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Experimental characterization of the effects of acute stresslike doses of hydrocortisone in human neurogenic hyperalgesia models

Michaux, Gilles P.N.a; Magerl, Walterb,*; Anton, Fernanda; Treede, Rolf-Detlefb

doi: 10.1016/j.pain.2011.10.043
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Summary A moderate dose of hydrocortisone reduced capsaicin-induced secondary hyperalgesia, but not pain to pinprick suggesting an antihyperalgesic action of glucocorticoids consistent with protection against maladaptive pain plasticity.

Relative hypothalamic-pituitary-adrenal axis dysfunction has been described as a common feature of several dysfunctional pain syndromes, and its end hormone cortisol may thus constitute a protective factor against the development of chronic pain. We investigated the potential influence of experimentally induced stresslike hypercortisolism on the induction of neurogenic hyperalgesia using 2 human surrogate models: secondary hyperalgesia after intradermal capsaicin injection into the volar forearm, and perceptual windup in normal skin. In a double-blind, placebo-controlled, randomized, crossover study, a psychophysical study was performed in 10 healthy subjects (median age 23 years) examining the effects of 40 mg orally administered hydrocortisone. Numeric pain ratings were assessed for punctate pinprick and light touch stimuli applied to the zone of secondary hyperalgesia adjacent to the capsaicin injection and to the contralateral control side. In addition, visual analog ratings were assessed for repetitive pinprick stimulation of the noninjected arm. Hydrocortisone significantly attenuated the late phase of capsaicin-induced pain by nearly 50%, and hyperalgesia to pinprick stimuli by 33% (both P < .05). Baseline mechanical pain and dynamic mechanical allodynia remained unaltered. Temporal summation (windup) to mechanical pain stimuli and electrically induced windup of second pain (tested in an independent cohort of 10 other subjects) were also unchanged. The selective effects of hydrocortisone on pinprick hyperalgesia but not pinprick pain suggest an antihyperalgesic rather than analgesic effect. The findings suggest that hypothalamic-pituitary-adrenal axis reactivity might be an important mechanism in resilience to dysfunctional pain syndromes.

aLaboratory of Psychophysics and Sensory Psychophysiology (LAPSE), Integrative Research Unit on Social and Individual Development (INSIDE), University of Luxembourg, 162A avenue de la Faïencerie, 1511 Luxembourg, Luxembourg

bChair of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim, Ruprecht-Karls-University Heidelberg, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany

*Corresponding author.

E-mail: walter.magerl@medma.uni-heidelberg.de

Submitted July 19, 2011; accepted October 31, 2011.

© 2012 Lippincott Williams & Wilkins, Inc.
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