Complex regional pain syndrome (CRPS) is an intractable condition associated with long-term pain and disability and detrimental effects on work, relationships and quality of life. Although many treatment approaches have been tried, at best they provide only limited benefits often at the cost of significant side effects. As CRPS is a chronic condition that requires ongoing treatment, an advance in treatment efficacy not only would decrease personal suffering but would also reduce the burden on over-stretched pain management services. Despite recent advances in clarifying early neuro-immune disturbances in CRPS, mechanisms that maintain chronic pain remain unclear. Unfortunately, this has hampered the development of effective treatment regimens for this debilitating disorder.
In complex regional pain syndrome (CRPS), hyperalgesia often extends beyond the CRPS-affected limb to encompass other sites on the ipsilateral side of the body. In addition, discomfort evoked by noise and light is greater on the ipsilateral than contralateral side and may exacerbate pain in the affected limb. These observations suggest that nociceptive processing is disrupted within the central nervous system in CRPS, and that this disruption involves sites of convergence of sensory and nociceptive pathways such as the thalamus and primary sensory cortices. We believe that this disruption is due, in part, to failure of ascending and descending inhibitory pain controls (e.g., in subcortical and spinal pathways regulated by the ipsilateral locus coeruleus).
In this project, electroencephalography (EEG) and pupillometry will be used to investigate neural mechanisms of pain modulation within the brainstem, thalamus and somatosensory cortex in real time in patients with CRPS. We will use this direct approach to explore whether failure of brainstem pain modulation processes to effectively regulate thalamo-cortical communication mediates hemilateral hyperalgesia.
Despite recent major advances in clarifying neuro-immune disturbances in CRPS, mechanisms that maintain pain remain unclear. From this perspective, identifying the source of sensory disturbances in CRPS is crucial because, once mechanisms are better understood, these mechanisms could be targeted to more effectively manage sensory disturbances and pain. The studies in this project will be the first to use advanced neurophysiological techniques to systematically examine subcortical processing of nociceptive stimuli in CRPS and to examine links with brainstem activation (reflected by pupillary responses) and pain. This study will help to clarify the source of sensory disturbances and pain in CRPS and, in turn, will encourage new approaches to treating this intractable complaint.
Dr Philip Finch, Professor Peter Drummond, Dr Hakuei Fujiyama, Murdoch University, WA, Dr Flavia Di Pietro, Curtin University, NSW.
The project was awarded $A65,323 through the ANZCA research grants program for 2022.