title: Experimental characterization of the effects of acute stresslike doses of hydrocortisone in human neurogenic hyperalgesia models.
abstract: 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 stress-like 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.
authors.affiliation: Laboratory 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 Chair of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim, Ruprecht-Karls-University Heidelberg, Ludolf-Krehl-Str. 13-17, 68167 Mannheim, Germany.
authors.forename: Gilles P N
authors.initials: GPN
authors.lastname: Michaux
authors.forename: Walter
authors.initials: W
authors.lastname: Magerl
authors.forename: Fernand
authors.initials: F
authors.lastname: Anton
authors.forename: Rolf-Detlef
authors.initials: RD
authors.lastname: Treede
mesh_terms: D000208:Acute Disease; D000328:Adult; D000700:Analgesics / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone