Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants

Sleep disturbances are highly prevalent among individuals with chronic pain (e.g., fibromyalgia, burn injuries, back pain), and impaired sleep is associated with increased pain sensitivity and poorer outcomes. Overlapping brain regions involved in sleep regulation and pain modulation (periaqueductal gray, raphe nuclei, ascending reticular activating system) suggest a mechanistic link between sleep loss and altered pain processing. Mechanistic pain profiling using temporal summation of pain (TSP) and conditioned pain modulation (CPM) provides surrogate markers of central sensitization (wind-up) and descending inhibitory control, respectively. Prior evidence indicates that CPM is impaired in several chronic pain conditions and following sleep impairment, while findings for TSP and thermal hyperalgesia after sleep loss are mixed. The present study aimed to determine, in healthy participants, whether 24 hours of total sleep deprivation (TSD) alters peripheral pain sensitivity (thermal and pressure thresholds) and central pain mechanisms (TSP and CPM).

Multiple studies report bidirectional links between poor sleep and heightened pain. Impaired CPM has been observed in patients with back pain, fibromyalgia, osteoarthritis, rheumatoid arthritis, temporomandibular disorders, and after experimentally fragmented sleep. Evidence regarding TSP after sleep impairment is inconsistent; some work shows facilitated TSP with disrupted sleep or altered REM, while others report no changes, possibly due to modality differences (pressure/A-fiber vs heat/C-fiber). Prior TSD studies generally show increased mechanical and thermal pain sensitivity, though findings for heat and cold thresholds vary. Meta-analytic data support that sleep loss increases pain sensitivity across modalities. Methodological heterogeneity in CPM paradigms (e.g., cuff algometry vs cold pressor) may contribute to mixed findings across studies.

Design: Two-session within-subject trial with assessments after a habitual night of sleep (baseline) and after 24 hours of total sleep deprivation (post-TSD). Sessions occurred on consecutive days; participants sent hourly text messages overnight to promote wakefulness. Experimental modalities were applied in a fixed order across both sessions: heat, cold, pressure, TSP, CPM. Participants: 25 recruited; 24 healthy adults (8 women; mean age 22.6 ± 2.04 years) completed. Exclusion for undisclosed mental illness (n=1). Ethics approval (N-20180089) and informed consent obtained. Questionnaires: Pittsburgh Sleep Quality Index (PSQI) and Pain Catastrophizing Scale (PCS) at baseline; participants reported sleep duration and quality before baseline. Baseline cohort characteristics included PSQI (5.04 ± 1.71), sleep duration 6.85 ± 1.11 h (night before baseline) and habitual 7.25 ± 0.69 h. Thermal quantitative sensory testing: Using Medoc Pathway with 3×3 cm ATS probe on volar forearm (3 cm below elbow). Baseline temperature 32°C; ramp 1°C/s; cutoffs 0–50°C. Three repetitions averaged per measure. Cold and warm detection thresholds (CDT, WDT): press at first sensation of cool/warm. Cold and heat pain thresholds (CPT, HPT): press at first pain. Pressure/cuff algometry: Cuff on gastrocnemius belly; inflation rate 1 kPa/s; maximum 100 kPa; continuous VAS pain ratings. Cuff pressure pain detection threshold (cPDT) defined at VAS 1 cm; tolerance (cPTT) at unbearable pain. Determined on dominant leg. Temporal summation of pain (TSP): Ten mechanical pressure pulses (1 s duration, 1 s interstimulus interval) at intensity equal to each participant’s cPTT; continuous VAS ratings. TSP quantified as difference between mean VAS of last three pulses and first three pulses. Conditioned pain modulation (CPM): Conditioning stimulus: cuff on non-dominant leg inflated promptly to 70% of cPTT. Test stimulus: cPDT on dominant leg with inflation at 1 kPa/s. CPM effect calculated as difference in cPDT with vs without conditioning stimulus. Statistics: SPSS v25. Paired t-tests compared pre- vs post-TSD for each parameter (WDT, CDT, HPT, CPT, cPDT, cPTT, TSP, CPM). If assumptions violated, Wilcoxon signed-rank test used. Bonferroni correction applied for CPM comparisons (alpha 0.025). Overall significance P < 0.05. Data reported as mean ± SD. Thermal data analyzed for n=23 (one technical failure); pressure/TSP/CPM n=24.

- Thermal detection thresholds: No significant changes from baseline to post-TSD. • CDT: baseline 29.5 ± 1.03°C vs post 29.0 ± 1.3°C; t = 1.36, p = 0.19. • WDT: baseline 34.6 ± 0.77°C vs post 34.7 ± 1.24°C; z = 0.99, p = 0.32. - Thermal pain thresholds: • Cold pain threshold (CPT) significantly changed consistent with increased cold pain sensitivity after TSD (reported as decreased CPT): baseline 12.1 ± 8.9 vs post 15.6 ± 8.51; z = 2.3, p = 0.02. • Heat pain threshold (HPT): no significant change; baseline 44.6 ± 2.7°C vs post 44.1 ± 2.7°C; t = 0.96, p = 0.35. - Pressure pain: • cPDT decreased after TSD (greater sensitivity): baseline 42.13 ± 10.45 kPa vs post 38.8 ± 11.85 kPa; t = 2.22, p = 0.037. • cPTT decreased (lower tolerance): baseline 87.83 ± 14.45 kPa vs post 83.9 ± 17.11 kPa; z = -2.11, p = 0.03. - Temporal summation of pain (TSP): significantly facilitated post-TSD: baseline 1.59 ± 1.23 VAS vs post 2.27 ± 1.66 VAS; t = -2.68, p = 0.01. - Conditioned pain modulation (CPM): • Baseline: cPDT increased with conditioning vs without (effective CPM): t = -3.63, p = 0.002 (Bonferroni-corrected). • Post-TSD: no significant increase in cPDT during conditioning (impaired CPM): t = -1.81, p = 0.168 (Bonferroni-corrected). Overall, 24 hours of total sleep deprivation increased mechanical and cold pain sensitivity, impaired descending inhibitory control, and enhanced central sensitization as indexed by TSP.

Findings demonstrate that a single night of total sleep deprivation negatively affects both central and peripheral pain processes in healthy adults: CPM was impaired (suggesting reduced descending inhibitory control), TSP was facilitated (indicative of increased central sensitization), and sensitivity to pressure and cold pain increased. These results align with literature linking poor sleep to diminished endogenous pain inhibition and generalized hyperalgesia, although prior CPM/TSP studies have reported mixed outcomes likely due to methodological heterogeneity (e.g., conditioning/test stimuli differences such as cuff algometry versus cold pressor, and pain modality targeting distinct nociceptor pathways). The overlap of neural substrates involved in sleep-wake regulation and pain modulation (periaqueductal gray, raphe nuclei, ARAS) offers a biological basis for sleep-loss–induced alterations in pain processing. Clinically, the results support the rationale for assessing and treating sleep problems to improve pain modulation and reduce hyperalgesia.

The current study is the first to demonstrate that total sleep deprivation impairs conditioned pain modulation, facilitates temporal summation of pain, and increases pain sensitivity to pressure and cold pain stimuli in healthy participants, indicating that sleep loss affects both central and peripheral pain pathways. Future research should elucidate the mechanisms underlying these changes, their impact on the central and peripheral nervous system, and whether they are reversible with sleep therapy.

TSD was monitored via hourly text messages, which cannot fully exclude brief sleep episodes. Participants showed modestly reduced sleep quality (PSQI > 5 on average) and somewhat short prior-night sleep at baseline, potentially making them less sensitive to the effects of TSD; nevertheless, significant central and peripheral effects were observed. A sample with higher baseline sleep quality/duration might exhibit even greater hyperalgesic responses.