title: Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism.
abstract: Clinical data have accumulated showing that relative hypocortisolism, which may be regarded as a neuroendocrinological correlate of chronic stress, may be a characteristic of some functional pain syndromes. However, it has not been clarified yet whether deregulations of the hypothalamus-pituitary-adrenal (HPA) axis may directly alter pain perception and thus be causally involved in the pathophysiology of these disorders. To test this hypothesis, we performed a randomized placebo-controlled crossover trial in N=20 healthy drug-free volunteers (median age 24yrs) and analyzed the effects of metyrapone-induced hypocortisolism on quantitatively assessed basal mechanical pain sensitivity (1.5-13m/s impact stimuli), perceptual wind-up (9m/s impact stimuli at 1Hz) and temporal summation of pain elicited by inter-digital web pinching (IWP; 10N pressure stimuli for 2min). Experimentally induced hypocortisolism significantly decreased pain detection thresholds and augmented temporal summation of IWP-induced pain (p<.05). The latter effect was dependent on the relative reduction in cortisol levels, and seemed to rely on a potentiated sensitization and not merely on the observed changes in basal pain sensitivity. Perceptual wind-up by contrast was reduced when cortisol synthesis was blocked (p<.05). This result is reminiscent of findings from animal studies showing a reversal of NMDA receptor activation by glucocorticoid receptor antagonists in neuropathic pain models. Our results speak in favor of a potential causal role of HPA axis alterations in pain chronicity.
authors.affiliation: Institute of Psychobiology, Department of Clinical Physiology, University of Trier, Johanniterufer 15, D-54290 Trier, Germany Laboratory of Psychobiology, University of Luxembourg, Campus Limpertsberg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
authors.forename: Linn K
authors.initials: LK
authors.lastname: Kuehl
authors.forename: Gilles P
authors.initials: GP
authors.lastname: Michaux
authors.forename: Steffen
authors.initials: S
authors.lastname: Richter
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schächinger
authors.forename: Fernand
authors.initials: F
authors.lastname: Anton
mesh_terms: D000328:Adult; D002908:Chronic Disease; D018592:Cross-Over Studies; D004700:Endocrine System Diseases / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D006930:Hyperalgesia / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D010465:Perception / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D006854:Hydrocortisone
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