Hair-Normalized Cortisol Waking Response as a Novel Biomarker of Hypothalamic-Pituitary-Adrenal Axis Activity following Acute Trauma: A Proof-of-Concept Study with Pilot Results
The mechanisms underlying the development of persistent posttraumatic pain and disability remain elusive. Recent evidence suggests that disordered stress-system pathway (hypothalamic-pituitary-adrenal axis) activity may be responsible for the genesis and maintenance of long-term sensory and emotional problems. However, confidence in current evidence is limited by the necessarily retrospective collection of data. Hair cortisol can serve as a calendar of HPA axis activity going back several months prior to injury. The purposes of this pilot study were to determine the feasibility of using hair cortisol and hair-normalized salivary cortisol as biomarkers of distress following traumatic injuries of whiplash or distal radius fracture. Ten subjects provided complete data within 3 weeks of injury. Hair cortisol, cortisol waking response (CWR), and mean daily cortisol (MDC) were captured at inception, as were self-report indicators of pain, disability, and pain catastrophizing. Pain and disability were also captured 3 months after injury. Results indicate that cortisol waking response may be a useful biomarker of current distress as measured using the pain catastrophizing scale, especially when normalized to 3-month hair cortisol ( raw, 0.93 normalized). Hair-normalized CWR may also have predictive capacity, correlating with 3-month self-reported disability at . While promising, the results must be viewed in light of the small sample. 1. Introduction Chronic pain and disability are responsible for staggering socioeconomic burden [1–3], estimated to affect between 1 in 3 and 1 in 5 adults in developed countries [4, 5]. Effective treatment for noncancer chronic pain and disability remains elusive, usually relying on multimodal care often including complex and potentially risky pharmaceutical regimens. Logically, predicting and preventing the development of chronic problems could solve many of these current challenges. However, the mechanisms underlying the transition from acute to chronic pain and disability following musculoskeletal trauma remain poorly understood. A number of theoretical models or frameworks have been proposed in an attempt to demystify the development of chronic pain. These range from purely structural/anatomical [6] to purely cognitive [7] and to integrated biological and psychological [8]. A consistent thread across many of the existing frameworks and empirical studies addressing prognosis or features of chronic pain is the presence of physiological or emotional distress. Distress is a key component of many cognitive models, often framed in
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