Bidirectional Relationship Between Insomnia and Localized Pain Revealed

A bidirectional relationship exists between insomnia and localized pain in the head, neck/shoulder, back, and hip regions.

A causal relationship exists between localized pain and common mental disorders, such as insomnia, according to study findings published in The Journal of Headache and Pain.

For the study, researchers utilized genetic data and Mendelian randomization (MR) to investigate the potential relationship between pain in different regions and the likelihood of common mental disorders.

The researchers selected instrumental from 8 localized pain genome-wide association studies (GWAS) and 3 mental disorder GWAS. Seven localized pain sites (headache, facial pain, neck/shoulder pain, back pain, stomach/abdominal pain, hip pain, and knee pain) and 3 mental disorders (sleeplessness/insomnia, anxiety/panic attacks, and depression) were chosen as exposure factors and outcome indicators, respectively, and a bidirectional framework was applied.

An inverse-variance weighted (IVW) MR method was used to assess the relationship between localized pain and mental disorders, with a multiplicative random effect IVW model used in the case of heterogeneity and a fixed-effect IVW model used otherwise. The MR-Egger regression was used for pleiotropic effects and the F statistic was used to assess potential weak instrument bias.

The outcome demonstrated a robust and significant bidirectional association between the genetic susceptibility of pain and insomnia, as well as between pain and depression.

The researchers found that multiple localized pain sites are significant predisposing factors for certain mental disorders.

Significant predisposing factors sleeplessness/insomnia included:

  • headache (odd ratios [OR], 1.14; 95% CI, 1.05–1.24; P =.04),
  • neck/shoulder pain (OR, 1.95; 95% CI, 1.03–3.68; P =.03),
  • back pain (OR, 1.40; 95% CI, 1.22–1.60; P <.001), and
  • hip pain (OR, 2.29; 95% CI, 1.18–4.45, P <.001).

Significant predisposing factors for depression included:

  • headache (OR, 1.06; 95% CI, 1.03–1.08; P <.001),
  • neck/shoulder pain (OR, 1.09; 95% CI, 1.01–1.17, P =.02),
  • back pain (OR, 1.08; 95% CI, 1.03–1.14; P =.02),
  • stomach/abdominal pain (OR, 1.19; 95% CI, 1.11–1.26; P <.001), and
  • knee pain (OR, 1.07; 95% CI, 1.02–1.13; P = .004).

The absence of pain was associated with significantly lower genetic susceptibility for:

  • sleeplessness/insomnia (OR, 0.62; 95% CI, 0.54–0.70; P <.001),
  • anxiety/panic attacks (OR, 0.98; 95% CI, 0.97–1.00; P =.01), and
  • depression (OR, 0.92; 95% CI, 0.90–0.95; P <.001).

Reverse directional MR found that certain mental disorders are significant predisposing factors for multiple localized pain sites:

  • headache (OR, 1.09; 95% CI, 1.06–1.12; P <.001),
  • facial pain (OR, 1.01; 95% CI, 1.00–1.02; P =.02),
  • neck/shoulder pain (OR, 1.12; 95% CI, 1.07–1.16; P <.001),
  • back pain (OR, 1.12; 95% CI, 1.07–1.18; P <.001),
  • stomach/abdominal pain (OR, 1.06; 95% CI, 1.04–1.08; P <.001),
  • hip pain (OR, 1.08; 95% CI, 1.05–1.10; P <.001), and
  • knee pain (OR, 1.09; 95% CI, 1.04–1.13; P <.001).

Sleeplessness/insomnia is a significant predisposing factor for pain at all sites.

Anxiety/panic attacks was a significant predisposing factor for neck/shoulder pain (OR, 1.83; 95% CI, 1.28–2.62; P <.001) and back pain (OR, 1.54; 95% CI, 1.06–2.23; P =.02).

Depression was a significant predisposing factor for:

  • headache (OR, 1.28; 95% CI, 1.08–1.52, P =.004),
  • facial pain (OR, 1.07; 95% CI, 1.02–1.12; P =.006),
  • neck or shoulder pain (OR, 1.32; 95% CI, 1.16–1.50; P <.001),
  • back pain (OR, 1.35; 95% CI, 1.10–1.66; P =.004),
  • stomach and abdominal pain (OR, 1.14; 95% CI, 1.05–1.25; P =.002), and
  • hip pain (OR, 1.17; 95% CI, 1.04–1.31; P =.01).

Study limitations included the use of GWAS with self-reported data captured via questionnaires. Also, participants may have had multiple sites of pain occurring at the same time such that the effects of each localized pain site in the statistical analysis were not independent. Additionally, participants may have been taking medication(s) that could have covered up potential psychological disorders or pain.

The researchers concluded, “The outcome demonstrated a robust and significant bidirectional association between the genetic susceptibility of pain and insomnia, as well as between pain and depression.”

Addressing pain from both physical and psychological angles may improve symptom management and patient quality of life.

This article originally appeared on Clinical Pain Advisor


Yao C, Zhang Y, Lu P, et al. Exploring the bidirectional relationship between pain and mental disorders: a comprehensive Mendelian randomization study. J Headache Pain. Published online July 7, 2023. doi:10.1186/s10194-023-01612-2