Why sleep matters in chronic pain: evidence across the lifespan

Summary

Sleep problems commonly coexist with chronic pain conditions, with growing evidence that they may precede and contribute to pain persistence. Meanwhile, pain itself can disturb sleep, creating a bidirectional relationship. In this narrative review we explore how the sleep–pain relationship changes across the lifespan. In childhood and adolescence, poor sleep may predict the emergence of pain, possibly through neurodevelopmental impacts on pain modulation and affective regulation. In adulthood, sleep interacts with lifestyle, psychological state and occupational stressors to shape pain risk. In older adults, chronic pain and comorbidities such as sleep apnoea and depression may further impair sleep quality, reinforcing a vicious cycle. Across all stages, shared mechanisms, such as hypothalamic-pituitary-adrenal axis dysregulation, neuroinflammation, and impaired glymphatic clearance may contribute to this interplay. Recognising early sleep disturbance as a modifiable risk factor for later pain offers opportunities for prevention, while improving sleep may reduce the impact of established chronic pain.

Introduction

Chronic pain is a major contributor to disability and reduced quality of life, affecting up to half of the adult population and imposing significant personal and societal costs.¹ Sleep disturbance affects approximately three-quarters of adults with chronic pain,² and is prioritised by both patients and clinicians for research and treatment.³

Pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage”, with chronic pain defined as pain persisting for 3 or more months.¹ Pain can arise through peripheral, nociceptive mechanisms (reflecting tissue injury or inflammation), neuropathic mechanisms (resulting from lesion or disease of the somatosensory system), or central nervous system, nociplastic mechanisms (arising from altered nociception despite no clear evidence of tissue or neural damage).¹ In the most recent International Classification of Diseases (ICD-11), chronic primary pain refers to pain that constitutes a disease in its own right and cannot be better explained by another condition; while chronic secondary pain occurs as a symptom of an identifiable underlying disease process (e.g. nerve injury, osteoarthritis).⁴

Sleep is a physiologically regulated state comprising distinct stages, including non-rapid eye movement (NREM) sleep, of which slow-wave sleep (SWS) represents the deepest, most restorative phase, and rapid eye movement (REM) sleep, characterised by dreaming and heightened cortical activity. Throughout this review, the term sleep quality refers to subjective and objective indices of sleep continuity, duration, and architecture.

Despite recent advances, the neurobiological mechanisms linking sleep and pain remain unclear, particularly how they evolve across different stages of life. While the relationship between sleep and chronic pain has traditionally been seen as bidirectional,⁵ observational and experimental studies indicate that sleep disturbance may be a stronger predictor of future pain than vice versa.6, 7, 8 Targeting sleep offers a promising therapeutic avenue for preventing the onset of, and alleviating, chronic pain. For example, cognitive behavioural therapy for insomnia (CBT-I) improves sleep quality in chronic pain conditions,⁹ such as fibromyalgia,¹⁰ with some evidence for downstream benefits on pain. However, there is comparatively little study of the effect of pain itself on sleep architecture and quality–a notable gap in the literature and a promising avenue for future exploration.

In this narrative review, we examine the sleep–pain relationship through a lifespan lens, integrating findings from neurobiological, epidemiological, and clinical research. We explore how sleep disturbances shape pain vulnerability across the lifespan and highlight opportunities for prevention and intervention.

Search strategy and selection criteria

We conducted a narrative, integrative review. This was not a systematic review and did not follow PRISMA methodology; instead, it reflects a targeted synthesis of selected influential work aimed at integrating concepts across developmental stages. Data for this review were identified through searches of MEDLINE (Ovid), PubMed, and references from relevant articles, using the search terms “sleep”, “insomnia”, “sleep disturbance”, “pain”, “chronic pain”, “nociplastic”, “fibromyalgia”, “children”, “adolescents”, “teenagers”, “adults”, and “older adults.” Only articles published in English prior to June 2025 were considered. A glossary of key terms is given in Table 1.

Table 1.

Glossary of key terms.

Chronic pain	Pain lasting >3 months, persisting beyond normal tissue healing, and often associated with functional and psychological impacts.
Pain mechanisms
Nociceptive pain	Pain arising from actual or potential tissue damage (e.g. acute injuries such as burns or surgical wounds), mediated by activation of nociceptors.
Neuropathic pain	Pain caused by a lesion or disease of the somatosensory nervous system (e.g. diabetic neuropathy, post-herpetic neuralgia).
Nociplastic pain	Pain from altered nociception without clear evidence of tissue or nerve damage (e.g. fibromyalgia); associated with central sensitisation.
Central sensitisation	Heightened responsiveness of the central nervous system to sensory input, amplifying pain signals and contributing to hyperalgesia and allodynia.
Sleep architecture	The cyclical pattern of NREM and REM sleep stages that support physical and cognitive restoration.
NREM/REM sleep
NREM	Non-REM sleep includes stages 1–3; Stage 3 (slow-wave sleep, SWS) is especially restorative.
REM	Characterised by rapid eye movements, vivid dreaming, and muscle atonia.
Hyperarousal	Hyperarousal: A state of increased CNS activation linked to insomnia and pain, involving elevated stress reactivity, autonomic arousal, and cortical alertness.
CBT-I (Cognitive Behavioural Therapy for Insomnia)	A structured, multicomponent treatment targeting thoughts and behaviours that maintain insomnia; first-line therapy for insomnia, with demonstrated benefit in pain populations.

Conceptual and neurobiological framework

Clinical picture: sleep disturbances in chronic pain

Sleep disturbance is a prominent feature of many chronic pain conditions and may involve insomnia symptoms (i.e. difficulty initiating sleep, early morning waking, or non-refreshing sleep), circadian misalignment, or fragmentation of sleep architecture, particularly SWS. Understanding these clinical patterns is important for interpreting the mechanistic models presented in Section 2.2 and the lifespan trajectories discussed in Section 3. These disturbances may not only be a troubling comorbidity of pain but may also contribute to pain persistence (Table 2).

Table 2.

Sleep disturbance across pain conditions: Common features, assessment approaches, and mechanistic insights.

Condition	Common sleep issues	Sleep measurement (Subjective versus Objective)	Mechanistic insights
Fibromyalgia(Moldofsky 1989, Choy 2015, Wu, Chang et al. 2017)	Insomnia (difficulty falling and staying asleep), non-restorative “light” sleep (frequent awakenings, alpha-delta intrusion in NREM sleep), comorbidities (e.g. RLS)	Both subjective reports (poor sleep quality, fatigue upon waking) and objective findings (PSG shows reduced sleep efficiency, both short or long total sleep, less slow-wave sleep)	Altered sleep architecture (intrusion of alpha waves into deep sleep), hyperarousal (heightened CNS and HPA-axis activity) maintaining a cycle of light, unrefreshing sleep
Osteoarthritis (OA) (Parmelee, Tighe et al. 2015, Taylor, Oddone et al. 2018)	Insomnia due to pain (difficulty initiating and maintaining sleep), frequent pain-related awakenings, early morning waking; often sleep fragmentation, comorbidities (e.g. OSA)	Primarily subjective, with limited objective data (actigraphy/PSG show pain-related arousals; comorbid OSA in some patients)	No unique sleep-stage abnormality identified beyond pain-driven disruption; chronic joint pain causes micro-arousals and poor sleep continuity, and inflammation or comorbid obesity can contribute to sleep-disordered breathing (OSA), creating a vicious pain–sleep cycle
Neuropathic Pain (e.g. peripheral neuropathy, trigeminal neuralgia) (Almoznino, Haviv et al., 2017, Ferini-Strambi 2017)	Marked insomnia and fragmented sleep (burning or electric pain provokes awakenings); reduced sleep efficiency and shortened REM and deep sleep observed in some neuropathies	Surveys show majority have poor sleep; objective PSG in specific neuropathic conditions reveals fragmented sleep with decreased REM and NREM stage 3–4, and frequent awakenings from pain	Peripheral nerve pain signals disrupt normal sleep maintenance. Bidirectional feedback exists: pain-induced sleep loss heightens pain sensitivity and central sensitization, further exacerbating neuropathic pain. Night-time hypervigilance to pain stimuli leads to persistent arousal and loss of restorative sleep
Endometriosis(Zhang, Liu et al. 2024)	High prevalence of insomnia and poor sleep quality (≈70% of patients). Pelvic pain (especially during menses) causes difficulty sleeping, frequent night-time awakenings, and unrefreshing sleep; often accompanied by daytime fatigue	Largely subjective measures (e.g. PSQI scores often high; many report moderate-to-severe insomnia). Few studies with PSG, but patient reports consistently indicate significantly disrupted sleep during pain flares	Chronic pelvic pain and dysmenorrhea lead to nocturnal arousals and shortened sleep duration (pain can increase sleep disturbances ∼5–6-fold). Hormonal influences and elevated anxiety/depression in endometriosis contribute to hyperarousal, which mediates insomnia and fragmented sleep architecture
Chronic Headache (Migraine) (Tiseo, Vacca et al. 2020)	Insomnia and poor sleep quality are common (migraine sufferers often report trouble initiating sleep and non-restorative sleep, especially around headache episodes). Co-occurring sleep disorders (e.g. higher risk of sleep apnoea) are more frequent than in non-migraineurs	Predominantly subjective assessment (questionnaires show migraineurs have worse sleep quality and more frequent insomnia complaints than controls). Some objective studies suggest subtle changes (e.g. altered REM latency or efficiency), but findings are inconsistent; migraine attacks themselves can disrupt normal sleep patterns	Shared neurobiological pathways link sleep regulation and migraine: hypothalamic and brainstem centres (and neurotransmitters like serotonin, dopamine, orexin) involved in sleep-wake cycles also drive migraine pathophysiology. Sleep disruption can trigger migraines and, conversely, sleep can relieve attacks—highlighting a bidirectional relationship underpinned by common mechanisms (e.g. dysregulated circadian and pain modulatory systems)
Irritable Bowel Syndrome (IBS) (Tu, Heitkemper et al. 2017)	Insomnia symptoms (difficulty falling asleep, frequent night awakenings) and non-restorative sleep are frequently reported. Patients often sleep longer yet feel less rested (unrefreshing sleep), with many experiencing light, fragmented sleep overnight	Mostly subjective evaluations: a significant proportion (∼38% in meta-analysis) have clinical sleep disturbances by self-report, and poorer self-reported sleep correlates with worse next-day GI symptom severity. Objective measures (PSG, actigraphy) have not consistently shown major abnormalities, suggesting some sleep state misperception (perceived sleep worse than measured)	Visceral pain and discomfort lead to arousals and sleep fragmentation via gut–brain signalling. Stress and anxiety (common in IBS) promote a state of physiological hyperarousal that interferes with sleep continuity. In turn, poor sleep can lower pain thresholds and exacerbate visceral hypersensitivity, creating a reciprocal pain–sleep aggravation cycle
Chronic Low Back Pain(Kelly, Blake et al. 2011)	Chronic back pain sufferers typically have insomnia (delayed sleep onset and frequent awakenings due to pain). Shortened total sleep time, low sleep efficiency, and non-restorative sleep are prevalent (over three-quarters report persistent sleep disturbances)	Assessed mainly by patient-reported outcomes: high rates of poor sleep quality and clinical insomnia in chronic low back pain. Objective studies (case–control PSG or actigraphy) confirm reduced sleep efficiency and greater sleep fragmentation compared to pain-free individuals (e.g. more movement and wakefulness during the night)	Pain-induced micro-arousals disrupt normal sleep stages, preventing deep restorative sleep. A robust bidirectional link exists: chronic pain disturbs sleep, while sleep deprivation heightens pain perception and muscular tension. No specific EEG signature is unique to back pain, but the chronic pain state sustains a cycle of somatic hypervigilance at night and increased next-day pain via central sensitization

This table summarises key sleep-related disturbances in a range of chronic pain conditions, detailing their typical clinical presentation, the nature of sleep assessment (subjective versus objective), and proposed mechanistic underpinnings. Abbreviations: PSG, polysomnography; PSQI, Pittsburgh Sleep Quality Index; REM, rapid eye movement; NREM, non-rapid eye movement; SWS, slow-wave sleep; OSA, obstructive sleep apnoea; RLS, restless legs syndrome; CNS, central nervous system; HPA, hypothalamic-pituitary-adrenal.^5,11, 12, 13, 14, 15, 16, 17, 18, 19, 20

Sleep duration and insomnia phenotypes

Insights from insomnia subtypes are relevant to pain populations. Insomnia with objective short sleep duration (ISS) has received particular attention in sleep research. It is associated with cognitive dysfunction and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, including elevated nocturnal cortisol, and appears less responsive to sleep treatments such as CBT-I.²¹ In adults with temporomandibular joint (TMJ) disorder, ISS is associated with more severe pain, greater functional limitations, and elevated levels of interleukin (IL)-6, an inflammatory marker, compared with insomnia with normal sleep duration.²² Similarly, patients with fibromyalgia display features that overlap with ISS. A systematic review and meta-analysis of 47 observational studies (n = 1465 fibromyalgia, n = 1192 controls) found evidence suggestive of adrenocortical hypofunction and elevated sympathetic tone in fibromyalgia.²³ However, substantial heterogeneity, contradictory findings, and publication bias limit these conclusions.

In patients with chronic pain, self-reported sleep duration exhibits a U-shaped relationship with clinical outcomes. Short sleep has been linked to attentional deficits,²⁴ while prolonged sleep may reflect non-restorative processes due to pain-related arousals or comorbid sleep disorders such as obstructive sleep apnoea (OSA).²⁵ However, subjective misestimation complicates assessment. In an observational study of 159 predominantly male veterans, those with insomnia under-reported actual sleep duration compared to their actigraphy measures, whereas fragmented sleepers overestimated duration.²⁶

Fibromyalgia as a clinical model

Fibromyalgia's well-characterised phenotype makes it a valuable model for understanding how disrupted sleep contributes to pain.²⁷ Up to 90% report persistent sleep problems, particularly non-restorative sleep.⁵ Impaired sleep is also particularly implicated in the future development of widespread pain, the characteristic feature of fibromyalgia and other nociplastic pain disorders.⁸ Sleep disturbances are linked not only to pain but also to cognitive dysfunction and mood symptoms characteristic of nociplastic pain.⁵ While fibromyalgia illustrates key features of sleep-pain interactions, patterns vary across pain conditions (Table 2). For instance, in osteoarthritis, sleep disturbance is characterised primarily by frequent awakenings and reduced sleep efficiency rather than the marked alterations in sleep architecture seen in fibromyalgia, with pain severity appearing to drive sleep disruption more directly.^11,12 This heterogeneity suggests the sleep–pain relationship may vary across causes of pain; this is explored further in section 2.2.

Having established the clinical patterns of sleep disturbance in chronic pain, we now turn to hypothesised mechanistic models that may explain these relationships.

Hypothesised Models of sleep–pain interactions

We propose three conceptual models for the sleep–pain relationship: 1) sleep disturbance increases pain vulnerability, 2) pain disrupts sleep, and 3) both are driven by shared neurobiological mechanisms (Fig. 1).

Fig. 1.

Hypothesised models of sleep-pain interactions. This conceptual model illustrates the bidirectional relationship between sleep disruption and pain, highlighting how each can drive and perpetuate the other through multiple interacting mechanisms. In the first pathway, sleep disruption increases vulnerability to pain by altering sleep architecture and reducing sleep duration, leading to hyperarousal, impaired recovery from tissue damage, and dysregulation of neuroimmune and neuroendocrine systems. These changes heighten pain sensitivity and inflammation, mediated through both neurobiological and behavioural or psychosocial processes such as inactivity or obesity. In the second pathway, pain disrupts sleep by causing nocturnal awakenings and interfering with restorative sleep stages. This effect is mediated by biological mechanisms such as peripheral inflammation and by behavioural or psychological factors including anxiety, depression, circadian disruption, and medication use. A third shared pathway reflects common neurobiological antecedents that contribute to both sleep disturbance and pain. These include dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, altered limbic and brainstem regulation, immune dysregulation, and impaired glymphatic clearance. These shared factors may predispose individuals to both conditions and help explain their frequent co-occurrence. Together, these pathways underscore the complex, multidimensional relationship between sleep and pain and point to the importance of integrated approaches to research and clinical care.

Sleep disturbance increases pain vulnerability

Clinical and experimental studies suggest poor sleep heightens pain sensitivity. Experimental sleep restriction in healthy adults impairs descending pain inhibition and enhances pain facilitation.²⁸ Moldofsky's early work demonstrated that selectively disrupting deep sleep in a small sample of healthy individuals induced widespread pain, fatigue, and mood changes resembling fibromyalgia, which resolved with recovery sleep.29, 30, 31 The ‘alpha-delta’ EEG pattern observed in these studies, characterised by intrusion of relatively high frequency alpha waves into deep sleep, is also associated with increased next-day pain and non-restorative sleep in a group of healthy middle-age women,^32,33 and may serve as a marker of sleep-related CNS dysfunction. Together, these experiments support the hypothesis that nociplastic-like symptoms can arise from disrupted restorative sleep, though whether naturally occurring sleep disturbances in clinical populations produce similar effects requires further investigation.

Longitudinal studies further support this temporal relationship in large population-based cohorts, including UK Biobank.⁸ In patients undergoing joint replacement surgery, sleep disturbance is one of a number of factors associated with a greater risk of persistent post-operative pain.^34,35 However, evidence that treating sleep impairment alleviates pain (which would support a causal role) is less consistent.³⁶

Pain disrupts sleep

Pain may also affect sleep through a combination of direct nociceptive input, hyperarousal, and cognitive-emotional activation. However, in contrast to the larger body of literature exploring the effect of sleep on pain, there is a relative paucity of evidence for the effect of pain itself on sleep, restricted largely to pre-clinical studies and relatively small studies of healthy volunteers.

In animals, experimentally induced arthritis provides a disease model of chronic inflammatory pain. In an early rat model of arthritis, there was an absence of diurnal variation in sleep-wake cycles and increased sleep fragmentation.³⁷ Similar findings were observed in a more recent mouse study, where inflammatory pain disrupted diurnal variation in sleep.³⁸ Inflammatory pain increases sleep during normally active periods, while decreasing and fragmenting sleep during normally quiescent periods. This may represent an adaptive response to increasing safety in the context of injury-associated vulnerability to predatory threats.^39,40 In models of neuropathic pain, rats with spinal nerve lesions exhibited a 20% reduction in NREM sleep, increased wakefulness, and pronounced sleep fragmentation with frequent brief awakenings.⁴¹ These findings suggest that pain reduces SWS and alters sleep-wake architecture, though the specific patterns may differ by pain mechanism.

Meanwhile, small experimental studies in healthy human volunteers provide evidence that acute pain disrupts sleep microstructure. In a study of 10 healthy male volunteers, experimentally-induced muscle and joint pain stimuli during SWS altered sleep EEG patterns, with reduced delta wave and increased beta activity suggestive of cortical arousal.⁴² However, cutaneous pain produced no EEG changes suggesting effects may be specific to pain modality. In a cross-over study of 13 healthy young adults, experimentally-evoked muscle pain (intramuscular hypertonic saline) disrupted both light and deep NREM sleep, with reduced subjective sleep quality the following morning.⁴³ However, in another small study of nine healthy adults, delayed-onset muscle pain induced by eccentric exercise did not impact sleep.⁴⁴ Furthermore, experimental pain stimuli must be time-limited to prevent tissue damage, restricting how well these findings translate to the sustained pain experienced in chronic pain.

Observational studies in chronic pain show variable patterns. In an ecological study of 160 older adults with osteoarthritis, poor sleep predicted next-day pain but pain did not impact subsequent sleep,⁴⁵ whereas in a longitudinal study of 1660 middle-aged adults with physical disabilities, bidirectional effects were observed.⁴⁶ This heterogeneity likely reflects methodological differences (subjective versus objective sleep assessment, pain measurement approaches, cohort characteristics) as well as genuine variation in how pain chronicity and age moderate the sleep–pain relationship.

Shared neurobiological antecedents

Pain and sleep disturbance may share common neurobiological antecedents, though much of the evidence is also derived from animal models. Proposed shared mechanisms include dysfunction of the descending pain modulatory system (DPMS), HPA axis, and limbic circuits.

In rodents, acute sleep loss reduces GABAergic inhibition in the periaqueductal grey (PAG), impairing pain inhibition,⁴⁷ while chronic sleep loss increases PAG excitability and pain sensitivity.⁴⁸ PAG GABAergic neurons also regulate REM-NREM transitions, suggesting a mechanistic link.⁴⁹ The amygdala may play a shared role through its involvement in emotional regulation. Brain imaging in patients with primary insomnia demonstrates altered amygdala connectivity with limbic and subcortical regions,⁵⁰ while in healthy adults, shorter self-reported sleep is associated with reduced amygdala-ventromedial prefrontal cortex (vmPFC) coupling and emotional dysregulation.⁵¹ However, both studies excluded participants with psychopathology, a common comorbidity in chronic pain, limiting generalisability.

Sleep also modulates immune signalling. Experimental sleep deprivation elevates pro-inflammatory cytokines and activates NF-κB and STAT pathways (see a review by Irwin⁵² summarising human and animal studies) promoting pain sensitisation.⁵³ Neuroinflammation is also a feature of fibromyalgia and other nociplastic conditions, and is associated with sleep problems in human neuroimaging studies.⁵⁴ These effects may differ by pain phenotype: neuropathic pain involves inflammation at multiple levels of the neuraxis,⁵⁵ while nociplastic pain shows central glial activation, potentially triggered by peripheral immune factors.⁵⁶

The glymphatic system, which clears metabolic waste during SWS, may play a role. A systematic review of 199 studies (n = 19,129 individuals) implicates the glymphatic system in neurodegeneration and cognitive impairment.⁵⁷ Human PET studies demonstrate that amyloid-β (Aβ) accumulates in the healthy brain after a single night of sleep deprivation.⁵⁸ Conversely, individuals with early Aβ deposition report increased wakefulness and altered sleep patterns, as do those with mild dementia due to Alzheimer's Disease, suggesting a bidirectional relationship between sleep and neurodegenerative disease.⁵⁹ However, whether glymphatic dysfunction contributes to pain chronification in humans, and how sleep behaviour modifies glymphatic function, remain an area of active investigation.^60,61

Neuroimaging studies have linked both short and long sleep durations to alterations in grey and white matter, with downstream effects on executive function, though such findings remain underexplored in chronic pain populations.⁶² Functional neuroimaging during attention tasks suggest that poor sleepers exhibit lapses in sustained attention, marked by increased default mode network and reduced dorsal attention network activity.⁶³ Overall, preclinical and neuroimaging evidence points to potential shared mechanisms, though the extent to which these pathways mediate sleep-pain interactions in clinical populations remains to be established.

Phenotype-specific manifestations

Sleep-pain interactions may manifest differently across pain phenotypes. In nociplastic pain, fragmented sleep may exacerbate central sensitisation, reduced glymphatic clearance, and neuroimmune activation. Meanwhile, in nociceptive pain the relationship between inflammation and recovery may be more complex. A longitudinal study of 83 patients with acute low back pain identified distinct inflammatory profiles associated with different recovery trajectories.⁶⁴ One subgroup characterised by elevated acute-phase CRP and IL-6 (alongside poor sleep quality) showed the best recovery over 12 months, with inflammatory markers decreasing progressively. In contrast, a subgroup with persistently elevated tumour necrosis factor (TNF) and depression showed the poorest recovery. Acute CRP and IL-6 elevations may support recovery, while persistent overexpression of TNF may perpetuate pain. The directionality of the sleep–inflammation relationship remains unclear, though sleep disruption could plausibly modulate inflammatory resolution during acute pain. Whether sleep influences these inflammatory trajectories remains unclear. Nevertheless, given the role of sleep in immune regulation, disrupted sleep during acute pain may influence the resolution or persistence of nociceptive pain.

The relative importance of these mechanisms may shift across the lifespan, though direct evidence remains limited, as will be discussed in the following section. In infancy and childhood, immature descending pain modulation and circadian consolidation may dominate, with sleep disruption potentially interfering with prefrontal-limbic maturation. In adulthood, psychosocial stressors appear to interact with inflammatory and HPA-axis pathways, while lifestyle factors (e.g. obesity, shift work) amplify these effects. In older age, declining glymphatic function, chronic low-grade inflammation, and comorbidities appear to converge with sleep architecture changes, reinforcing bidirectional feedback loops. However, most mechanistic evidence derives from young adult populations, and direct age-comparative studies remain sparse. This developmental framework should therefore be regarded as a working hypothesis requiring validation through lifespan-specific research (Fig. 2).

Fig. 2.

Hypothesised model of lifespan trajectories of the sleep–pain relationship. The figure depicts a proposed working model of how sleep and pain interact across development. Early-life immaturity of sleep and pain systems confers vulnerability; in adolescence, circadian misalignment and emotional dysregulation heighten risk; in adulthood, lifestyle and comorbidities reinforce the cycle; and in older age, degenerative and sleep-architecture changes sustain bidirectional feedback. Red loops indicate that sleep tends to precede pain in youth but may become a reciprocal process in later life, identifying key periods for intervention. HPA, hypothalamic-pituitary-adrenal axis; OSA, obstructive sleep apnoea; RLS, restless legs syndrome.

Sleep and pain across the lifespan

Sleep and pain are intertwined across all stages of life,⁶⁵ though the nature of this relationship may evolve with developmental and biological changes (Fig. 2).

Early life and childhood

Sleep and pain regulation undergo significant maturation in early life. Infants have polyphasic sleep with high REM content, which gradually consolidates into circadian rhythms by early childhood. Pain modulation systems also develop over time; descending inhibitory pathways mature slowly, reaching adult-like function only by pre-adolescence.⁶⁶ This developmental window may contribute to pain vulnerability, as young children have less capacity to dampen pain signals, especially when sleep is disrupted.

Prospective studies suggest that childhood sleep problems can predict later chronic pain. In the Adolescent Brain Cognitive Development (ABCD) study (∼12,000 US children), self-reported sleep disturbances at ages 9–10 significantly increased the odds of developing new multisite pain after one year.⁷ In this study, each increment in baseline sleep problems was associated with about 20% higher odds of developing multisite pain one year later. Notably, these children were pain-free at baseline, strengthening the case that poor sleep preceded the onset of pain rather than merely accompanying it. Similar findings from an Australian cohort link childhood sleep difficulties to greater pain during the transition to adolescence,⁶⁷ and self-reported sleep problems also predicted chronic back pain in the cross-national Health and Behaviour of School-Aged Children (HBSC) study.⁶⁸ However, these cohort studies relied on self-rated sleep quality, rather than objective sleep measures such as PSG; thus it remains uncertain which elements of sleep physiology are most relevant for future pain. Additionally, despite their temporal sequencing, the observational nature of these studies precludes definitive causal inference as they are susceptible to confounding and other biases. Experimental sleep restriction studies in children would help clarify causality but face ethical constraints.

Family and environmental factors may play a role in the sleep–pain relationship. In the ABCD study, childhood adversity and household stress disrupt sleep and were associated with higher pain risk in adolescence.⁶⁹ Parental sleep and pain behaviours may model unhealthy patterns, while chaotic routines and socioeconomic strain can further impair a child's sleep and stress regulation. Biologically, sleep supports neurodevelopment in brain regions crucial for emotion and pain modulation. Persistent sleep loss during this period may weaken these systems, increasing susceptibility to chronic pain.

Importantly, chronic pain that begins in youth often persists into adulthood. Over 80% of adolescents with juvenile-onset fibromyalgia continue to experience symptoms as adults,⁷⁰ and up to two-thirds of children with chronic abdominal pain report ongoing or migrating pain in later life.⁷¹ These findings underscore childhood as a critical window for altering the trajectory of chronic pain, beginning with sleep.

Adolescence and young adulthood

Biological and epidemiological context

Adolescence brings a natural circadian phase delay, with melatonin release shifting 1–3 h later, shifting the internal clock forward relative to the standard day–night cycle,⁷² leading teens to fall asleep later and experience chronic sleep restriction, especially with early school start times. Most adolescents fail to meet the recommended 8–10 h of nightly sleep,⁷³ resulting in widespread sleep deficiency during a critical period of neurodevelopment.⁷⁴

Against this backdrop of biological sleep disruption, chronic pain prevalence also rises, affecting 20–25% of teens.⁷⁵ Conditions like back pain, headaches, and abdominal pain are particularly common among girls.^68,76 Evidence from the aforementioned HBSC survey suggests this burden may be increasing: chronic back pain prevalence rose from 18% in 2002 to 22% in 2018, a trend potentially mediated by worsening sleep.⁶⁸ The temporal coincidence of adolescent sleep disruption and rising pain prevalence raises the question: does poor sleep contribute to pain onset in adolescence?

Temporal relationships: sleep as a predictor of pain

Multiple prospective cohort studies suggest sleep disturbance precedes and predicts chronic pain development in adolescents. In a Dutch cohort of ∼1750 emerging adults (ages 19–22), severe baseline sleep problems tripled the risk of developing chronic pain over three years (38% versus 14% in those without sleep issues).⁷⁶ This relationship was stronger in females and showed dose–response characteristics. Of note, baseline pain had limited predictive value for later sleep issues. Another longitudinal study of 2767 Swedish teenagers reported similar findings.⁷⁷ In the clinical setting, among adolescents undergoing major musculoskeletal surgery, pre-operative sleep quality predicted pain trajectories at 12-month follow-up, even after adjusting for baseline pain and psychosocial factors.⁷⁸

While these studies provide consistent temporal evidence, there are methodological limitations similar to those discussed earlier for other observational studies. Limited experimental evidence partially addresses these limitations. In a three-week crossover randomised trial (n = 31), sleep extension interventions improved pain in adolescents with juvenile idiopathic arthritis.⁷⁹ However, the study is limited by small sample size, short duration, and homogeneous population. Whether sleep interventions prevent pain onset in pain-free adolescents, or benefit other pain conditions with sustained effects, remains to be established.

Mechanisms: neurobiology, mood, and lifestyle

Several interacting mechanisms may explain why adolescent sleep loss increases pain vulnerability. Experimentally, sleep deprivation reduces pain thresholds in healthy volunteers,⁸⁰ and over half of adolescents with chronic pain self-report significant sleep disturbance.⁸¹ During adolescence, when pain modulatory and mood-regulatory circuits are still developing, chronic sleep loss may hard-wire maladaptive responses through heightened inflammatory signalling and altered central sensitisation.

Psychosocial and lifestyle factors likely amplify biological vulnerabilities. Modern adolescent lifestyles, characterised by late-night screen use, academic pressures, and irregular schedules, further erode sleep and may contribute to pain risk.⁸² Technology delays circadian rhythms and displaces sleep, while mental health issues such as anxiety and depression, which often emerge in adolescence, create bidirectional feedback loops. Depression frequently co-occurs with both chronic pain and insomnia, potentially through shared pathways including limbic hyperactivity, HPA axis dysregulation, and perseverative cognition.⁸³

Supporting the role of mood, a longitudinal study of 2767 adolescents found that depressive and anxious symptoms mediated the pathway from poor sleep to pain, but not vice versa.⁷⁷ This suggests mood dysregulation may be an intermediary through which sleep disruption leads to pain. Consistent with this, animal models show that early-life stress produces enduring alterations in sleep-reward coupling and affective regulation,⁸⁴ though this has not been translated to human adolescent populations.

Shift work and emerging adulthood

In young adulthood, occupational factors introduce new sleep-pain risks. Shift work disrupts circadian rhythms and may increase pain sensitivity. In a small crossover study, night-shift workers (n = 19) showed greater sensitivity to experimental pain than day-workers.⁸⁵ However, large observational cohorts show mixed findings: a 7-year Norwegian follow-up study (n = 2323) found no increase in chronic pain among shift workers unless accompanied by elevated inflammatory markers.⁸⁶ This suggests shift work may act as a conditional risk factor, potentiating pain risk in vulnerable individuals rather than causing pain directly.

Implications for prevention and future research

Adolescence and young adulthood represent critical windows for intervention. While current evidence is limited by reliance on observational designs, findings are consistent across multiple cohorts. Interventional trials targeting sleep, such as delaying school start times, improving sleep hygiene, or treating insomnia pharmacologically or with CBT-I, may clarify causal relationships and reduce chronic pain risk, particularly in females who show stronger sleep-pain associations.^67,76 Addressing sleep proactively in youth could alter pain trajectories before they become entrenched later in adulthood.

Midlife to older adulthood

Epidemiology and shifting directionality

Both chronic pain and sleep problems increase with age. Chronic pain prevalence rises from ∼13% in US adults aged 25–44 to ∼28% in those aged 65–84, driven by degenerative conditions such as arthritis and neuropathies.⁸⁷ Similarly, nearly 50% of older adults report chronic sleep difficulties,⁸⁸ with approximately 40% experiencing difficulty initiating or maintaining sleep.⁸⁹ These conditions frequently co-occur: half to three-quarters of older adults with chronic pain also report insomnia.²

Importantly, the directionality of the sleep–pain relationship may shift in later life. While evidence in younger populations suggests sleep disturbance predominantly precedes pain, the relationship in older adults appears more bidirectional and self-reinforcing. Pain disrupts sleep continuity, while poor sleep lowers pain thresholds, creating a vicious cycle. However, disentangling this relationship is methodologically challenging, as many older adults have longstanding sleep and pain by the time they are studied. The extent to which this apparent bidirectionality reflects true mechanistic shifts versus cumulative burden remains unclear.

Mechanisms: sleep architecture, inflammation, and comorbidity

Several age-related changes may explain increasing sleep-pain interdependence. Aging alters sleep architecture, with progressive reductions in SWS and increased fragmentation.⁹⁰ Loss of deep sleep impairs tissue repair and inflammatory regulation, potentially weakening pain inhibition. Cross-sectional studies in older adults with osteoarthritis show associations between reduced SWS, elevated inflammatory markers (CRP, IL-6), and greater pain,^91,92 though these observational findings cannot establish causality. Similarly, a large cross-sectional analysis of UK Biobank participants found that individuals with chronic musculoskeletal pain had both worse self-reported sleep and higher CRP levels, with inverse associations between sleep quality and inflammation.⁹³ While suggesting inflammation as a potential common pathway, the cross-sectional design precludes causal inference.

Accumulating comorbidities may further contribute to the sleep–pain relationship. Obesity, cardiovascular disease, sleep-disordered breathing, and movement disorders (e.g. restless legs syndrome) are prevalent and associated with both sleep disruption and pain. These conditions are particularly common in rheumatological disorders, and may contribute to the sleep disturbance observed.⁹⁴ Depression, affecting up to 20% of older adults, frequently co-occurs with both pain and insomnia.⁹⁵

Interventions and evidence gaps

Despite this complexity, interventions targeting sleep and pain may yield benefits. For sleep-focused approaches, a small pilot study (n = 33) indicated that CBT-I may restore SWS and reduce pain in older adults with osteoarthritis,⁹⁶ though replication in adequately powered trials is needed. Conversely, the impact of treating pain on sleep quality is also under-studied. Some analgesics used in chronic pain management may benefit sleep architecture (e.g. pregabalin, amitriptyline), while others, notably opioids, appear to worsen sleep quality.⁹⁷ It remains uncertain whether sleep-focused interventions can prevent pain onset or whether pain-focused treatments meaningfully improve sleep. Managing comorbid sleep disorders represents another logical target, though intervention studies with pain outcomes are lacking.

Sleep measurement and interventions in chronic pain

Measuring sleep accurately is crucial for delineating how pain alters sleep physiology and perception. Both objective and subjective methods are used in pain research and clinical practice, each capturing different facets of sleep, such as continuity, architecture, and circadian timing.

Sleep measurement in chronic pain

The gold standard for sleep assessment is polysomnography (PSG), a laboratory-based test capturing electroencephalography (EEG), electrooculography, electromyography, electrocardiography, respiratory effort, airflow, and blood oxygenation. PSG enables precise sleep staging and the identification of sleep architecture. Yet, it is burdensome for patients with chronic pain, who may struggle with the physical discomfort and artificial laboratory-based sleep environment.^98,99

In fibromyalgia, PSG reveals hallmark abnormalities: alpha-delta intrusion during NREM sleep, decreased delta amplitude, and reduced REM and SWS.³¹ Bjurstrom and Irwin summarise PSG characteristics in different chronic pain conditions, with alterations of sleep continuity being commonly reported.⁹⁸

Portable, home-based, alternatives have gained popularity. Actigraphy, a wrist-worn accelerometer-based method, estimates sleep-wake patterns over extended periods and is better tolerated than PSG. Though it lacks the resolution to distinguish sleep stages,¹⁰⁰ it is widely used in pain and sleep research. Machine learning on actigraphy data can be used to predict chronic pain from circadian dysregulation.¹⁰¹ Additionally, actigraphy data and questionnaires used in a cross-sectional study of adult cancer patients (n = 68) showed that pain is a mediator between rest/activity rhythms and sleep disturbance.¹⁰² Actigraphy's accuracy improves when paired with autonomic markers like heart rate variability.¹⁰³ Dudarev and colleagues found that nighttime heart rate predicted next-day pain in fibromyalgia and low back pain, even after controlling for concurrent HRV, pain on the previous day, and analgesia use.¹⁰⁴ Other non-intrusive tools include EEG headbands,¹⁰⁵ skin patches,¹⁰⁶ rings,¹⁰⁰ and in-ear EEG.¹⁰⁷ These methods show promise, with some nearing PSG-level accuracy. Mattress sensors offer another avenue for sleep tracking, though stage-level precision remains limited.¹⁰⁸

Self-report measures remain important and are the most widely employed measures of sleep in clinical practice and research. Questionnaires such as the Insomnia Severity Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale complement objective methods. For children, tools like the Children's Report of Sleep Patterns and Paediatric Sleep Questionnaire are available.¹⁰⁹ Sleep diaries, while widely used, may diverge from actigraphy-based results, capturing different aspects of sleep.¹¹⁰

While validated sleep measures exist for both children and older adults, few have been specifically validated in chronic pain patients. In paediatric samples, tools such as the Children's Sleep Habits Questionnaire¹¹¹ and Children's Report of Sleep Patterns¹¹² are commonly used, though their psychometric performance in pain contexts remains underexplored. In geriatric populations, instruments like the Pittsburgh Sleep Quality Index and Consensus Sleep Diary are frequently applied, yet normative thresholds may be confounded by age-related sleep changes and multimorbidity.¹¹³ The development and validation of age- and pain-specific sleep assessment tools represent important priorities for future research.

Interventions

Despite the impact of sleep disturbances on quality of life in patients with chronic pain, the effects of sleep treatment on pain are mixed.

Behavioural and psychological interventions

CBT-I is the most studied treatment for sleep disturbance in chronic pain. A systematic review and meta-analysis of 12 RCTs (n = 762) found CBT-I was associated with improvements in self-reported sleep, pain, and depression in chronic pain populations.³⁶ However, as discussed earlier, effects on pain were modest (SMD 0.17–0.20) and short-lived compared to robust and durable sleep improvements (SMD 0.56–0.89). This may reflect unrecognised heterogeneity in chronic pain mechanisms. For instance, some patients with osteoarthritis exhibit predominant nociceptive features while others show nociplastic characteristics,¹¹⁴ though whether treatment response differs by phenotype remains unstudied.

Sleep hygiene strategies, including addressing bedtime routines, alcohol, caffeine, and screen use, are widely recommended but under-tested in pain cohorts. A scoping review identified six strategies with potential benefit (education, exercise, limiting alcohol use, limiting tobacco use, pre-bed state and sleep environment), though timing and consistency of implementation remain poorly reported.¹¹⁵ Chronotherapy, such as morning light exposure, may help stabilise sleep-wake cycles and reduce symptom severity, but remains under-studied.¹¹⁶

Pharmacological approaches

Pharmacological therapy should be used judiciously in both pain and sleep management. Opioids remain widely prescribed in chronic pain, yet their efficacy, especially in older adults, is unclear and they are not recommended as first line treatment.¹¹⁷ Moreover, their use is associated with sleep disruption.^97,118

Some medications may benefit both sleep and pain. Tricyclic antidepressants such as amitriptyline, and anticonvulsants such as pregabalin, have been used to address both pain and sleep complaints, but require caution due to potential adverse effects.¹⁰ A novel form of sublingual cyclobenzaprine demonstrated significant improvements in both daily pain and sleep quality in fibromyalgia in a recent phase III RCT (n = 503), with benefits thought to be mediated by enhanced sleep quality.¹¹⁹ Melatonin showed short-term improvements in sleep quality at 3 weeks in a randomised trial of patients with severe chronic pain (n = 60), though benefits were not sustained at 6 weeks and pain improved equally with placebo.¹²⁰ Orexin antagonists offer another approach, with early trials indicating improved sleep but mixed effects on pain.¹²¹ Optimising circadian timing of analgesics may enhance efficacy, given that many drug targets exhibit diurnal variation, but supportive clinical trial evidence is limited.¹²²

Lifespan-specific considerations

Treatment approaches should be adapted to age and developmental stage, as both vulnerability and treatment response shift across the lifespan. As outlined in earlier sections, sleep disturbance in youth often precedes pain onset, whereas in older adults the relationship may become more bidirectional. Accordingly, interventions should serve different goals: prevention and early intervention in youth, versus symptom management and breaking feedback loops in older age.

Children and adolescents

In paediatric and adolescent pain, early intervention is important for both symptom relief and long-term prevention of chronic pain and resulting disability. Sleep assessment typically relies on validated questionnaires and, where needed, wearables; full PSG is reserved for complex cases. Non-pharmacological treatment strategies are preferred; CBT for pain increasingly incorporates sleep-focused elements, and there is growing momentum for fully integrated CBT-I or hybrid models in teens with comorbid insomnia. Digital tools (e.g. digital CBT-I) are particularly promising in this group. Parents play a key role in reinforcing healthy routines, limiting screen time, and discouraging maladaptive habits like co-sleeping or excessive napping. Melatonin is also commonly used due to its favourable safety profile and circadian effects.

Adults and older adults

In working-age adults, behavioural therapies such as CBT-I and sleep hygiene often pair well with lifestyle changes and are generally well tolerated. In older adults, sleep problems are compounded by changes in sleep architecture, multimorbidity, and medication burden. Treatment must balance benefit with safety: low-dose tricyclic antidepressants or melatonin may be considered, while sedatives should be used cautiously. CBT-I can still improve deep sleep and pain in older adults, with caregiver involvement to improve adherence and outcomes. Addressing relevant comorbid sleep disorders is especially valuable in older age.

Outstanding questions

Despite strong evidence linking sleep and chronic pain, key questions remain.

Prevention and early intervention

One major gap is whether improving sleep early in life can prevent later chronic pain. Animal studies suggest early life sleep disruption alters pain sensitivity in later life,¹²³ but prospective human studies tracking sleep interventions from childhood through adulthood are lacking. Similarly, whether adolescent sleep deprivation or shift work in young adulthood increases long-term pain risk remains unknown. As discussed above, the effect of pain on long-term sleep outcomes is also uncertain, and whether treating pain can improve sleep should be an area of future study. Addressing these questions will require long-term cohort studies across the lifecycle and early intervention trials.

Optimising treatment through phenotyping

Another challenge is understanding why sleep interventions yield inconsistent pain outcomes in trials. CBT-I and other therapies often improve sleep, but pain relief is variable.^36,124 This heterogeneity likely reflects multiple factors. First, pain mechanisms vary even within diagnostic categories; for instance, some patients with osteoarthritis exhibit predominantly nociceptive features while others show nociplastic characteristics,¹¹⁴ yet few trials stratify by pain phenotype. Second, sleep disturbance itself is multidimensional, ranging from short sleep, fragmentation, poor sleep quality, to altered sleep architecture, and each may engage different biological pathways. Fragmented sleep may impair glymphatic clearance and amplify central inflammation, potentially worsening nociplastic pain. Short sleep duration, on the other hand, is associated with systemic inflammation, which may drive nociceptive pain.¹²⁵ Third, neuropathic pain may involve both central and peripheral processes, making it susceptible to multiple sleep-related mechanisms. Future trials should phenotype both sleep architecture (e.g. using PSG) and pain mechanisms to identify which sleep deficits most strongly impact which pain types, and whether targeted interventions (e.g. SWS enhancement for nociplastic pain) improve outcomes.

Understanding mechanisms

Understanding bidirectional mechanisms remains challenging. While evidence suggests sleep disturbance often precedes pain in youth, the relationship in older adults appears more reciprocal. Whether treating pain improves sleep, and through which mechanisms, is understudied. Similarly, whether specific sleep dimensions (e.g. REM disruption, circadian misalignment) differentially affect pain trajectories across the lifespan requires investigation. Integrating sleep and pain assessment across developmental stages within the same cohort would clarify how these relationships evolve with age.

Methodological limitations

Finally, the evidence for age-dependent shifts in sleep-pain directionality is preliminary. The developmental trajectories in sleep-pain directionality we describe are inferred largely from parallel literatures conducted in different age groups rather than demonstrated through direct age comparisons using comparable methods. Longitudinal studies spanning multiple decades with standardised sleep and pain assessment are needed to validate the lifespan framework.

Conclusion

This review proposes that sleep–pain relationships evolve across the lifespan, with sleep disruption potentially predisposing to pain in youth, while bidirectional interactions may predominate in later life. However, evidence for these developmental shifts remains preliminary. Clinically, this underscores the need for age-tailored sleep interventions in pain management. From a research perspective, important gaps remain: we require better phenotypic characterisation of sleep disturbances and pain mechanisms at different ages, prospective longitudinal studies spanning multiple life stages, and adequately powered clinical trials testing both sleep interventions with pain outcomes and pain interventions with sleep outcomes. Improving sleep offers a promising modifiable target for preventing and managing chronic pain throughout life, but realising this potential requires developmentally informed, mechanistically grounded approaches.

Contributors

EK and AW conceptualised the study and conducted the literature search. EK drafted the initial manuscript. EK and AW contributed to manuscript writing and revisions. BS and AI provided oversight and supervision and reviewed all versions of the manuscript. All authors critically reviewed the content and approved the final version of the manuscript.

Declaration of interests

The authors have no interests to declare.