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Abstract: Normal hypothalamo-pituitary-adrenal axis function in a rat model of peripheral neuropathic pain

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www.ProHealth.com • May 12, 2005


Brain Res. 2005 May 24;1044(2):216-26. Epub 2005 Apr 13. Bomholt SF, Mikkelsen JD, Blackburn-Munro G. Department of Pharmacology, NeuroSearch A/S, 93 Pederstrupvej, DK-2750, Ballerup, Denmark; Department of Molecular Anatomy and Physiology, NeuroSearch A/S, 93 Pederstrupvej, DK-2750, Ballerup, Denmark. Chronic pain conditions such as rheumatoid arthritis and fibromyalgia are associated with profound hypothalamo-pituitary-adrenal (HPA) axis dysfunction which may exacerbate symptoms of chronic pain. HPA axis dysfunction has also been well documented in animal models of chronic inflammatory pain. However, the role of the HPA axis in animal models of neuropathic pain is currently unknown. Rats with a chronic constriction injury (CCI) of the sciatic nerve that developed marked mechanical allodynia and hyperalgesia of the injured hindpaw were used to determine basal and stimulatory levels of HPA axis activity. Plasma ACTH and corticosterone levels were increased significantly (P < 0.05) in CCI rats after 20 min restraint stress compared with baseline; however, the magnitude of the increase was no different from sham rats. Furthermore, the temporal profile of ACTH release over the 60 min period after termination of restraint was similar between CCI and sham rats suggesting normal glucocorticoid-mediated feedback. Restraint stress also significantly increased (P < 0.05) expression of the immediate early genes c-Fos and FosB within the hypothalamic PVN to a similar extent in CCI and sham rats. Within the parvocellular PVN basal expression of both CRF and AVP mRNA was no different between CCI and sham rats; restraint stress induced a significant 2.5 fold increase (P < 0.05) in CRF mRNA expression in sham rats only. These results suggest that, in contrast to inflammatory immune-mediated pain models where HPA axis function is profoundly altered, in the CCI model of neuropathic pain, basal HPA axis function is unchanged. Furthermore, the HPA axis responds normally to a novel stressor in the face of ongoing nociceptive input, a stimulus known to activate the HPA axis. PMID: 15885220 [PubMed - in process]




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