Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications

Neuropsychopharmacology. 2020 Jan;45(1):205-216. doi: 10.1038/s41386-019-0439-z. Epub 2019 Jun 17.


Pain can be both a cause and a consequence of sleep deficiency. This bidirectional relationship between sleep and pain has important implications for clinical management of patients, but also for chronic pain prevention and public health more broadly. The review that follows will provide an overview of the neurobiological evidence of mechanisms thought to be involved in the modulation of pain by sleep deficiency, including the opioid, monoaminergic, orexinergic, immune, melatonin, and endocannabinoid systems; the hypothalamus-pituitary-adrenal axis; and adenosine and nitric oxide signaling. In addition, it will provide a broad overview of pharmacological and non-pharmacological approaches for the management of chronic pain comorbid with sleep disturbances and for the management of postoperative pain, as well as discuss the effects of sleep-disturbing medications on pain amplification.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Animals
  • Chronic Pain / physiopathology*
  • Chronic Pain / psychology
  • Chronic Pain / therapy
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology
  • Melatonin / physiology
  • Melatonin / therapeutic use
  • Pain Management / methods*
  • Pituitary-Adrenal System / physiopathology
  • Sleep / physiology*
  • Sleep Wake Disorders / physiopathology*
  • Sleep Wake Disorders / psychology
  • Sleep Wake Disorders / therapy


  • Analgesics, Opioid
  • Melatonin