title: Experimental hypoglycemia is a human model of stress-induced hyperalgesia.
abstract: Hypoglycemia is a physiological stress that leads to the release of stress hormones, such as catecholamines and glucocorticoids, and proinflammatory cytokines. These factors, in euglycemic animal models, are associated with stress-induced hyperalgesia. The primary aim of this study was to determine whether experimental hypoglycemia in humans would lead to a hyperalgesic state. In 2 separate 3-day admissions separated by 1 to 3 months, healthy study participants were exposed to two 2-hour euglycemic hyperinsulinemic clamps or two 2-hour hypoglycemic hyperinsulinemic clamps. Thermal quantitative sensory testing and thermal pain assessments were measured the day before and the day after euglycemia or hypoglycemia. In contrast to prior euglycemia exposure, prior hypoglycemia exposure resulted in enhanced pain sensitivity to hot and cold stimuli as well as enhanced temporal summation to repeated heat-pain stimuli. These findings suggest that prior exposure to hypoglycemia causes a state of enhanced pain sensitivity that is consistent with stress-induced hyperalgesia. This human model may provide a framework for hypothesis testing and targeted, mechanism-based pharmacological interventions to delineate the molecular basis of hyperalgesia and pain susceptibility.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Gibbons
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.forename: Istvan
authors.initials: I
authors.lastname: Bonyhay
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D015309:Glucose Clamp Technique / Q000009:adverse effects*; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007003:Hypoglycemia / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000009:adverse effects; D007328:Insulin / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D017288:Pain Threshold / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin