Pain perception, brain activity, and management in individuals with chronic pain and Insomnia

Abstract

Sleep disturbance is commonly complaint among individuals with chronic pain, may exacerbate pain intensity, and cause functional impairment and poor prognosis. Although the interaction between disrupted sleep and pain is well documented, the underlying mechanisms for this relationship remain insufficiently understood. Growing attention has been directed toward changes in both peripheral and central mechanisms of pain regulation, yet the neurophysiological mechanisms linking sleep and pain in clinical populations are still not fully understood. Furthermore, the prospective relationship between these two conditions remains uncertain, particularly whether changes in sleep are correlated with corresponding changes in pain-related outcomes. More importantly, there is limited evidence identifying the most effective non-pharmacological treatments for enhancing sleep in people with chronic pain and how existing treatment protocols could be optimized for those with comorbid chronic pain and insomnia. This project used three systematic reviews, a cross-sectional study, and a pilot randomized controlled trial to address these research gaps. The first systematic review and meta-analysis revealed that sleep loss led to heightened pain perception. However, different sleep deprivation paradigms had varying effects on subjective pain intensity and the exacerbation of peripheral or central pain sensitization in healthy individuals. Our cross-sectional study using quantitative sensory testing and resting-state electroencephalography to investigate pain perception and neural oscillatory patterns among females with chronic low back pain (CLBP), insomnia, comorbid conditions, or neither. The results found that individuals with comorbid CLBP and insomnia showed significantly reduced pressure pain thresholds at the back, greater impairment in descending pain modulation, altered functional connectivity across multiple brain networks compared to tother groups. More importantly, insomnia remained to be independently linked to lower mechanical pain threshold and aberrant functional connectivity in the comorbid group, after adjusting for pain-related factors and psychological variables. The second systematic review showed better self-reported sleep quality and longer total sleep time were significantly linked to reductions in pain severity and improvements in disability among individuals with CLBP. The third systematic review and network meta-analysis found that among 14 identified non-pharmacological interventions, eight showed significantly greater improvements in sleep quality immediately after treatment compared to passive control in individuals with chronic musculoskeletal pain. Our a pilot randomized controlled trial showed that repetitive transcranial magnetic stimulation (rTMS) was a feasible and acceptable treatment for comorbid conditions. Both active stimulation protocols significantly reduced pain intensity and enhanced descending pain inhibitory function compared to sham stimulation. Importantly, only rTMS targeting the left dorsolateral prefrontal cortex significantly improved insomnia severity and reduced objective wake after sleep onset. In summary, this project has advanced our understanding of the complex interplay between sleep disturbance and chronic pain. These results emphasize the critical importance of integrating sleep assessment and treatment into pain management strategies. Future research should aim to elucidate the underlying mechanisms further and evaluate the effectiveness of personalized, biomarker-informed treatment approaches. Such efforts may significantly advance our understanding of the interactions between these two conditions and improve the sleep and pain management in these complex populations.