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

Sleep quality is often compromised in individuals with chronic pain conditions such as fibromyalgia, burn injuries, and back pain. A substantial percentage (at least 50%) of chronic pain patients report sleep disturbances, which are also predictive of new pain incidents and symptom worsening. While the precise mechanisms underlying the relationship between sleep disturbances and pain are unclear, brain regions like the periaqueductal gray (PAG) and raphe nuclei are implicated in both sleep regulation and nociception. Overlapping functions in these areas may explain the link between sleep loss and reduced pain inhibition. Mechanistic pain profiling, encompassing pain thresholds, TSP, and CPM, helps assess pain mechanisms in the peripheral and central nervous systems. TSP reflects central sensitization (wind-up), while CPM reflects descending pain inhibition. Impaired CPM is associated with various chronic pain conditions and predicts poor treatment response. Previous research on TSD's effects on pain sensitivity has yielded mixed results, with some studies reporting increased thermal and pressure pain sensitivity, while others found no significant changes in heat pain thresholds. This study aimed to examine the effects of 24 hours of TSD on peripheral and central pain mechanisms in healthy participants, using quantitative sensory testing (QST) and measures of TSP and CPM to assess pressure and thermal pain sensitivity.

The literature shows a strong correlation between sleep disturbances and chronic pain. Studies across various chronic pain conditions (fibromyalgia, burn injuries, back pain) report a high prevalence of sleep problems among patients. These sleep problems are not only co-occurring symptoms but also predictors for the onset and worsening of chronic pain. The mechanisms connecting sleep and pain are complex but may involve the PAG and raphe nuclei, areas in the brain that play crucial roles in both pain modulation and sleep-wake cycles. These structures, sharing common neurotransmitters and pathways, may explain the observed relationship between sleep quality and pain inhibition. Mechanistic pain profiling, a standardized approach used to determine the contribution of peripheral and central nervous system mechanisms to the pain experience, has revealed a link between impaired descending pain inhibition (reflected by impaired CPM) and chronic pain states. Previous studies show inconsistent results about the impact of TSD on pain perception, particularly in thermal pain thresholds, highlighting the need for further clarification.

Twenty-five healthy participants (nine women, average age 22.6 years) were recruited. One participant was excluded due to an undisclosed history of mental illness, leaving 24 participants (eight women) for analysis. The study employed a two-session design, separated by 24 hours of TSD. TSD compliance was monitored via hourly text messages. The study included questionnaires assessing sleep quality (PSQI) and pain catastrophizing (PCS) before baseline. QST, using the Medoc pathway system, assessed cold and warm detection thresholds (CDT, WDT) and cold and heat pain thresholds (CPT, HPT). A cuff algometer assessed pressure pain detection thresholds (cPDTs), tolerance thresholds (cPTTs), TSP, and CPM. TSP was evaluated using a mechanical pressure stimulus at the cPTT level, applied ten times with 1-second intervals. Pain intensity was rated using a visual analogue scale (VAS). CPM was assessed by comparing cPDT with and without a conditioning stimulus (70% of cPTT applied to the non-dominant leg). Paired sample t-tests or Wilcoxon signed-rank tests (depending on data distribution) compared pre- and post-TSD measurements. Bonferroni correction was applied for multiple comparisons.

After 24 hours of TSD: * No significant changes were observed in CDT and WDT. * CPT significantly decreased (indicating increased cold pain sensitivity). * HPT showed no significant change. * cPDT and cPTT significantly decreased (indicating reduced pressure pain detection and tolerance). * TSP was significantly facilitated (indicating increased central sensitization). * CPM was significantly impaired (indicating reduced descending pain inhibition). The cPDT increased significantly with conditioning stimulus at baseline, but not after TSD.

This study provides the first evidence that 24 hours of TSD impairs CPM, facilitates TSP, and increases sensitivity to pressure and cold pain in a single experimental setup. These findings demonstrate that TSD affects both central and peripheral pain processing. The impairment of CPM suggests a disruption of descending inhibitory pathways, while the facilitated TSP points to increased spinal excitability and central sensitization. The increased sensitivity to pressure and cold pain indicates peripheral sensitization. The findings support the hypothesis that sleep loss exacerbates pain by disrupting multiple pain processing mechanisms. These results highlight the importance of addressing sleep disturbances in the management of chronic pain. Future research should investigate whether sleep interventions can reverse these TSD-induced alterations in pain processing.

This study demonstrates that total sleep deprivation (TSD) significantly alters pain processing in healthy individuals, impairing conditioned pain modulation, facilitating temporal summation of pain, and increasing sensitivity to pressure and cold pain. This suggests TSD affects both central and peripheral pain pathways. Future research should focus on the underlying mechanisms of these effects and on whether sleep therapy can reverse these changes, potentially leading to novel pain management strategies for chronic pain patients.

The study's reliance on hourly text messages for TSD monitoring doesn't guarantee complete sleep deprivation. Participants had relatively low sleep quality and duration before the baseline session, potentially influencing their response to TSD. Future research should consider more rigorous TSD monitoring methods and recruit participants with better baseline sleep quality to enhance the study's generalizability.