Complex Regional Pain Syndrome: More Than a Peripheral Disease

Abstract

SUMMARY At early stages, complex regional pain syndrome (CRPS) is clinically characterized by damage of peripheral tissues and nerves (edema, activation of osteoblasts, hyperalgesia to blunt pressure). These signs are the result of a dysbalance of pro- and anti-inflammatory cytokines, which normalizes approximately 6 months after the beginning of the disease, independent from clinical outcome. At the same time, evolving clinical signs such as allodynia, cold hyperalgesia, reduced tactile acuity or symptoms of disrupted body representation (e.g., neglect-like syndrome, impaired hand laterality recognition or shift of the body midline) suggest a crucial role of the CNS in the pathophysiology of this pain syndrome. Imaging studies have found a severe but reversible reduction of the cortical hand representation (primary and secondary somatosensory cortices and primary motor cortices). Interestingly however, complex multisensory integration in central association areas are unaffected in CRPS, as patients are capable of integrating artificial body parts or recognize 2D forms despite tactile dysfunction. Furthermore, despite its unilateral clinical manifestation, it has been shown that in CRPS but not in other unilateral neuropathic pain syndromes, alterations in cortical excitability occur bilaterally, both in sensory and motor regions. In conclusion, a more widespread and bilateral pattern of CNS reorganization appears to characterize CRPS, which might be related to dysfunctions in the basal ganglia or in thalamo-cortical structures. Consequently, CRPS treatment should involve not only anti-inflammatory measures and pain therapy, but also the integration of neurorehabilitative training programs.

Complex regional pain syndrome (CRPS) or continuous unilateral distal experimental pain stimulation in healthy subjects does not bias visual attention towards one hemifield

“…Although the exact mechanisms underlying CRPS are not fully known and may vary from individual to individual, it is generally accepted that besides the peripheral pathology, plastic processes of the central nervous system involving the pre-/frontal and cingulate cortex and including different sensory and motor areas of the brain are crucially involved Baron 2002, 2003;Maihöfner et al 2010;Reinersmann et al 2013;Schwarzer and Maier 2010;Wasner et al 2003). Brain areas involved in the processing of pain lie in the periaqueductal grey in the brainstem (Urban and Gebhart 1999), the medial thalamus (Fukumoto et al 1999), the primary and secondary somatosensory cortex (Juottonen et al 2002), and the insular and prefrontal cortex .…”

Basal ganglia dysfunction in complex regional pain syndrome – A valid hypothesis?

“…Previous studies concluded that CRPS is associated with a pathological cortical reorganization of sensory maps within the primary somatosensory cortex (Juottonen et al, 2002;Maihofner et al, 2006;Swart et al, 2009;Reinersmann et al, 2013;Pleger et al, 2014). Studies evaluating the functional neural networks in the brains of CRPS patients revealed widespread cortical functional connectivity changes (Maihofner et al, 2007;Bolwerk et al, 2013;Linnman et al, 2013).…”

Ameliorative potential of angiotensin-converting enzyme inhibitor (ramipril) on chronic constriction injury of sciatic nerve induced neuropathic pain in mice

“…22 Bradykinin is an endogenous nonapeptide which is catabolised by ACE. ACE inhibitors increase the level of bradykinin by reduction of catabolic action of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) . BK (1)(2)(3)(4)(5)(6)(7)(8)(9) produces the pain sensation by direct stimulation of nociceptors in the peripheral nervous system but this effect is of very short duration of action and its half-life is very short (15 seconds).…”

“…ACE inhibitors increase the level of bradykinin by reduction of catabolic action of BK (1)(2)(3)(4)(5)(6)(7)(8)(9) . BK (1)(2)(3)(4)(5)(6)(7)(8)(9) produces the pain sensation by direct stimulation of nociceptors in the peripheral nervous system but this effect is of very short duration of action and its half-life is very short (15 seconds). 23 In addition, BK (1)(2)(3)(4)(5)(6)(7)(8)(9) is not only degraded by ACE but also by other enzymatic pathways, i.e.…”

“…BK (1)(2)(3)(4)(5)(6)(7)(8)(9) produces the pain sensation by direct stimulation of nociceptors in the peripheral nervous system but this effect is of very short duration of action and its half-life is very short (15 seconds). 23 In addition, BK (1)(2)(3)(4)(5)(6)(7)(8)(9) is not only degraded by ACE but also by other enzymatic pathways, i.e. aminopeptidase P, carboxypeptidase, dipeptidyl peptidase IV, endothelin-converting enzyme, neprilysin, propyl oligopeptidase, and the neutral endopeptidase.…”