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

Abstract

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.

Figures

Fig. 1

Effects of sleep deficiency on neurobiological systems/mediators with predominantly analgesic or hyperalgesic properties. Systems/mediators with predominantly analgesic properties are presented in blue, those with analgesic and/or hyperalgesic properties (depending on site of action and receptors involved) are presented in purple, and those with predominantly hyperalgesic properties are presented in red. The effect of sleep deficiency on systems/mediators is indicated by up- and down- arrows, with up-arrows reflecting an activating influence and down-arrows reflecting a deactivating influence on systems/mediators. For example, activation of the opioid system has analgesic effects (blue), and sleep deficiency leads to reduced responsivity to exogenous opioids (down-arrow), suggesting that the pain-promoting effect of sleep deficiency is mediated by the opioid system. Not depicted are the many interactions between these systems and mediators, further emphasizing the complexity of the neurobiological mechanisms involved in the pain-promoting effects of sleep deficiency. LC: Locus coeruleus; CSF: cerebrospinal fluid; HPA: hypothalamus-pituitary adrenal; NO: nitric oxide, NOS: NO synthase; PAG: periaqueductal gray; IL: interleukin; TNF: tumor necrosis factor

Fig. 2

Clinical implications and research opportunities based on current knowledge of the sleep-pain relationship