Bernd Kundermann

Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers.

Objective: Sleep disturbances have been thought to augment pain. Sleep deprivation has been proven to produce hyperalgesic effects. It is still unclear whether these changes are truly specific to pain and not related to general changes in somatosensory functions. The aim of the present study was to evaluate the effect of total sleep deprivation on thermal pain thresholds (heat, cold) and pain complaints. Thermal detection thresholds (warmth, cold) were included as covariates to determine the contribution of somatosensory functions to changes in pain processing. Methods: Twenty healthy volunteers were randomly assigned either to two nights of total sleep deprivation or to two nights of undisturbed night sleep. Sleep deprivation nights were separated by two days with normal night sleep. Heat and cold pain thresholds as well as warmth and cold detection thresholds were measured by use of a peltier thermode in the evening before and the morning after each deprivation or control night. Pain complaints were examined by use of a questionnaire in parallel. Results: During treatment nights, sleep deprivation produced a significant overnight decrease in heat pain thresholds. Cold pain thresholds tended to decrease also during sleep deprivation, whereas the warmth and cold detection thresholds remained unaffected. Accordingly, no substantial contributions of the changes in thermal detection thresholds to the changes in thermal pain thresholds were determined by regression analyses. Pain complaints were not induced by sleep deprivation. Conclusions: The present findings suggest that sleep deprivation produces hyperalgesic changes that cannot be explained by nonspecific alterations in somatosensory functions. REM = rapid eye movement; SEM = standard error of the mean.

The effect of sleep deprivation on pain.

Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can counteract analgesic effects of pharmacological treatments involving opioidergic and serotoninergic mechanisms of action. The heterogeneity of the human data and the exclusive interest in rapid eye movement sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity. The significance of opioidergic and serotoninergic processes as mediating mechanisms of the hyperalgesic changes produced by sleep deprivation are discussed.

Effects of total sleep deprivation in major depression: overnight improvement of mood is accompanied by increased pain sensitivity and augmented pain complaints.

Objective: Major depressive disorder (MDD) is associated with more pain complaints and an altered pain perception. Studies regarding the longitudinal relationship between depressive symptoms and pain processing have rarely been performed and have produced inconsistent results. To clarify how short-term alleviation of depressive mood is linked to changes in pain processing, the effect of sleep deprivation (SD) on pain and somatosensory thresholds, pain complaints, and mood was investigated in MDD patients. Methods: Nineteen drug-free inpatients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, diagnosis of MDD were investigated for 3 weeks. All patients received cognitive-behavioral therapy and were randomized to obtain either additional SD therapy (six nights of total SD, separated by recovery sleep) or no SD therapy (control group). Heat/cold pain thresholds, warmth/cold thresholds, measures of current pain complaints, and mood were assessed the evening before and the morning after SD as well as before and after a normal night sleep in the control group. Long-term changes of depressive symptomatology were assessed by weekly mood ratings. Results: Both treatment groups improved markedly in mood over the 3-week treatment period. SD regularly induced a moderate but statistically nonsignificant overnight improvement of mood, which was abolished by recovery sleep. Compared with the control condition, SD significantly decreased heat pain thresholds and nearly significantly cold pain thresholds; SD significantly augmented pain complaints the next morning. No such effects were observed for somatosensory thresholds. Conclusions: SD induced differential short-term effects on mood and pain, with the patients being less depressed but more pain vulnerable. MDD = major depressive disorder; SD = sleep deprivation; CDT = cold detection threshold; WDT = warmth detection threshold; CPT = cold pain threshold; HPT = heat pain threshold; BDI = Beck Depression Inventory; HDRS = Hamilton Depression Rating Scale; ANOVA = analysis of variance; GG = Greenhouse-Geisser; D-S = Depression Scale; Bf-S = Scale of Well-Being.

Pain sensitivity in major depression and its relationship to central serotoninergic function as reflected by the neuroendocrine response to clomipramine

Several studies reported a decreased pain sensitivity in patients with depression, but the underlying neurobiological mechanisms of this phenomenon are unclear. While there is extensive evidence that the serotoninergic system plays a key role in pain modulation, especially in pain inhibitory mechanisms via descending pathways, as well as in the pathophysiology of depression, no study so far has examined its potential relevance in mediating the alteration of pain processing. The present study addresses the question of whether indices of serotoninergic dysfunction, as investigated by a neuroendrocine challenge paradigm, are related to pain sensitivity. Nineteen drug-free inpatients with unipolar major depression underwent a neuroendocrine challenge test by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg). Heat/cold pain thresholds, warmth/cold detection thresholds, measures of current pain complaints and mood were assessed the day before and three day after challenge procedure. When patients were classified in subgroups based on a median split of their cortisol response values, the low-responsive group showed significantly elevated heat pain thresholds and nearly significantly elevated cold pain thresholds compared to the high-responsive group. No such group differences were found with regard to somatosensory thresholds, measures of pain complaints and mood. Subgrouping on the basis of prolactin responsiveness did not reveal significant differences in any parameter. In summary, a decreased pain sensitivity was demonstrated in patients characterized by a reduced neuroendocrine responsiveness to clomipramine, suggesting an involvement of serotoninergic dysfunction underlying altered pain perception in depression.

Chronotypes in patients with nonseasonal depressive disorder: Distribution, stability and association with clinical variables.

The individual’s chronotype is regarded as rather stable trait with substantial heritability and normal distribution of the “morningness–eveningness” dimension in the general population. Eveningness has been related to the risk of developing affective, particularly depressive, disorders. However, age and other sociobiological factors may influence chronotypes. The present study investigated the distribution, stability, and clinical correlates of chronotype and morningness–eveningness in hospitalized patients with affective disorder. Chronotype was assessed with the morningness–eveningness questionnaire (MEQ) in 93 patients with nonseasonal depressive syndrome (85% major depression; 15% depressive adjustment disorder) after admission, and in 19 patients again before discharge. Distribution, stability and correlations of MEQ scores with clinical variables were calculated. Additionally, a literature analysis of chronotype distributions in samples of nondepressed persons and patients with nonseasonal depression was carried out. MEQ scores (mean 49 ± 11, range 23–75, higher scores indicate morningness) in 93 acutely depressed inpatients (age 41 ± 14 years, range 18–75 years; 63% women; hospitalization 48 ± 22 days; BDI-II 32 ± 11) were normally distributed (Shapiro–Wilk test; W = 0.993, p = 0.920) with 59.1% intermediate types, 19.4% evening types, and 21.5% morning types. MEQ change scores from admission to discharge were nonsignificant (−1.3 ± 5.0; paired t-test, t18 = −1.09; p = 0.29) despite significantly improved depression scores (−19.4 ± 7.6; paired t-test, t18 = 11.2, p < 0.001). Age (r = 0.24), and depression scores (r = −0.21) correlated significantly (p < 0.05) with MEQ scores; associations with sex and hospitalization duration were nonsignificant. The present study and literature findings revealed that the frequency of evening types is not clearly elevated in depression, but morning types are less frequent compared to healthy samples (p < 0.001). Morningness–eveningness scores were normally distributed and stable in depressive inpatients. In line with previous findings, but contrary to theoretical assumptions, evening types were not overrepresented in depressed patients. Additionally, relatively less morning types and more intermediate types were found in depressed patients. Future studies should focus on transitions from morning to intermediate types as a tentative risk or correlate of emerging depression.

Eveningness and poor sleep quality independently contribute to self-reported depression severity in psychiatric inpatients with affective disorder

Abstract Background Chronotype and insomnia have been related to the development and to an unfavourable course of depression. However, the mutual relationship of both risk factors is as yet unclear, especially in acute, clinically manifest depressive disorders. Aims The present study was carried out to elucidate the separate direct and indirect influence of chronotype and poor sleep quality on depression severity in patients hospitalized for depression. Methods Depression severity (BDI-II), chronotype (Morningness–Eveningness Questionnaire), and subjective sleep quality (Pittsburgh Sleep Quality Index total score) were assessed concurrently in inpatients with a depressive syndrome and insomnia during routine treatment. Correlations, multiple regression and bootstrapping methods for testing mediation models were applied to assess the independent direct and indirect effects of chronotype and sleep quality on depression severity, after adjusting for effects of age and gender. Results Data from 57 consecutively admitted patients (88% with major depression) were analyzed (68% women, mean age 41 ± 13 years). Significant correlations between morningness–eveningness (p <0.05) or sleep quality (p <0.01) and depression severity were found; in a multiple regression model comprising chronotype, sleep quality, age and gender, only chronotype (p <0.05) and sleep disturbances (p <0.01) remained as independent significant concurrent predictors of depression severity (R2 = 0.184, p <0.01). Two mediation models revealed no significant results. Conclusions Eveningness and poor subjective sleep quality were independently and directly associated with higher depression severity in inpatients with depressive syndromes. Chronotype and sleep quality should be taken into account not only in risk assessment and prevention but also in hospitalized patients to develop and improve treatment options.

The Effects of Oral Contraceptives on Detection and Pain Thresholds As Well As Headache Intensity During Menstrual Cycle in Migraine

(Headache 2011;51:92‐104)

Endogenous pain inhibition during menstrual cycle in migraine

Migraine is a common headache disorder that can vary menstrually in women and has been linked to an impairment of endogenous pain inhibitory systems. One of these endogenous pain inhibitory systems, namely conditioned pain modulation (CPM; formerly diffuse noxious inhibitory controls‐like), has been shown to be affected by the menstrual cycle. The aim of this study was to examine CPM over the menstrual cycle in migraineurs and healthy controls.

Mid-term effects of serial sleep deprivation therapy implemented in cognitive-behavioral treatment on the neuroendocrine response to clomipramine in patients with major depression

While data dealing with neurobiological effects of sleep deprivation (SD) are mainly restricted to the acute effects of a single night, only few studies have investigated mid-term effects after repeated SD. We therefore examined the clinical and hormonal characteristics of depressive patients before and after serial SD to determine potential sustained effects, focusing especially on serotoninergic functions. One tool to investigate serotoninergic dysfunction in depression is the use of serotoninergic agents to stimulate hormonal secretion, which is assumed to normalize during a clinically effective therapy. Eighteen drug-free inpatients with unipolar major depression received cognitive-behavioral treatment for three weeks and - according to a randomized control design - additional SD therapy (six nights of total SD within three weeks, separated by nights of recovery sleep) or no SD therapy (control group). Serotoninergic function was assessed by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg) before and after the treatment period. The post-treatment challenge test was performed three days after the last SD night. Apart from of a transient overnight improvement of mood induced by SD, both groups showed a comparable clinical course during the three-week treatment period. Compared to the control group, the SD-treated patients exhibited significantly decreased pre-stimulation cortisol levels and significantly increased cortisol responses to clomipramine, whereas no treatment effects were observed for prolactin. In conclusion, our findings suggest that the mid-term effects of serial SD therapy lead to a normalization of serotoninergic dysfunction, although an obvious impact on clinical symptoms was not detected.

[Sleep deprivation and pain: a review of the newest literature].

It has now been established that sleep deprivation or fragmentation causes hyperalgesia which cannot be explained by a general change in somatosensory perception. However, it has not yet been clarified which of the sleep stages are most relevant for this effect. The seemingly paradoxical effects of sleep deprivation on pain-evoked brain potentials on the one hand and the subjective pain report on the other hand suggest complex changes in gating mechanisms. As the effects on pain and affect can be dissociated a common mechanism of action seems unlikely. Data from animal studies suggest that hyperalgesia due to sleep deprivation might be particularly strong under preexisting neuropathic conditions. Together with results from animal research the finding that endogenous pain modulation (CPM) is impaired by sleep deprivation suggests that the serotoninergic system mediates the effect of sleep deprivation on pain perception. However, other neurotransmitters and neuromodulators still have to be considered. The clinically relevant question arises why sleep deprivation induces hyperalgesia more easily in certain individuals than in others and why this effect then has a longer duration?ZusammenfassungEs ist mittlerweile unstrittig, dass Schlafentzug bzw. -fragmentierung zu Hyperalgesien führt, die sich nicht als allgemeine Veränderung der Somatosensorik erklären lassen. Welche Schlafphasen für die Deprivationswirkung am relevantesten sind, ist nicht ausreichend geklärt. Teilweise paradox anmutende Befunde zur Deprivationswirkung auf schmerzevozierte Hirnpotenziale einerseits und subjektives Schmerzerleben andererseits lassen komplizierte Veränderungen von Gating-Mechanismen vermuten. Da die Wirkungen auf Affekt und Schmerz dissoziieren können, ist ein gemeinsamer Wirkungsmechanismus unwahrscheinlich. Daten aus Tierstudien lassen vermuten, dass schlafentzugsbedingte Hyperalgesien bei bestehenden Neuropathien besonders ausgeprägt sind. Einige tierexperimentelle Ergebnisse sowie der Befund, dass Schlafdeprivation die endogene Schmerzhemmung [“conditioned pain modulation“ (CPM)] stört, führten zu der Annahme, dass das serotoninerge System die Wirkung von Schlafentzug auf das Schmerzsystem vermittelt. Andere Neurotransmitter und -modulatoren müssen aber weiterhin berücksichtigt werden. Klinisch gilt es zu klären, warum bei bestimmten Personen schlafentzugsbedingte Hyperalgesien besonders leicht auftreten und länger persistieren.AbstractIt has now been established that sleep deprivation or fragmentation causes hyperalgesia which cannot be explained by a general change in somatosensory perception. However, it has not yet been clarified which of the sleep stages are most relevant for this effect. The seemingly paradoxical effects of sleep deprivation on pain-evoked brain potentials on the one hand and the subjective pain report on the other hand suggest complex changes in gating mechanisms. As the effects on pain and affect can be dissociated a common mechanism of action seems unlikely. Data from animal studies suggest that hyperalgesia due to sleep deprivation might be particularly strong under preexisting neuropathic conditions. Together with results from animal research the finding that endogenous pain modulation (CPM) is impaired by sleep deprivation suggests that the serotoninergic system mediates the effect of sleep deprivation on pain perception. However, other neurotransmitters and neuromodulators still have to be considered. The clinically relevant question arises why sleep deprivation induces hyperalgesia more easily in certain individuals than in others and why this effect then has a longer duration?