positive, then we will have studied facial touch, hearing, visual response to bright light and now smell in CRPS patients. We sincerely hope that such results will give meaning to our patients reported alterations of these senses, and help disprove the contention by some that their reports are psychologically based or fanciful embellishments of their condition for financial or other gains.

Key messages
  • CPRS has a long history but remains poorly understood
  • Research suggests a possible central mechanism
  • If confirmed, this may change attitudes.

Author competing interests – the author has been involved in the research described