Chronic Pain | Complex regional pain syndromes

Complex regional pain syndromes (CRPS, reflex sympathetic dystrophy, causalgia) are painful neuropathic disorders that develop after trauma affecting a limb with (I) or without (II) nerve injury. Clinical features are pain, impairment of motor function, swelling and autonomic abnormalities (changes in sweating and blood flow). The International Association for the Study of Pain criteria for CRPS I include:

1. The presence of an initiating noxious event, or a cause of immobilization.
2. Continuing pain, allodynia, or hyperalgesia in which the pain is disproportionate to any inciting event.
3. Evidence at some time of edema, changes in skin blood flow, or abnormal sudomotor activity in the region of pain.
4. This diagnosis is excluded by the existence of conditions that would otherwise account for the degree of pain and dysfunction.

Although sympathetic influences are still viewed as the most likely mechanism underlying the development and/or perpetuation of CRPS, these influences are no longer ascribed to an increase in sympathetic tone. Rather, the most likely mechanism may be increased sensitivity to catecholamines due to sympathetic denervation with an increase in the number and/or sensitivity of peripheral axonal adrenoceptors. Several other pathophysiological mechanisms have been suggested, including neurogenic inflammation with the release of neuropeptides by primary nociceptive afferents and sympathetic efferents. These neuromediators, particularly substance P, calcitonin gene-related peptide, and neuropeptide Y (NPY), induce an inflammatory response (cutaneous erythema and edema) and lower the pain threshold. Neurogenic inflammation at the site of the lesion with neuromediator accumulation or depletion probably contributes to the pathophysiology of CRPS¹.

Treatment regimens for CRPS I vary widely and may include physical therapy, sympathetic nerve blocks, tricyclic antidepressants (TCAs), opiates, anticonvulsives, and psychologic treatment. In CRPS I, a prolonged regional inflammation may induce sensitization of primary and secondary somatosensory afferents (peripheral and central sensitization). These aspects of neuropathic pain may be present in each patient in a unique individual mix and with different time profiles and efforts should be made in aiming treatment at the dominant mechanisms underlying the regional inflammation and peripheral and/or central sensitization in an individual patient at a specific moment in time².

1. Pham T. Lafforgue P. Reflex sympathetic dystrophy syndrome and neuromediators. Joint, Bone, Spine: Revue du Rhumatisme. 2003: 70(1):12-7.

2. Ribbers GM, Geurts AC, Stam HJ, Mulder T.Pharmacologic treatment of complex regional pain syndrome I: a conceptual framework. Arch Phys Med Rehabil 2003;84:141-6.