Pathophysiology of complex regional pain syndrome

Complex regional pain syndrome (CRPS) most often follows injury to peripheral nerves or their endings in soft tissue. A combination of prostanoids, kinins and cytokines cause peripheral nociceptive sensitization. In time, the Mg(2+) block of the N-methyl-D-aspartate receptor is removed, pain transmission neurons (PTN) are altered by an influx of Ca(2+) that activates kinases for excitation and phosphatases for depression, activity-dependent plasticity that alters the firing of PTN. In time, these neurons undergo central sensitization that lead to a major physiological change of the autonomic, pain and motor systems. The role of the immune system and the sickness response is becoming clearer as microglia are activated following injury and can induce central sensitization while astrocytes may maintain the process.     

The fascination of complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a pain disorder involving the somatosensory, the somatomotor and the sympathetic nervous systems. Based on experiments conducted by Bove (2009), it is suggested that changes in impulse activity in small-diameter afferents and postganglionic axons generated by neuritis can contribute to signs of early CRPS. The potential mechanisms involved are discussed. These mechanisms include the possibility that CRPS, a disorder of the central nervous system, may be caused by a nerve inflammation.     

Pharmacotherapy options for complex regional pain syndrome

Complex regional pain syndrome is a painful disorder of unclear etiology, typically involving the distal part of one limb, represented by spontaneous and evoked pain as well as autonomic, motor and trophic abnormalities. It can be incapacitating and severely affect function and quality of life. Although full-blown complex regional pain syndrome can be diagnosed easily, less fulminate forms of the syndrome often remain undiagnosed. Controlled trials have demonstrated that a short course of oral corticosteroids, intranasal or intramuscular calcitonin, intravenous bisphosphonates, free-radical scavengers, gabapentin, regional intravenous sympathetic blocks with bretylium and spinal cord stimulation or physical therapy and occupational therapy can be efficacious for complex regional pain syndrome. Nonetheless, the management of this syndrome is difficult because currently available drugs and technologies do not provide adequate pain relief for a considerable percentage of sufferers. The present review focuses primarily on the pharmacotherapy of complex regional pain syndrome and describes briefly the epidemiology, pathogenesis and clinical manifestations of the syndrome.     

Motor cortex dysfunction in complex regional pain syndrome

ObjectiveMost patients with complex regional pain syndrome (CRPS) exhibit debilitating motor symptoms. The effect of continuous pain on motor system in CRPS, however, is not well known. We searched for signs of motor cortex dysfunction in chronic CRPS type 1 patients with motor impairment.MethodsWe recorded rhythmic brain activity with magnetoencephalography (MEG) during noxious thulium–laser stimulation of both hands in eight CRPS patients and eight control subjects. We measured excitability of the motor cortex by monitoring the reactivity of the ∼20-Hz motor cortex rhythm to laser stimuli. The reactivity was defined as a sum of the stimulus-induced suppression and the subsequent rebound of the ∼20-Hz rhythm.ResultsIn CRPS, the reactivity of the ∼20-Hz rhythm in the hemisphere contralateral to the painful hand was significantly weaker than in control subjects. The reactivity correlated with the mean level of the spontaneous pain (r = −0.64, P = 0.04). Suppression of the ∼20-Hz rhythm correlated with the grip strength in the painful hand (r = 0.66, P = 0.04).ConclusionContinuous pain in CRPS is associated with attenuated motor cortex reactivity.SignificanceAbnormal motor cortex reactivity may be linked with motor dysfunction of the affected hand in CRPS.     

Clinical features and pathophysiology of complex regional pain syndrome

A complex regional pain syndrome (CRPS)--multiple system dysfunction, severe and often chronic pain, and disability--can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS.     

Endothelial dysfunction in cold type complex regional pain syndrome

The authors examined endothelial function in cold type chronic complex regional pain syndrome (CRPS) I using acetylcholine- and sodium nitroprusside-induced vasodilation combined with laser Doppler flowmetry in 14 patients and 10 controls. On the affected side, acetylcholine-induced vasodilation was significantly reduced in comparison to controls and the unaffected extremity. No significant differences were found after application of sodium nitroprusside. The results demonstrate impaired endothelial function in chronic CRPS I.     

Abnormal movements in complex regional pain syndrome: assessment of their nature

Abnormal movements may be a clinical feature in complex regional pain syndrome (CRPS), but their basic nature is unclear. Between August 1989 and September 1998, patients fulfilling diagnostic criteria for CRPS (I or II) and displaying abnormal movements were entered into a prospective study. Fifty-eight patients, 39 women and 19 men, met entry criteria; 47 had sustained a minor physical injury at work. The patients exhibited various combinations of dystonic spasms, coarse postural or action tremor, irregular jerks, and, in one case, choreiform movements. Patients underwent rigorous clinical and laboratory evaluation aimed at characterizing their neurological disturbance. Surprisingly, no case of CRPS II but only cases of CRPS type I displayed abnormal movements. In addition to an absence of evidence of structural nerve, spinal cord, or intracranial damage, all CRPS I patients with abnormal movements typically exhibited pseudoneurological (nonorganic) signs. In some cases, malingering was documented by secret surveillance. This study highlights abnormal movements in CRPS as constituting a key clinical feature that differentiates CRPS I from CRPS II. They are consistently of somatoform or malingered origin, signaling an underlying psychoneurological disorder responsible for the entire CRPS profile.