Pain thresholds and suprathreshold pain after sleep restriction in migraine - A blinded crossover study

Abstract

Objective: There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls.

Methods: Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep.

Results: The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group.

Conclusion: This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.

Keywords: Pressure pain threshold; allodynia; headache; heat pain threshold; photophobia.

Figure 1.

Overview of the study’s timeline. All participants completed sleep diary and wore an actigraph. Only migraineurs completed headache diaries. Participants slept for 4 hours for two consecutive nights (sleep restriction condition) prior to one of the examination days, and slept habitually prior to the other. The order of sleep conditions was balanced between examination days and randomised before commencement of each participant’s study period. Randomisation was done in blocks and separately for controls and migraineurs to ensure that the order of sleep conditions was similar in both groups throughout the study. The interval between Baseline and Day 1, and Day 1 and Day 2, could vary between 3-10 days and 1-4 weeks, respectively, to ensure sufficient flexibility for participants. The lower limit of 1 week was chosen to minimise potential residual sleep deprivation effects in the case of sleep restriction prior to Day 1.

Figure 2.

Flow chart showing inclusion of migraineurs in the study.

Figure 3.

Box plot of the primary response variables: heat pain threshold (HPT) and heat pain tolerance threshold (HPTT) (above), pressure pain threshold (PPT) and pressure pain at VAS = 50/100 (PP5) (below) for each sleep condition and group. The box plot shows the 25th and 75th percentile as borders, and the median as a line. The whiskers show upper and lower adjacent values. Circles and diamonds show outliers. PP5 measurements from one test subject are omitted from this figure, as they were impractically large for depiction (HS: 256 N, SR: 415 N). Residual diagnostics were acceptable, and transformed values were normally distributed, so these values were not excluded from analyses. Using a 1 cm² probe, 10 N correspond to 100 kPa. Note that thermal thresholds use the same range for the y-axis, while pressure thresholds do not.

Figure 4.

Pressure pain threshold (PPT) (left) and heat pain threshold (HPT) (right) in a secondary analysis using a 48-hour cut-off for the preictal phase. Graphical display of estimated margins with 95% confidence intervals from a multilevel model, showing the effect of habitual versus restricted sleep (SR) in interictal migraineurs and controls. PPT tended to be lowered more by SR in migraineurs than in controls. For HPT, the point estimate was lower after SR in migraineurs, but the finding was not significant. P-values for all effects are shown in Table S2.

Figure 5.

Heat pain tolerance threshold (HPTT) in the primary analysis, using a 24-hour cut-off for the preictal phase. Graphical display of estimated margins with 95% confidence intervals from the main multilevel model, showing the effects of habitual and restricted sleep in interictal migraineurs and controls. HPTT tended to be lower in migraineurs for both sleep conditions. P-values for the simple effects are shown in Table 4.

Figure 6.

Heat pain threshold (HPT). Graphical display of estimated margins with 95% confidence intervals from a multilevel model, showing the effect of habitual vs. restricted sleep (SR) in migraineurs with mild/moderate compared with severe headache intensity during attacks. HPT was lower after SR compared to habitual sleep in the mild/moderate group. HPT was different between the groups for the SR condition.

Figure 7.

Pressure pain threshold (PPT). Graphical display of estimated margins with 95% confidence intervals from a multilevel model, showing the effect of habitual versus restricted sleep (SR) in migraineurs with mild/moderate compared with severe intensity of photophobia during migraine attacks. PPT was lower after SR in the group with severe photophobia, with a significant interaction between photophobia group and sleep condition. Using a 1 cm² probe, 10 N correspond to 100 kPa.