Individual Variation in Sleep Quality and Duration Is Related to Cerebral Mu Opioid Receptor Binding Potential during Tonic Laboratory Pain in Healthy Subjects

Abstract

Objective Although poor sleep is a consequence of pain, sleep disturbance reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual models of chronic pain implicate dysfunctional supraspinal pain processing mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work indicates that sleep disruption impairs psychophysical measures of descending pain modulation, but few studies have investigated whether insufficient sleep may be associated with alterations in endogenous opioid systems. This preliminary, exploratory investigation sought to examine the relationship between sleep and functioning of the cerebral mu opioid system during the experience of pain in healthy participants. Subjects and Design Twelve healthy volunteers participated in a 90-minute positron emission tomography imaging scan using [11C]Carfentanil, a mu opioid receptors agonist. During the session, pain responses to a 10% topical capsaicin cream were continuously rated on a 0–100 scale. Participants also completed the Pittsburgh Sleep Quality Index (PSQI). Results Poor sleep quality (PSQI) was positively and significantly associated with greater binding potential (BP) in regions within the frontal lobes. In addition, sleep duration was negatively associated with BP in these areas as well as the temporal lobe and anterior cingulate. Conclusions These findings suggest that poor sleep quality and short sleep duration are associated with endogenous opioid activity in these brain regions during the application of a noxious stimulus. Elucidating the role of the endogenous opioid system in mediating some of the associations between sleep and pain could significantly improve our understanding of the pathophysiology of chronic pain and might advance clinical practice by suggesting interventions that could buffer the adverse effects of poor sleep on pain.

Sleep, Pain Catastrophizing, and Central Sensitization in Knee Osteoarthritis Patients With and Without Insomnia

“…Several reports have found a relationship between catastrophizing and temporal summation of pain, a marker of CS(17;18). A number of published reports have documented the relationship between poor/disturbed sleep and hyperalgesia(7;20). In addition, one study by members of our group found that a significant proportion of variance in clinical pain severity and pain-related interference attributable to pain catastrophizing was actually mediated by sleep disturbance in a facial pain population(16).…”

“…In addition to the primary aims, we also explored the extent to which pain catastrophizing moderated the association of subjective sleep efficiency, which has well-documented associations with clinical and laboratory pain(20) as well as catastrophic thinking(14;21), and CS across subjects. The diary measure of sleep efficiency was chosen as it is widely used and well-validated in older adults(22) and represents individual’s perception of their own sleep.…”

Sleep Duration and Area-Level Deprivation in Twins

“…on SES, such as chronic pain 64 and psychological illness, 65 may also interfere with attempts to obtain adequate sleep. Detailed research that collects individual level, real-time data on noise exposure, activity levels, stress hormones, and sleep length and quality are needed to better define the opportunities for intervention to improve sleep health in those living in deprived areas.…”

Experimental sleep disruption attenuates morphine analgesia: findings from a randomized trial and implications for the opioid abuse epidemic

“…These and other pre-clinical studies have found that sleep loss alters molecular pathways in cerebral MOR activated anti-nociceptive circuits in the periaqueductal grey, hypothalamus, and mesolimbic structures, providing a neurobiological substrate supporting the current findings. In addition, a prior [ 11 C] Carfentanil Positron Emission Tomography (PET) study provides correlational support in humans, demonstrating that short sleep duration was associated with increased MOR availabilty during experimental pain (indicating down regulation of cerebral MOR or diminished release of endogenous opioid peptides) in brain structures associated with pain inhibiton (i.e., anterior cingulate gyrus and dorsolateral preforntal cortex) 31 .…”