Sleep, Pain and Drugs
Paul Reading
Department of Neurology
The James Cook
University Hospital
1. defining sleep and the sleep drive
2. how much sleep do we need?
importance of quantity and quality
3. the effects of s...
Everyone and every animal
needs to sleep!
If sleep doesn’t serve some vital function it is
the biggest mistake evolution e...
1 2 3 4 5 6 7
Time (hours through night)
WAKING
REM
Sleep
I
II
III
IV
Typical Hypnogram
of Young Adult
REMREM REM REM
EEG (central)
EEG (occipital)
OCULOGRAM
CHIN EMG
PHYSIOLOGICAL
CORRELATES
OF SLEEP
STAGES
50%
15%
10%
20%
~5% total sleep
 Borbély’s two factor hypothesis (1982) :
the need for sleep dependent on :
• homeostatic factors
(process S)
• “hour gla...
 We still don’t really know!
 There is clear inter-individual variation
e.g. Einstein v Thatcher and Napoleon
but whole ...
British Medical Journal :
editorial – Sept 29th
“The subject of sleeplessness is once more
under public discussion. The hu...
8 hrs/night
0 14 140
6 hrs/night
4 hrs/night
0 hrs/night
Data suggest increasing signs of sleepiness
with regular 6 hours ...
 animals will die in about 2 weeks
• both REM and non-REM needed
• mechanism of death?
Acute Sleep Deprivation
in animals
The Effects of Acute Sleep Deprivation
in humans
Sleepy!
The risks of sleepiness
Selby Rail Crash
06:12h: car drifts off road, down embankment onto railway.
Hit by passenger train...
 in late 1960’s landmark studies on prolonged SD
students paid on a sliding pay scale (up to 205 hours)
• day 3 - signifi...
The Effects of Acute Sleep Deprivation
 Involuntary “micro sleeps” occur
 Reaction times slower
 Attention becomes unst...
Dawson & Reid (Nature 1997)
Effect of Sleep Deprivation on Psychomotor Performance
Compared With Blood Alcohol Concentrati...
The Effects of Acute Sleep Deprivation
Brain imaging
 after 24hr SD
prefrontal
cortex (PFC)
underactive
 during cognitiv...
 impaired sense of humour (Sleep 2006)
The Effects of Acute Sleep Deprivation
Headline 1:
Vet investigates failed
panda m...
 all drugs improved PVT scores
 placebo performance 1 SD below expected
 modafinil improves visual joke appreciation
du...
 greater risk taking and reduced learning about losses (Sleep 2007)
The Effects of Acute Sleep Deprivation
• If 24h SD, o...
The Effects of Acute Sleep Deprivation
• After 24h SD, “angry” and “happy” emotions less recognised
recovery after sleep p...
The Adverse “Emotional” Effects of
Sleep Deprivation
 Sleep loss in medical residents amplified negative emotional
conseq...
Does chronic severe sleep deprivation
and/or pain shrink (age) the brain?
gray matter changes in
brains of severe OSA in
m...
(Possible) Systemic Effects of
Chronic (partial) Sleep Deprivation
 Sleep loss may affect metabolism
• resistance to insu...
Chronic Sleep Deprivation
don’t forget children!
 growth hormone deficiency?
hGH spurt with
first SWS period
The Causes of Excessive Sleepiness
Primary Sleep Disorders
with sleep-wake dysregulation
• Narcolepsy
• Idiopathic hyperso...
“Secondary” Insomnia
Medical causes
• Obstructive sleep apnoea
• Asthma
• Oesophageal reflux
• Prostatism / nocturia
• Pai...
Pain and Sleep
Genetics
Pain and Sleep
a bi-directional relationship
Pain ↑ → Sleep ↓
5-HT ↓ → Pain ↑ and Sleep ↓
Sleep ↓ → Pain ↑
 Clinical obse...
 Sleep deprivation (REM?) decreases pain thresholds
poor sleep quality also affects QOL and ability to cope
Roehrs et al ...
 commonly used drugs to treat nocturnal pain may
facilitate sleep onset and increase duration
but not improve its quality...
 Sleep architecture “improved” by Pregabalin
Pregabalin compared to placebo and BZ over 3 nights in volunteers
Hindmarch ...
 RCT (n=370)
• twice daily PGB
• improved pain
scores
• improved sleep
interference
(sleep diaries)
Van van Seventer et a...
 Gabapentin
 Tiagabine (Gabatril)
 Xyrem (sodium oxybate, GHB)
 Melatonin?
 Cannabis?
Other drugs that “improve” or i...
Fibromyalgia
 Fibromyalgia common (3%?)
 Defined by pain symptoms but sleep abnormal
poor sleep efficiency, reduced stag...
Fibromyalgia
 Very recent randomised controlled trial
Moldofsky J Rheum 2010
 195 FM patients randomised to
oxybate (4.5...
anxiety
poor
sleep
pain
Pain should not be
treated in isolation
DON’T FORGET SLEEP!
quantity and quality...
Sleep, pain and drugs
Sleep, pain and drugs
Upcoming SlideShare
Loading in …5
×

Sleep, pain and drugs

2,270 views

Published on

Lecture given to the West of Scotland Pain Group on Wednesday 24th November 2010 in the Ebenezer Duncan Centre, Victoria Infirmary, Glasgow by Dr Paul Reading, Consultant Neurologist.
In this talk, Dr Reading describes the importance of good quality sleep and how pain and sleep interact.
www.wspg.org.uk

Published in: Health & Medicine, Business
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,270
On SlideShare
0
From Embeds
0
Number of Embeds
840
Actions
Shares
0
Downloads
0
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide

Sleep, pain and drugs

  1. 1. Sleep, Pain and Drugs Paul Reading Department of Neurology The James Cook University Hospital
  2. 2. 1. defining sleep and the sleep drive 2. how much sleep do we need? importance of quantity and quality 3. the effects of sleep deprivation 4. the causes of excessive sleepiness 5. the relation between pain and sleep 6. effects of drugs for pain on sleep quality
  3. 3. Everyone and every animal needs to sleep! If sleep doesn’t serve some vital function it is the biggest mistake evolution ever made. Alan Rechtschaffen Sleep is of the brain, by the brain and for the brain William Dement The best bridge for repair between despair and hope is a good night’s sleep Joseph E Crossman
  4. 4. 1 2 3 4 5 6 7 Time (hours through night) WAKING REM Sleep I II III IV Typical Hypnogram of Young Adult REMREM REM REM
  5. 5. EEG (central) EEG (occipital) OCULOGRAM CHIN EMG PHYSIOLOGICAL CORRELATES OF SLEEP STAGES 50% 15% 10% 20% ~5% total sleep
  6. 6.  Borbély’s two factor hypothesis (1982) : the need for sleep dependent on : • homeostatic factors (process S) • “hour glass” • circadian factors (process C) • nadirs of alertness at ~ 4 am & ~ 3 pm The Triggers for Sleep SKIN MITOSIS
  7. 7.  We still don’t really know!  There is clear inter-individual variation e.g. Einstein v Thatcher and Napoleon but whole populations fairly homogenous : ~ 7 hrs of quality sleep needed for most  In Western society we [probably] sleep less than 90 years ago (young adults 6.8 v 8.2h)  The idea of a chronic “sleep debt” (that must be repaid) has become a widespread concept … How much Sleep do we Need?
  8. 8. British Medical Journal : editorial – Sept 29th “The subject of sleeplessness is once more under public discussion. The hurry and excitement of modern life is held to be responsible for much of the insomnia of which we hear; and most of the articles and letters are full of good advice to live more quietly and of platitudes concerning the harmfulness of rush and worry. The pity of it is that so many people are unable to follow this good advice and are obliged to lead a life of anxiety and high tension.” 1894
  9. 9. 8 hrs/night 0 14 140 6 hrs/night 4 hrs/night 0 hrs/night Data suggest increasing signs of sleepiness with regular 6 hours of nocturnal sleep but subjective sleepiness ≠ objective sleepiness Van Dongen et al Sleep 2002 PVT = psychomotor vigilance test How much Sleep does the Brain Need? 0 14 0 14
  10. 10.  animals will die in about 2 weeks • both REM and non-REM needed • mechanism of death? Acute Sleep Deprivation in animals
  11. 11. The Effects of Acute Sleep Deprivation in humans Sleepy!
  12. 12. The risks of sleepiness Selby Rail Crash 06:12h: car drifts off road, down embankment onto railway. Hit by passenger train - derailed, then hit by goods train 100 fatal & serious injuries
  13. 13.  in late 1960’s landmark studies on prolonged SD students paid on a sliding pay scale (up to 205 hours) • day 3 - significant concentration problems, visual symptoms also prominent • day 5 - intermittent confusion, numerous lapses • day 7 - hallucinations / delusions, psychomotor retardation (“dementia”)  no consistent biochemical abnormalities (cortisol higher)  no long lasting psychological / cognitive sequelae Acute Sleep Deprivation in humans
  14. 14. The Effects of Acute Sleep Deprivation  Involuntary “micro sleeps” occur  Reaction times slower  Attention becomes unstable • vigilance poor, lapses increase • short term memory suffers • unable to sustain performance • note effects on driving  Problem solving and judgement deteriorate • frontal lobe function particularly affected  Pain threshold reduced?
  15. 15. Dawson & Reid (Nature 1997) Effect of Sleep Deprivation on Psychomotor Performance Compared With Blood Alcohol Concentration
  16. 16. The Effects of Acute Sleep Deprivation Brain imaging  after 24hr SD prefrontal cortex (PFC) underactive  during cognitive tasks PFC and thalamus appear overactive similar to old age brain has to work “harder”?
  17. 17.  impaired sense of humour (Sleep 2006) The Effects of Acute Sleep Deprivation Headline 1: Vet investigates failed panda mating Headline 2: Panda mating fails: vet takes over
  18. 18.  all drugs improved PVT scores  placebo performance 1 SD below expected  modafinil improves visual joke appreciation due to improved frontal lobe function? Results
  19. 19.  greater risk taking and reduced learning about losses (Sleep 2007) The Effects of Acute Sleep Deprivation • If 24h SD, overactivation in nucleus accumbens when taking a risky gamble • higher expectation of reward? • If 24h SD, under-activation of orbitofrontal cortex following a loss • reduced learning about losses?
  20. 20. The Effects of Acute Sleep Deprivation • After 24h SD, “angry” and “happy” emotions less recognised recovery after sleep period
  21. 21. The Adverse “Emotional” Effects of Sleep Deprivation  Sleep loss in medical residents amplified negative emotional consequences of disruptive daytime experiences while positive benefits of rewarding activities were blunted (Zohar 2005)  In test of emotional memory, f-MR scans show limbic areas overactive to negative stimuli > 1 night SD (Yoo et al 2007)  “hyper-limbic state”  due to loss of functional connectivity with PFC? note similarities to depression i.e. over-reactive to negative events
  22. 22. Does chronic severe sleep deprivation and/or pain shrink (age) the brain? gray matter changes in brains of severe OSA in middle-age men Eun Yeon Joo et al Sleep 2010 gray matter changes in brains of sufferers of chronic back pain and fibromyalgia Apkarian et al J Neurosci 2004 Kuchinad et al J Neurosci 2007
  23. 23. (Possible) Systemic Effects of Chronic (partial) Sleep Deprivation  Sleep loss may affect metabolism • resistance to insulin, pre-diabetic state due to increased sympathetic activity / cortisol? especially in OSA + metabolic syndrome • hunger signals increased resistance to leptin, the “satiety hormone”  Sleep loss and inflammatory responses • altered immunity e.g. less effective vaccinations, increased cancer? (note Danish ruling) • inflammatory markers in blood increased (e.g. CRP) blood “stickier”, vascular complications
  24. 24. Chronic Sleep Deprivation don’t forget children!  growth hormone deficiency? hGH spurt with first SWS period
  25. 25. The Causes of Excessive Sleepiness Primary Sleep Disorders with sleep-wake dysregulation • Narcolepsy • Idiopathic hypersomnolence Sleepiness Secondary to a Chronic Disorder • Obstructive Sleep apnoea/hypopnoea syndrome • Restless legs syndrome • Parkinson’s disease • Depression • Myotonic dystrophy • Multiple sclerosis Circadian Misalignment • Shift work sleep disorder • Delayed sleep phase syndrome In real life? (voluntary) sleep restriction the environment pain other medical conditions 5% of population?
  26. 26. “Secondary” Insomnia Medical causes • Obstructive sleep apnoea • Asthma • Oesophageal reflux • Prostatism / nocturia • Pain syndromes diabetic neuropathy, fibromyalgia Neurological causes • Restless legs syndrome • Parkinson’s disease • Dementia • Morvan’s syndrome • Fatal familial insomnia Psychiatric causes • Medication related (stimulating anti- depressants) • Withdrawal-related • Anxiety disorders • Mood disorders “sleep toxins”
  27. 27. Pain and Sleep Genetics
  28. 28. Pain and Sleep a bi-directional relationship Pain ↑ → Sleep ↓ 5-HT ↓ → Pain ↑ and Sleep ↓ Sleep ↓ → Pain ↑  Clinical observations in burns patients (Raymond et al Pain 2001) subjective sleep quality predicts pain scores subsequent day but pain intensity during day does not predict sleep quality  Sleep deprivation in animals (REM) lowers pain threshold and reduces opiate efficacy pressure pain and heat tolerance affected, not general sensation
  29. 29.  Sleep deprivation (REM?) decreases pain thresholds poor sleep quality also affects QOL and ability to cope Roehrs et al Sleep 2006 Pain and Sleep 0 hrs8 hrs 4 hrs 8 hrs NRem Rem 0 hrs
  30. 30.  commonly used drugs to treat nocturnal pain may facilitate sleep onset and increase duration but not improve its quality :  Opiates REM ↓↓ SWS ↓↓ arousals ↑↑↑  AED’s REM ↓ SWS ↑  Anti-dep REM ↓(↓) SWS ↓↔ sleep maintenance ↓↔  BZ’s / alc REM ↓ SWS ↓ sleep maintenance ↑ Pain, Drugs and Sleep
  31. 31.  Sleep architecture “improved” by Pregabalin Pregabalin compared to placebo and BZ over 3 nights in volunteers Hindmarch et al Sleep 2005 after pregabalin, control subjects have: 1. increased SWS (absolute and proportional values) 2. reduced overall sleep latency and REM latency 3. sleep reported as more “refreshing” Pregabalin and Sleep
  32. 32.  RCT (n=370) • twice daily PGB • improved pain scores • improved sleep interference (sleep diaries) Van van Seventer et al 2006 Pregabalin, Pain and Sleep Interference in post-herpetic neuralgia
  33. 33.  Gabapentin  Tiagabine (Gabatril)  Xyrem (sodium oxybate, GHB)  Melatonin?  Cannabis? Other drugs that “improve” or increase deep (slow wave ) sleep
  34. 34. Fibromyalgia  Fibromyalgia common (3%?)  Defined by pain symptoms but sleep abnormal poor sleep efficiency, reduced stage 4 “alpha intrusions” into stage 4, fewer spindles (stage 2)  Several studies have looked at Pregabalin recent phase III, 748 patients, pain and sleep improved Mease et al, J Rheumatology (Mar 2008)  Sodium Oxybate also appears effective small open study (n=18) but sleep, pain and fatigue improved
  35. 35. Fibromyalgia  Very recent randomised controlled trial Moldofsky J Rheum 2010  195 FM patients randomised to oxybate (4.5, 6G) or placebo fatigue improved on VAS pre-Rx: sleep efficiency 76% SWS 41 min post-Rx: sleep efficiency 85% 6G SWS 61 min subjective sleep ratings correlated with pain scores
  36. 36. anxiety poor sleep pain Pain should not be treated in isolation DON’T FORGET SLEEP! quantity and quality...

×