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EMERGING TREATMENT AND DIAGNOSIS EMERGING TREATMENT AND DIAGNOSIS 58 | T H E PA I N P R A C T I T I O N E R | S P R I N G 2 0 0 6
FEATURE | COMPLEX REGIONAL PAIN SYNDROME Neuroimmunologic Approaches to Emerging and Potential Therapies for Complex Regional Pain Syndrome (CRPS) BY DONALD C. MANNING, MD, PhD Despite a great deal of progress in defining Complex Regional Pain Syndrome (CRPS), there is still controversy regarding the mechanisms involved. THEORIES HAVE INCLUDED INFLAMMATION, neuropathic mechanisms, ischemic injury and abnormal sympathetic nervous system function. To date there is no approved treatment for CRPS, and therapies for neuropathic or inflammatory pain have given disappointing results, affording many patients only partial relief at best (1). Therefore, it is time for a reevaluation of CRPS mechanisms to enable new therapeutic opportunities. The high female predominance (75%) and the combination of inflammatory and neuropathic pain components could be consistent with an autoimmune mechanism. Targeting therapies toward immune activation involving cytokines, glia, or the infiltration of immune cells is a new approach for pain therapy, although it has already been employed with some success in oncology and rheumatology. Neuroimmune activation involves a bidirectional stimulation of neurons and immune cells in response to trauma or inflammation (2). Immune cells release inflammatory [e.g., cytokines tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6] and anti-inflammatory (e.g., cytokine IL-10) molecules and they, in turn, are modulated by neurotransmitters, especially the sympathetic nervous system transmitter norepinephrine (3,4). Cytokines are polypeptides that can act locally, within tissues, or at a distance similar to hormones. They regulate replication, development and activation of cells in the immune, nervous and hematopoetic systems. The biology of the cytokines is complicated in that different cells can produce the same cytokine that can in turn have different effects or different cytokines can have similar effects or antagonize each other depending upon the local environment. Cytokines as Chronic Pain Mediators TNF, IL-1 AND IL-6 are the cytokines with the best-documented pathological roles in neuropathic pain. In healthy animals, the administration of IL-1 or TNF alone can produce symptoms of neuropathic pain. Spinal neuron activation by these cytokines can produce long-term alterations in neuronal excitability. Activation of non-neuronal glial cells with extensive interconnections within the spinal cord could account for central cytokine release (5) as well as the spread of excitation beyond traditional neuroanatomical boundaries and reactivation of the pain system after new injuries (6). Infusion of IL-1 or TNF for adjuvant cancer chemotherapy has been associated with an incidence of nearly 50% of pain syndromes or complaints of pain and tenderness at the injection site (7-9). Whereas TNF and IL-1 play important roles in the T H E PA I N P R A C T I T I O N E R | V O L U M E 16 , N U M B E R 1 | 59
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EDITORS’ CORNER | COMPLEX REGIONA
Page 8 and 9: EDITORS’ CORNER | COMPLEX REGIONA
Page 10 and 11: COMMENTARY | GIORDANO Comprehending
Page 16 and 17: FEATURE | BROATCH RSDSA: Expanding
Page 18 and 19: FEATURE | BROATCH We are acutely aw
Page 20 and 21: FEATURE | BROATCH information, such
Page 22 and 23: FEATURE | PATIENT PROFILE PEOPLE WI
Page 24 and 25: PEOPLE WITH CRPS | THEIR STORIES AN
Page 26 and 27: PEOPLE WITH CRPS | THEIR STORIES AN
Page 32 and 33: FEATURE | GALER 32 | T H E PA I N P
Page 34 and 35: FEATURE | GALER TABLE 1 | IASP Diag
Page 36 and 37: FEATURE | GALER Although there is s
Page 38 and 39: FEATURE | GALER 10. Gammaitoni A, G
Page 40 and 41: INTERVIEW | COVINGTON LIFEBOAT mixe
Page 42 and 43: INTERVIEW | COVINGTON Q. Have any s
Page 45 and 46: Reap the Rewards of Membership Beco
Page 47 and 48: with depression. However, they foun
Page 49 and 50: It is common for patients in pain i
Page 51 and 52: There are multiple forms of amplifi
Page 53 and 54: Okay for Vegas. Not your Practice.
Page 55 and 56: especially opioids. Opioids should
Page 57: Subscribe to Currents Today! The Ac
Page 61 and 62: FEATURE | COMPLEX REGIONAL PAIN SYN
Page 63 and 64: ZICONOTIDE: Promising New Treatment
Page 65 and 66: UNRIVALED INDEPENDENCE COMING SOON
Page 67 and 68: D O YO U G E T I T ? Subscribe to T
Page 69 and 70: SCS as Part of the CRPS Treatment A
Page 72 and 73: OPINION | GETSON The Use of Thermog
Page 74 and 75: IN CONCLUSION | MOSKOVITZ A Theory
Page 76 and 77: IN CONCLUSION | MOSKOVITZ even thin
Page 78 and 79: IN CONCLUSION | MOSKOVITZ Comorbidi
Page 80 and 81: IN CONCLUSION | MOSKOVITZ empathy e
Page 82 and 83: AC ADEMY NEWS | AMERICAN ACADEMY OF
Page 84 and 85: CL ASSIFIED ADS & DIRECTORY | AMERI
Page 86 and 87: RESOURCES | CRPS RESOURCES FOR CRPS
Page 88: A m e r i c a n A c a d e m y o f P
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