Facilitated neurogenic inflammation in unaffected limbs of patients with complex regional pain syndrome

Pain, edema, increased skin temperature, reddening and trophic changes characterize complex regional pain syndrome (CRPS). Recently, we have been able to show facilitated neurogenic inflammation on the affected limb. In the current study unaffected limbs were examined after resolution of the CRPS symptoms to assess possible generalized changes predisposing to CRPS. In 12 patients and in 12 healthy volunteers dermal microdialysis in combination with electrical C-fiber stimulation was employed to induce neuropeptide release. Dialysate protein concentration and axon reflex vasodilation were measured. Neither in patients nor in controls did electrical stimulation lead to protein extravasation, while axon reflex vasodilation was significantly enhanced even on the patients' unaffected limbs (P < 0.05). Our results support the hypothesis that facilitated neurogenic inflammation is a predisposing factor for CRPS. The lack of protein extravasation indicates that an initiating trauma is necessary to induce neuropeptide up-regulation in primary afferents.

[1]  S. Maier,et al.  Spinal Glia and Proinflammatory Cytokines Mediate Mirror-Image Neuropathic Pain in Rats , 2003, The Journal of Neuroscience.

[2]  Frank Birklein,et al.  Substance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome , 2003, Experimental Neurology.

[3]  Jan Klein,et al.  Evidence for local inflammation in complex regional pain syndrome type 1. , 2002, Mediators of inflammation.

[4]  R. Schwartzman,et al.  Abnormalities of cutaneous blood flow regulation in patients with reflex sympathetic dystrophy as measured by laser Doppler fluxmetry. , 1991, Archives of neurology.

[5]  R. Schwartzman,et al.  Reflex sympathetic dystrophy and causalgia. , 1992, Neurologic clinics.

[6]  M. Davies,et al.  Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation , 2001, Brain Research.

[7]  M. Davies,et al.  A substance P receptor (NK1) antagonist can reverse vascular and nociceptive abnormalities in a rat model of complex regional pain syndrome type II , 2003, Pain.

[8]  F. Sundler,et al.  Occurrence and distribution of neuropeptides in the human skin. An immunocytochemical and immunochemical study on normal skin and blister fluid from inflamed skin. , 1987, Acta dermato-venereologica.

[9]  C. Woolf,et al.  Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity , 1994, Neuroscience.

[10]  Ulf Lindblom,et al.  CLASSIFICATION OF CHRONIC PAIN , 2004 .

[11]  M. Schmelz,et al.  The important role of neuropeptides in complex regional pain syndrome , 2001, Neurology.

[12]  R. Rao,et al.  Interleukin-6 and nerve growth factor levels in peripheral nerve and brainstem after trigeminal nerve injury in the rat. , 2001, Archives of oral biology.

[13]  H. Merskey,et al.  Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the International Association for the Study of Pain, Subcommittee on Taxonomy. , 1994, Pain. Supplement.

[14]  E. Remarque,et al.  Innate cytokine profile in patients with complex regional pain syndrome is normal , 2001, Pain.

[15]  B. Neundörfer,et al.  Facilitated neurogenic inflammation in complex regional pain syndrome , 2001, Pain.

[16]  G. Wasner,et al.  Complex regional pain syndromes , 2001, Current pain and headache reports.

[17]  B. Roep,et al.  Susceptibility loci for complex regional pain syndrome , 2003, PAIN®.

[18]  A. Mailis,et al.  Profile of Caucasian Women with Possible Genetic Predisposition to Reflex Sympathetic Dystrophy: A Pilot Study , 1994, The Clinical journal of pain.