Journal of Pain & Relief
Open Access

Abstract

Complex regional pain syndrome (CRPS) is a significantly disabling condition associated with a number of symptoms including severe limb pain. CRPS is one of the more challenging chronic pain conditions to treat successfully. Lack of adequate treatments for CRPS has resulted in part from incomplete understanding of its pathophysiologic mechanisms. We propose that different CRPS subtypes may result from facilitative or inhibitory influences exerted by the spinal-coeruleo-spinal pathway in three sites at the spinal cord: The dorsal horn (DH), intermediolateral cell column (IML) and ventral horn (VH). A facilitatory influence over DH may have a pronociceptive effect that explains exacerbated pain, sensory disturbances and spreading sensitization and neuroinflammation. For patients presenting with these symptoms, a descending inhibitory influence may provide pain relief. On the other hand, a facilitatory influence over preganglionic neurons located in IML cell column may increase sympathetic outflow with peripheral vasoconstriction, which leads to cold skin, ipsilateral limb ischaemia, and sympathetically maintained pain (SMP). For patients presenting with these symptoms, a descending inhibitory influence would be predicted to result in decreased sympathetic outflow and warm skin, as well as impairment of peripheral vasoconstrictor reflexes. Finally, a descending inhibitory influence over VH could explain muscle weakness and decreased active range of motion, while also facilitating motor reflexes, tremor and dystonia. The proposed model provides a mechanistically-based diagnostic scheme for classifying and explaining the sensory, autonomic and motor disturbances associated with CRPS syndrome, and it could provide the rationale for the development of novel and more effective treatments for CRPS.

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