Losing sleep over it: the link between chronic pain and sleep disturbances

19 May 2015  |  Print

Losing sleep over it: the link between chronic pain and sleep disturbances

Pain and sleep are both essential mechanisms for human survival. However, each can sometimes go awry, with potentially devastating consequences.

Chronic impairments in the systems that regulate pain and sleep can have many negative effects on health and well-being. In addition, both chronic pain and sleep disturbances share a variety of possible comorbidities, including obesity and type 2 diabetes.[1]

Furthermore, pain and sleeping problems appear to be closely intertwined: up to 88% of patients with chronic pain disorders suffer with sleep complaints, and at least 50% of those with insomnia – the most common sleep impairment disorder – also have chronic pain.[1,2] Ultimately, pain disturbs sleep continuity and quality, and poor sleep further exacerbates pain.[1] Mental problems associated with both, such as mood disturbances and depression, may provide an important link. Indeed, many chronic pain patients have underlying psychiatric conditions, despite only reporting physical symptoms.

This raises at least three key questions:

  • Are pain and sleep reciprocally related or does one precede the other?
  • What are the physiologic mechanisms that underlie their association?
  • What can be done to manage sleep problems in patients with chronic pain?

These questions are discussed below.

Relationship between pain and sleep

Early evidence suggested a reciprocal relationship between pain and sleep. A literature review performed 11 years ago found evidence, out of six studies involving patients with fibromyalgia, rheumatoid arthritis, burn injury and orofacial pain, for a pain→sleep directional effect in five studies, and for a sleep→pain directional effect in four studies.[1,2]

Since then, several further reports have provided data consistent with a bidirectional association between pain and sleep.[3,4]

For example, a study of 333 people hospitalized for major burns found that those reporting insomnia at discharge experienced significantly increased pain severity during long-term follow-up; meanwhile, greater pain severity during the week preceding discharge predicted increased rates of long-term sleep disturbances.[3]

However, across a number of studies, a trend has now emerged suggesting that sleep disturbance may be a stronger predictor of pain than vice versa.[1] Indeed, in a study that modelled the associations between sleep, pain, depression and fatigue in a group of over 11,000 cancer patients, the best fitting model included a path in which sleeping problems predicted pain. Inclusion of the reverse path, in which pain predicted sleeping problems, produced a poorer fitting model.[4]

This does not necessarily diminish the value of chronic pain as a risk factor for sleep disturbance. However, the potential implication is very important: by treating the sleep disorder, we may be able to improve the chronic pain.

Underlying mechanisms

Given that it is now established that sleep and pain are associated, future work should focus more on how they are linked. Three broad areas hold the greatest promise:[1]

  • Dopaminergic signaling – Dopamine is closely involved in the regulation of sleep and waking states. Dopamine receptors are abundant in the raphe nuclei of the brainstem, involved in sleep modulation; the signaling of the raphe cells may become dysregulated in the course of chronic pain.
  • Opioidergic signaling – Opioid peptides play a key role in pain modulation, and sleep deprivation may dysregulate opioid systems.
  • Mood and emotion – Elevations in ‘negative affect’, in particular mood and emotion, may explain some of the link between sleep disturbance and pain in non-clinically depressed patients. However, further work is required to understand the temporal dynamics of the association between sleep, pain and negative mood. The release of pro-inflammatory cytokines has been associated with the pathophysiology of pain, sleep disturbance and depression, and could play a role in linking them together.[5]

Managing sleep problems in chronic pain patients

The first step to effective management is proper evaluation. Precipitating factors should be identified, and an adequate sleep history obtained, including sleep and wakefulness patterns, family background of sleep disorders, and prior treatments.[6] Patients should also be screened for underlying depression and anxiety.

Management can involve both non-pharmacologic and pharmacologic approaches. In the former group, sleep hygiene and behavioral interventions are key.

Sleep hygiene measures are often simple for patients to introduce, and may include: winding down during the last 60-90 minutes before bedtime; use of relaxation techniques; maintenance of a healthy physical condition; avoidance of large meals and coffee/tea/alcohol; smoking cessation; using the bed only for sleep (and sexual activity); and regular sleeping hours.[6] Minimization of light stimuli for at least 2 hours before bedtime and avoidance of clock watching may also be valuable.

Numerous behavioral interventions can also be used, and can often be applied without referral to a specialist. For example, ‘stimulus control’ provides simple instructions aimed at curtailing behaviors that are incompatible with sleep. Meanwhile, ‘imagery training’ involves patients focusing on pleasant or neutral images. Other interventions, typically provided by specialists, include biofeedback and cognitive behavioral therapy.[6]

Various pharmacologic approaches can be used to supplement these techniques. For example, sedating antidepressants and atypical antipsychotic medications are frequently used. Benzodiazepines can produce significant short-term gains – including reduced time to sleep onset and fewer nighttime awakenings – but they are associated with side effects, like morning sedation and dependence.[7]

Newer drug classes include the benzodiazepine receptor agonists (BZRAs). These have comparable efficacy to benzodiazepines, but with a more limited side-effect profile.[7] However, a meta-analysis found that although the BZRAs are safer, they still pose a risk of harm.[8] A further option is ramelteon, a melatonin receptor agonist that has effects on endogenous circadian rhythms. It is generally well-tolerated and can have a positive impact on sleep onset.[7]

Overall, the management of sleep disturbances in patients with chronic pain remains challenging. Careful evaluation, good diagnostic skills and effective use of non-pharmacologic approaches are at least as important as the deployment of drug therapies.[6]


  1. 1. Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. J Pain 2013;14:1539-1552.
  2. 2. Smith MT, Haythornthwaite JA. How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature. Sleep Med Rev 2004;8:119-132.
  3. 3. Smith MT, Klick B, Kozachik S, et al. Sleep onset insomnia symptoms during hospitalization for major burn injury predict chronic pain. Pain 2008;138:497-506.
  4. 4. Stepanski EJ, Walker MS, Schwartzberg LS, et al. The relation of trouble sleeping, depressed mood, pain, and fatigue in patients with cancer. J Clin Sleep Med 2009;5:132-136.
  5. 5. Doong SH, Dhruva A, Dunn LB, et al. Associations between cytokine genes and a symptom cluster of pain, fatigue, sleep disturbance, and depression in patients prior to breast cancer surgery. Biol Res Nurs 2014. [Epub ahead of print].
  6. 6. Stiefel F, Stagno D. Management of insomnia in patients with chronic pain conditions. CNS Drugs 2004;18:285-296.
  7. 7. Pigeon WR, Bishop TM, Marcus JA. Advances in the management of insomnia. F1000 Prime Rep 2014;6:48.
  8. 8. Buscemi N, Vandermeer B, Friesen C, et al. The efficacy and safety of drug treatments for chronic insomnia in adults: a meta-analysis of RCTs. J Gen Intern Med 2007;22:1335-1350.