Thermal Pain Sensitivity is Driven by Circadian Rhythms
Post by Lincoln Tracy
The takeaway
Keeping patients awake for an extended period in a highly controlled environment reveals thermal pain sensitivity is driven by circadian rhythms, with the peak in pain sensitivity occurring between 3:00-4:30 am.
What's the science?
How intense we perceive a painful sensation to be, changes throughout the day. It’s possible this variation is related to our internal circadian clock (or rhythm), but the exact reason is unknown. This week in Brain, Daguet, and colleagues used a highly-controlled constant-routine protocol to determine whether sensitivity to thermal pain displays rhythmic changes over a 24-hour period and assess the specific contributions of the circadian clock and other sleep-related processes to the potential change in thermal pain sensitivity.
How did they do it?
The authors recruited 12 healthy males (mean age 22.7 years) who maintained a regular sleep/wake schedule for three weeks before entering the laboratory to complete the 56-hour experimental protocol. The participants arrived at about 10 am on the first day and familiarized themselves with the dark laboratory environment which was free of external time cues (e.g., clocks, television, and visitors). Participants slept for eight hours in darkness as per their normal sleeping habits. Once they awoke on the second day, participants were kept awake for the next 34 hours until the end of the experiment (approximately 6 pm on day three). Salivary melatonin levels were assessed hourly during the 34-hour awake period; thermal heat pain sensitivity, body temperature, and heart rate were evaluated every two hours. Specifically, the authors tested participants’ heat detection threshold (the point at which they felt a warm sensation), heat pain threshold (the point at which the stimulus became painful), and sensitivity to 42°C, 44°C, and 46°C stimuli at these intervals. The authors then explored if and how pain sensitivity and the collected physiological measures changed over time.
What did they find?
First, the authors found that pain sensitivity increased with sleep debt, with the 44°C and 46°C thermal stimuli (but not the 42°C stimuli) being rated as more painful the longer the participant was kept awake. This suggests the known relationship between sleep deprivation and pain sensitivity may not apply to lower levels of pain. Second, they found pain sensitivity is driven primarily by circadian rhythms, rather than by sleep pressure. Instead of simply steadily increasing as sleep deprivation increased over the 34-hour time period, the peak in pain sensitivity occurred between 3:00 am and 4:30 am. Third, they found the peak in pain sensitivity occurred at a similar time to the troughs (low point) in body temperature and heart rate (3:00 and 2:00 am, respectively). In addition, pain sensitivity peaked one and a half hours after the peak in melatonin secretion (2:00 am). These findings imply a phase relationship between the circadian components of pain modulation and other physiological rhythms.
What's the impact?
The results of this study demonstrate that pain sensitivity is driven by our circadian timing system and that sleep (deprivation) has less of an influence on pain sensitivity than previously thought. Further research is required to identify the neural pathways linking circadian rhythms to pain perception. These findings suggest the effectiveness of pain relief could be optimized using circadian medicine, administering treatments based on the patient’s internal time.