Sleep & Chronic Pain/Depression

Transcription

1 Sleep & Chronic Pain/Depression BC Professor, University of Massachusetts Lowell As promised, these are the slides from my presentation at CPI which were not included in the distributed slides. BC 1

2 Sleep, Pain and Depression: Exploring the Relationships A Couple Lenses on Sleep, Pain and Depression Changes in sleep architecture/changes in sleep homeostasis Changes in sleep architecture, particularly with increases in arousal and lower sleep efficiency Changes in neurochemical regulation/changes in circadian functions Sleep is under powerful humoral control BC 2

3 Sleep Architecture Sleep Architecture and Pain Pain creates fragmentation in sleep architecture evidenced by more arousal in the EEG. Reduction in sleep efficiency is common. Sleep efficiency = time asleep time in bed. Poor sleep efficiency is the culprit in enhanced pain perception p (even in the absence of depression.) Haack & Mullington, 2005; Kundermann B et al. (2008). Psychosomatic Medicine, 70 (1), pp BC 3

4 Sleep Architecture and Depression Reduced sleep efficiency (and the imposed sleep deprivation) are directly related to onset and course of depression as well as risk for relapse. Subjective and objective measures parallel each other. The relationship is bidirectional, e.g., sleep impacts mood and vice versa. The sleep/depression relationship powerfully impacts pain perception, p,given the shared relationship with sleep efficiency. Ohayon, M. Journal of Psychiatric Research 43 (2009) Sleep Architecture in Comorbid Depression & Pain Sometimes indistinguishable. In fibromyalgia, the sleep architecture cannot be distinguished from that of major depression: Reduced sleep efficiency REM occurs too early in the sleep period Reduced deep restorative sleep, NREM stages 3 and 4. BC 4

5 Sleep Loss in Pain & Depression 4 hours of sleep loss and specific REM sleep loss are hyperalgesic the following day. Pharmacologic treatments and clinical conditions that reduce sleep and REM sleep time may increase pain. Sleep deprivation is negatively associated with course/outcome of depression. Hyde M; Blaisdell B et al. Sleep loss and REM sleep loss are hyperalgesic. SLEEP 2006 Neurochemical Regulation of Sleep BC 5

6 Sleep/Wake Neurotransmitters and Modulators Wake Norepinephrine p Serotonin Acetylcholine Histamine Orexin/hypocretin Sleep Adenosine (caffeine is an adenosine antagonist) GABA Galanin Serotonin/melatonin Depression/Sleep Neurotransmitters and Modulators Norepinephrine Modulates arousal regulation; wakepromoting (as seen in MOA for drugs like modafinil); critical to attention/mood. Serotonin Critical to activation and alertness; tight relationship with melatonin in regulating sleep and wake via the circadian system. Mood/anxiety regulation. Dopamine Promotes wakefulness (MOA with stimulants). Mood, focus, attention regulation. BC 6

7 Pain Neurotransmitters and Modulators Substance P, glutamate, bradykinin (pain initiators); substance P increases histamine in pain. Histamine is a powerful wakefulness chemical. Proinflammatory cytokines are central to pain but are active in depression, influencing the HPA Pain Neurotransmitters and Modulators Serotonin, endorphins, enkephlins (pain inhibitors) Norepinephrine Inhibitory influence in pain GABA Inhibitory influence in pain Acetylcholine Inhibitory influence in pain BC 7

8 Neurochemistry: The Role of Serotonin in Pain Serotonin sub receptor type 5HT 1a plays an important role in pain regulation and pain sensitivity. Sleep deprivation enhances pain sensitivity, probably via a 5HT 1a mechanism Opiodergic pain inhibition circuits in the brainstem are under serotonergic and noradrenergic control. Ohayon, 2009; Smith, 2010 Just a Word on Sleep & Immunity Sleep deprivation/lack of sleep is associated with: Reduction in T cells Reduction in natural killer cells Increase in proinflammatory cytokines SNRI s impact on pain and immunity is related to SNRI s impact on pain and immunity is related to the drug s impact on the inhibition of the inflammatory TNF. BC 8

9 Sleep Architecture and Pain Pain creates fragmentation in sleep architecture evidenced by more arousal in the EEG. Reduction in sleep efficiency is common. Sleep efficiency = time asleep time in bed. Poor sleep efficiency is the culprit in enhanced pain perception p (even in the absence of depression.) Haack & Mullington, 2005; Kundermann B et al. (2008). Psychosomatic Medicine, 70 (1), pp Sleep Architecture and Depression Reduced sleep efficiency (and the imposed sleep deprivation) are directly related to onset and course of depression as well as risk for relapse. Subjective and objective measures parallel each other. The relationship is bidirectional, e.g., sleep impacts mood and vice versa. The sleep/depression relationship powerfully impacts pain perception, given the shared relationship with sleep efficiency. Ohayon, M. Journal of Psychiatric Research 43 (2009) BC 9

10 Sleep Architecture in Comorbid Depression & Pain Sometimes indistinguishable. In fibromyalgia, i the sleep architecture cannot be distinguished from that of major depression: Reduced sleep efficiency REM occurs too early in the sleep period Reduced deep restorative sleep, NREM stages 3 and 4. Sleep Loss in Pain & Depression 4 hours of sleep loss and specific REM sleep loss are hyperalgesic the following day. Pharmacologic treatments and clinical conditions that reduce sleep and REM sleep time may increase pain. Sleep deprivation is negatively associated with course/outcome of depression. Hyde M; Blaisdell B et al. Sleep loss and REM sleep loss are hyperalgesic. SLEEP 2006 BC 10

11 Neurochemical Regulation of Sleep Sleep/Wake Neurotransmitters and Modulators Wake Norepinephrine p Serotonin Acetylcholine Histamine Orexin/hypocretin Sleep Adenosine (caffeine is an adenosine antagonist) GABA Galanin Serotonin/melatonin BC 11

12 Pain Neurotransmitters and Modulators Substance P, glutamate, bradykinin (pain initiators); substance P increases histamine in pain. Histamine is a powerful wakefulness chemical. Proinflammatory cytokines are central to pain but are active in depression, influencing the HPA Pain Neurotransmitters and Modulators Serotonin, endorphins, enkephlins (pain inhibitors) Norepinephrine Inhibitory influence in pain GABA Inhibitory influence in pain Acetylcholine Inhibitory influence in pain BC 12

13 Neurochemistry: The Role of Serotonin in Pain Serotonin sub receptor type 5HT 1a plays an important role in pain regulation and pain sensitivity. Sleep deprivation enhances pain sensitivity, probably via a 5HT 1a mechanism Opiodergic pain inhibition circuits in the brainstem are under serotonergic and noradrenergic control. Ohayon, 2009; Smith, 2010 Neurochemistry: The Role of Serotonin in Depression Alterations in 5HT1a receptor levels are noted in depression and in suicide. Shortened sleep is associated with higher risk of suicidal ideation and suicide attempts. Desensitization of the 5HT1a autoreceptor is believed to be implicated in the 2 3 week lag with antidepressant medication onset. Goodwin RD & Marusic A, SLEEP 2008;31(8): BC 13

14 Just a Word on Sleep & Immunity Sleep deprivation/lack of sleep is associated with: Reduction in T cells Reduction in natural killer cells Increase in proinflammatory cytokines SNRI s impact on pain and immunity is related to the drug s impact on the inhibition of the inflammatory TNF. Additional Options for Insomnia BC 14

15 Atypical Antipsychotics for Insomnia Quetiapine (Seroquel), olanzapine (Zyprexa), risperidone (Risperdal) Advantages Mildly to moderately sedating Useful for comorbid psychiatric disorders Anxiolytic Minimal abuse potential Disadvantages Limited effectiveness Residual daytime sedation Multiple potential acute and chronic adverse effects Atypical Antipsychotics for Insomnia If you are prescribing second generation antipsychotic medications for sleep, are you following the practice guidelines for metabolic monitoring? Just because the use of the drug is not for the treatment of psychosis or a major mod disorder, the metabolic risks do not change! BC 15

16 Resources National Sleep Foundation Sleep Education Redeker NS & Phillips McEnany G. Sleep Disorders & Sleep Promotion in Nursing Practice. New York: Springer Publications, BC 16