CRPS Pain Studies For Brainiacs

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Greetings, Dear Reader.

Two noteworthy articles about CRPS were recently published in Pain: Journal of the International Association for the Study of Pain.

NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation
Volume 151, Issue 1, Pages 69-76 (October 2010)
S.M. Gustina, A. Schwarza, N. Birbaumer, N. Sines, A.C. Schmidt, R. Veit, W. Larbig, H. Flor, M. Lotze  [Corresponding author. Address: Functional Imaging Group, Center for Diagnostic Radiology and Neuroradiology, University of Greifswald, Friedrich-Löffler-Straße 23a, D-17487 Greifswald, Germany. Tel.: +49 3834 866899; fax: +49 3834 866898.]

Abstract
A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.

The second article is highly specialized and I cannot begin to unpack it.  The abstract is reproduced here for Serious Brainiacs.

Role of peripheral endothelin receptors in an animal model of complex regional pain syndrome type 1 (CRPS-I)
Volume 151, Issue 1, Pages 174-183 (October 2010)
Magali Millecamps, Andre Laferrière, J. Vaigunda Ragavendran, Laura S. Stone, Terence J. Coderre [Corresponding author. Address: Anesthesia Research Unit, McGill University, Room 1203, McIntyre Medical Bldg., 3655 Drummond St., Montreal, Quebec, Canada H3G 1Y6. Tel.: +1 514 398 5773; fax: +1 514 398 8241.]

Abstract
Chronic post-ischemic pain (CPIP) is an animal model of CRPS-I developed using a 3-h ischemia–reperfusion injury of the rodent hind paw. The contribution of local endothelin to nociception has been evaluated in CPIP mice by measuring sustained nociceptive behaviors (SNBs) following intraplantar injection of endothelin-1 or -2 (ET-1, ET-2). The effects of local BQ-123 (ETA-R antagonist), BQ-788 (ETB-R antagonist), IRL-1620 (ETB-R agonist) and naloxone (opioid antagonist) were assessed on ET-induced SNBs and/or mechanical and cold allodynia in CPIP mice. ETA-R and ETB-R expression was assessed using immunohistochemistry and Western blot analysis. Compared to shams, CPIP mice exhibited hypersensitivity to local ET-1 and ET-2. BQ-123 reduced ET-1- and ET-2-induced SNBs in both sham and CPIP animals, but not mechanical or cold allodynia. BQ-788 enhanced ET-1- and ET-2-induced SNBs in both sham and CPIP mice, and cold allodynia in CPIP mice. IRL-1620 displayed a non-opioid anti-nociceptive effect on ET-1- and ET-2-induced SNBs and mechanical allodynia in CPIP mice. The distribution of ETA-R and ETB-R was similar in plantar skin of sham and CPIP mice, but both receptors were over-expressed in plantar muscles of CPIP mice. This study shows that ETA-R and ETB-R have differing roles in nociception for sham and CPIP mice. CPIP mice exhibit more local endothelin-induced SNBs, develop a novel local ETB-R agonist-induced (non-opioid) analgesia, and exhibit over-expression of both receptors in plantar muscles, but not skin. The effectiveness of local ETB-R agonists as anti-allodynic treatments in CPIP mice holds promise for novel therapies in CRPS-I patients.