Activation of Cutaneous Immune Responses in Complex Regional Pain Syndrome |
| |
| Affiliation: | 1. Department of Neurology, University Medical Center, Mainz, Germany;2. School of Psychology and Exercise Science, Murdoch University, Perth, Australia;3. Stanford University Department of Anesthesia, Palo Alto, California;4. Anesthesiology Service, VA Palo Alto Health Care System, Palo Alto, California;6. Physical Medicine and Rehabilitation Service, VA Palo Alto Health Care System, Palo Alto, California;1. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania;3. Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania;2. School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania;1. Centre for Research on Chronic Pain and Inflammatory Diseases, Murdoch University, Perth, Western Australia, Australia;2. Pain Management Research Institute, Kolling Institute, Northern Clinical School, The University of Sydney, NSW, Australia;3. Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia;1. Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia;2. Adynxx Inc, San Francisco, California;3. Department of Neurology, Drexel University, Philadelphia, Pennsylvania;4. Department of Neuroscience and Neurology, Albert Einstein College of Medicine, Bronx, New York;5. Celgene Corporation, Summit, New Jersey;7. Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;11. Department of Pathology (Neuropathology), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;12. Division of Pain Medicine, Johns Hopkins University, Baltimore, Maryland;8. Center for Clinical Research, Salem, North Carolina;1. Stanford University School of Medicine, Stanford University, Palo Alto, California;2. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;3. Feinberg School of Medicine, Northwestern University, Chicago, Illinois |
| |
| Abstract: | The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are elevated in experimental skin blister fluid from CRPS-affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS, exaggerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The current investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid. Skin biopsies were collected from the affected skin and the contralateral mirror site in 55 CRPS patients and the biopsy sections were immunostained for keratinocyte, cell proliferation, mast cell markers, TNF-α, and IL-6. In early CRPS, keratinocytes were activated in the affected skin, resulting in proliferation, epidermal thickening, and up-regulated TNF-α and IL-6 expression. In chronic CRPS, there was reduced keratinocyte proliferation, leading to epidermal thinning in the affected skin. Acute CRPS patients also had increased mast cell accumulation in the affected skin, but there was no increase in mast cell numbers in chronic CRPS.PerspectiveThe results of this study support the hypotheses that CRPS involves activation of the innate immune system, with keratinocyte and mast cell activation and proliferation, inflammatory mediator release, and pain. |
| |
| Keywords: | Complex regional pain syndrome pain immunology keratinocytes mast cells |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
