Dexamethasone-suppressed Salivary Cortisol and Pain Sensitivity in Female Twins.
Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with chronic pain. Studying pain sensitivity and the HPA axis could elucidate the role of stress in chronic pain development, which might be influenced by familial factors, including genes.



Associations between pain sensitivity and salivary cortisol and familial confounding in these associations were examined in 88 female, community-based twin pairs (75% monozygotic, mean age 29 y). Cortisol was assessed after 0.25 mg dexamethasone (DEX), recovery from 0.25 mg DEX, and after 0.5 mg DEX. Cold pressor task (CPT) pain ratings were obtained at threshold and at tolerance. Conditioned pain modulation (CPM) was examined using thermal heat as the testing stimulus and hot water as the conditioning stimulus. Generalized estimating equation models were used and adjusted for baseline pain rating, age, and other relevant covariates.



After controlling for baseline cortisol, greater cortisol suppression following DEX administration and lower recovery cortisol levels were associated with higher pain ratings at tolerance during the CPT (Bs=-2.42 to -17.82; Ps=0.031 to<0.001) as well as with reduced CPM (Bs=-0.92 to -1.68; Ps=0.003 to 0.046). Interestingly, familial confounding was evident in the CPT and CPM during recovery from DEX administration, but not immediately following DEX administration.



These findings contribute to understanding possible mechanisms underlying chronic pain by demonstrating that HPA axis response to negative feedback is related to pain sensitivity.
*San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology †VA Center of Excellence for Stress and Mental Health **Department of Psychiatry, University of California, San Diego, San Diego, CA Departments of ‡Psychiatry and Behavioral Sciences #Epidemiology and Medicine, University of Washington, Seattle, WA §VA Puget Sound Healthcare System, Seattle Division, Seattle, WA ¶Elson S. Floyd College of Medicine, Washington State University, Seattle and Spokane, WA ∥Department of Medicine, Division of Rheumatology & Immunology, Vanderbilt University, Nashville, TN.
Kathryn M
KM
Godfrey
Matthew
M
Herbert
Eric
E
Strachan
Sheeva
S
Mostoufi
Leslie J
LJ
Crofford
Dedra
D
Buchwald
Brian
B
Poeschla
Annemarie
A
Succop
Niloofar
N
Afari
D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D003080:Cold Temperature; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D011312:Pressure; D012042:Registries; D012463:Saliva / Q000378:metabolism*; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D014867:Water
D000700:Analgesics; D014867:Water; D003907:Dexamethasone; D006854:Hydrocortisone