Table 2

Associations* between biological stress systems function and onset of chronic multisite musculoskeletal pain

Onset of chronic pain
HR (95% CI)p ValueN†
HPA-axis
AUCga1339
 Sociodemographic adjusted‡1.08 (0.97 to 1.21)0.16
 Lifestyle and disease adjusted§1.10 (0.98 to 1.24)0.10
 Depression and anxiety adjusted¶1.08 (0.97 to 1.22)0.17
AUCia1339
 Sociodemographic adjusted‡0.99 (0.88 to 1.11)0.81
 Lifestyle and disease adjusted§1.00 (0.89 to 1.12)0.98
 Depression and anxiety adjusted¶0.99 (0.88 to 1.11)0.80
Mean evening levela1454
 Sociodemographic adjusted‡1.09 (0.97 to 1.22)0.14
 Lifestyle and disease adjusted§1.10 (0.97 to 1.24)0.14
 Depression and anxiety adjusted¶1.09 (0.96 to 1.23)0.19
Cortisol suppression ratioa1375
 Sociodemographic adjusted‡0.98 (0.87 to 1.09)0.67
 Lifestyle and disease adjusted§0.99 (0.88 to 1.11)0.79
 Depression and anxiety adjusted¶1.00 (0.89 to 1.12)0.94
IMS
CRPb2016
 Sociodemographic adjusted‡1.00 (0.91 to 1.11)0.97
 Lifestyle and disease adjusted§0.95 (0.85 to 1.05)0.30
 Depression and anxiety adjusted¶0.94 (0.85 to 1.05)0.29
IL-6b2016
 Sociodemographic adjusted‡1.08 (0.98 to 1.18)0.11
 Lifestyle and disease adjusted§1.04 (0.94 to 1.14)0.48
 Depression and anxiety adjusted¶1.04 (0.95 to 1.15)0.40
TNF-αb2002
 Sociodemographic adjusted‡1.00 (0.91 to 1.11)0.95
 Lifestyle and disease adjusted§0.98 (0.89 to 1.08)0.65
 Depression and anxiety adjusted¶0.98 (0.88 to 1.08)0.66
IMS
Basal summary indexb1994
 Sociodemographic adjusted‡1.04 (0.95 to 1.15)0.39
 Lifestyle and disease adjusted§0.99 (0.88 to 1.10)0.78
 Depression and anxiety adjusted¶0.99 (0.89 to 1.10)0.82
LPS summary indexb,c862
 Sociodemographic adjusted‡1.15 (0.95 to 1.39)0.17
 Lifestyle and disease adjusted§1.11 (0.91 to 1.34)0.32
 Depression and anxiety adjusted¶1.08 (0.89 to 1.32)0.42
ANS
Heart rated1951
 Sociodemographic adjusted‡1.03 (0.94 to 1.13)0.56
 Lifestyle and disease adjusted§1.02 (0.92 to 1.12)0.74
 Depression and anxiety adjusted¶1.01 (0.92 to 1.12)0.78
PEPd1937
 Sociodemographic adjusted‡0.93 (0.84 to 1.03)0.14
 Lifestyle and disease adjusted§0.93 (0.84 to 1.02)0.13
 Depression and anxiety adjusted¶0.94 (0.85 to 1.04)0.24
SDNNd1951
 Sociodemographic adjusted‡0.94 (0.85 to 1.04)0.22
 Lifestyle and disease adjusted§0.95 (0.86 to 1.05)0.34
 Depression and anxiety adjusted¶0.96 (0.87 to 1.06)0.44
RSAd,e1951
 Sociodemographic adjusted‡0.92 (0.83 to 1.03)0.14
 Lifestyle and disease adjusted§0.93 (0.84 to 1.04)0.19
 Depression and anxiety adjusted¶0.95 (0.85 to 1.06)0.35
  • *Using Cox regression analyses; HR=HR per 1 SD increase; ln-transformed variables were used for evening cortisol, postdexamethasone cortisol and basal inflammatory markers.

  • †Numbers of subjects do not total 2039 because of exclusion of subjects with missing or incomplete data.

  • ‡Adjusted for sex, age, years of education (and a cortisol sampling factors; c laboratory site; e respiration rate).

  • §Additionally adjusted for alcohol intake, smoking, body mass index, number of chronic diseases and physical activity (and b use of anti-inflammatory medication; duse of β blocking agents or other heart medication)

  • ¶Additionally adjusted for lifetime diagnoses of depressive and anxiety disorders and use of antidepressants.

  • ANS, autonomic nervous system; AUCg, area under the curve with respect to the ground; AUCi, area under the curve with respect to the increase; CRP, C reactive protein; HPA, hypothalamic-pituitary-adrenal; IMS, immune system; LPS, lipopolysaccharide; PEP, pre-ejection period; RSA, respiratory sinus arrhythmia; SDNN, SD of the normal-to-normal interval; TNF-α, tumour necrosis factor α.