Differential effect of codeine on thermal nociceptive sensitivity in sleepy versus nonsleepy healthy subjects.

Abstract

Basal sleepiness-alertness modulates drug effects. Sleepiness produced by sleep restriction leads to increased nociceptive sensitivity, suggesting opioid analgesia may also be modulated by sleepiness-alertness. This study compared thermal nociceptive sensitivity in sleepy versus nonsleepy participants after codeine or placebo. Twelve healthy normal adults, 18 to 35 years of age, had an 8-hr nocturnal polysomnogram (NPSG) followed by a Multiple Sleep Latency Test (MSLT; Carskadon and Dement, 1987). All had sleep efficiencies > 80% on their NPSG; 6 had average MSLT >or= 8 min (nonsleepy group) and 6 had latencies < 8 min (sleepy group). Participants were assessed following 8-hr time-in-bed with standard MSLT, and nociceptive assessments (using a radiant heat stimulation method) were conducted the following day with codeine 30 mg b.i.d. (0900 and 1300) or placebo b.i.d. Finger withdrawal latency (FWL) in seconds was measured to 5 different heat intensities randomly presented to the index finger pad of each hand. Mean +/- 1 SD MSLT values in the sleepy group were 4.72 +/- 1.83 min and 13.04 +/- 4.90 min in the nonsleepy group. As hypothesized, increased FWL (decreased nociception) was observed with lower heat intensities, codeine, and in the nonsleepy group. More important, there was a Group x Drug interaction with codeine increasing FWL in the nonsleepy, but not the sleepy, group. These data show the analgesic effects of codeine are diminished in sleepy versus nonsleepy individuals. They suggest clinical differences in response to analgesics are partly explained by basal state of sleepiness-alertness.

The Association of Sleep and Pain: An Update and a Path Forward

“…Animal studies have found that sleep deprivation alters μ and δ opioid receptor function in mesolimbic circuits 31 , diminishes basal endogenous opioid levels 86 and down regulates central opioid receptors 32 . A recent study with humans supports these preclinical findings by demonstrating that diminished codeine analgesia is correlated with daytime sleepiness 110 . Sleep, however, was not assessed.…”

The effect of sleep deprivation on pain perception in healthy subjects: a meta-analysis

“…A medium effect (SMD=0.62) was found for the between group analysis and a large effect (SMD=1. 49) was found for the within group analysis. Sleep deprivation increases self-reported pain and affects evoked pain responses obtained through somatosensory testing protocols (e.g.…”

“…We identified 34 potential eligible studies by screening the titles and abstracts. After full-text analyses, we excluded 21 studies for the following reasons: no primary research [40][41][42], no experimental design [43], no sleep deprivation [44][45][46][47][48][49], no primary pain outcome [50,51], only non-healthy participants [52] and no opportunity to calculate effect size [2,7,9,19,[53][54][55][56]. From the remaining 13 studies, eight studies were randomized controlled trials and five studies were uncontrolled.…”

Napping Reverses Increased Pain Sensitivity Due to Sleep Restriction

“…Indeed, pain nociception, as assessed by the time to finger withdrawal following exposure to a radiant heat stimulus, has been shown to be specifically associated with an increase in alertness in healthy subjects [10, 36]. One group compared pain nociception before and after a night of extended sleep, in sleepy individuals [10].…”

“…One group compared pain nociception before and after a night of extended sleep, in sleepy individuals [10]. Another group compared a non-sleepy group of healthy subjects (as defined by a latency > 8 min at the multiple sleep latency test) to a group of sleepier subjects (as defined by a latency < 8 min at the multiple sleep latency test) [36]. Increases in objective sleepiness were found to be associated with decreases in pain threshold.…”