Fibromyalgia and Chronic Fatigue Syndrome

FibromyalgiaPart 1

Marcus Webb

The NutriCentre, Park CrescentFebruary 1st 2012

(Fibromyalgia Part 2 scheduled for 6th June 2012)

Where do you start?Where do you start?

What is it?What is it?

Why does it occur?Why does it occur?

Can it be treated?Can it be treated?

Is it curable? Is it curable?

11 out of the 18 needed

• Occiput• C5-C7 region• Mid-trapezius• Supraspinatus• 2nd rib, costochondral area• Lateral epicondyle• Gluteal upper quadrant• Greater trochanter• Knees, medial fat pad

Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33(2):160-72.

Some history & background

• UK prevalence: 2.0 – 4.7 %

• Second only to OA as a cause of chronic pain

• Diagnosed 7 x more frequently in women • Typical age range 45-60

• No diagnostic tests (X-rays, scans, blood tests)

• Diagnosis of exclusion to be on the safe side

• Confirmed by clinical & physical examination

• Regular review needed to check for symptom changes

White KP, Harth M. Classification, epidemiology, and natural history of fibromyalgia. Curr Pain Headache Rep. 2001;5(4):320-9.Gran JT. The epidemiology of chronic generalized musculoskeletal pain. Best Pract Res Clin Rheumatol. 2003;17(4):547-61.Expert Panel And Consensus Panel Myopain 1992. Consensus Document On Fibromyalgia: The Copenhagen Declaration.Fibromyalgia Association UK. Guidance on management of Fibromyalgia for the multidisciplinary team.

Some history & background

• UK prevalence: 2.0 – 4.7 %

• Second only to OA as a cause of chronic pain

• Diagnosed 7 x more frequently in women • Typical age range 45-60

• No diagnostic tests (X-rays, scans, blood tests)

• Diagnosis of exclusion to be on the safe side

• Confirmed by clinical & physical examination

• Regular review needed to check for symptom changes

White KP, Harth M. Classification, epidemiology, and natural history of fibromyalgia. Curr Pain Headache Rep. 2001;5(4):320-9.Gran JT. The epidemiology of chronic generalized musculoskeletal pain. Best Pract Res Clin Rheumatol. 2003;17(4):547-61.Expert Panel And Consensus Panel Myopain 1992. Consensus Document On Fibromyalgia: The Copenhagen Declaration.Fibromyalgia Association UK. Guidance on management of Fibromyalgia for the multidisciplinary team.

Thoughts & observations

There is no real agreement on what actually causes FM

There are some very strong associations between FM and another rather mysterious chronic condition; CFS – (NB. ME is not CFS)

However, there appears to be some common themes in both;

• Sleep disturbance• Anxiety syndromes / depression• Subtle changes in metabolic hormones such as thyroid & cortisol• Low blood pressure• Exposure to a traumatic event or illness – physical or emotional• Irritable bowel and/or irritable bladder (interstitial cystitis)• Subtle changes in carbohydrate metabolism / glucose regulation

Thoughts & observations

There is no real agreement on what actually causes FM

There are some very strong associations between FM and another rather mysterious chronic condition; CFS – (NB. ME is not CFS)

However, there appears to be some common themes in both;

• Sleep disturbance• Anxiety syndromes / depression• Subtle changes in metabolic hormones such as thyroid & cortisol• Low blood pressure• Exposure to a traumatic event or illness – physical or emotional• Irritable bowel and/or irritable bladder (interstitial cystitis)• Subtle changes in carbohydrate metabolism / glucose regulation

Fibromyalgia part 1 (Today) will focus on;

• A review of possible causal factors

• A review of 2 key symptoms;

1. Pain2. Sleep disturbance

•Practical management tips

Fibromyalgia part 1 (Today) will focus on;

• A review of possible causal factors

• A review of 2 key symptoms;

1. Pain2. Sleep disturbance

Fibromyalgia part 2 (6th June 2012) will focus on;

• A review of any advances since part 1’s talk

• A review of;

1. Mood disorder, anxiety & depression2. Low blood pressure3. Irritable bowel & interstitial cystitis

Fibromyalgia part 2 (6th June 2012) will focus on;

• A review of any advances since part 1’s talk

• A review of;

1. Mood disorder, anxiety & depression2. Low blood pressure3. Irritable bowel & interstitial cystitis

Causes

Causes 1.

Genetic

There is evidence that genes involved in the serotonin and dopamine systems can exist in many forms play a role in the development of FMS.

These ‘polymorphisms’ are not specific for FMS and are also associated with other functional disorders and depression.

Causes 1.

Genetic

There is evidence that genes involved in the serotonin and dopamine systems can exist in many forms play a role in the development of FMS.

These ‘polymorphisms’ are not specific for FMS and are also associated with other functional disorders and depression.

The genetic - neuroendocrine cascade

Causes 3.

Stress triggers

Home / work / kids / relationships… life!

Change of life / work / domestic circumstance

Loss of ‘control’ over life events / work events

Illness – chronic or acute

Trauma – RTA, trivial falls, surgery…

Any combination of the above to the threshold of ‘tipping point’

Stress reaction: Alarm phase, fatigue phase, exhaustion phase

Causes 3.

Stress triggers

Home / work / kids / relationships… life!

Change of life / work / domestic circumstance

Loss of ‘control’ over life events / work events

Illness – chronic or acute

Trauma – RTA, trivial falls, surgery…

Any combination of the above to the threshold of ‘tipping point’

Stress reaction: Alarm phase, fatigue phase, exhaustion phase

Metabolic effects

StressStress

Anterior pituitary

Kidney

Adrenal gland

Hypothalamus

CortisolCortisol

ACTHACTH

CRHCRH

NormalHypothalamic Pituitary Axis response to

stress

Metabolic effects

StressStress

Anterior pituitary

Kidney

Adrenal gland

Hypothalamus

CortisolCortisol

ACTH ACTH

CRHCRH

“Blunted”Hypothalamic Pituitary

Axis response to chronic / unresolved

stress

NB: Pregnenolone is derived from cholesterol and is the precursor of DHEA… the building block for all other steroid hormones; eg. sex hormones, gluco and mineralocorticoids

Cushing’sdisease

Normal physiology progressing toStage 1 – Stage 2 – Stage 3

adrenal functional adoptions

Normal physiology progressing toStage 1 – Stage 2 – Stage 3

adrenal functional adoptions

Addison’sdisease

Pathologic state of high

cortisol

Pathologic state of high

cortisol

Pathologic state of low

cortisol

Pathologic state of low

cortisol

Natural Adaptive physiology

• Fatigue & weakness• Low BP / heart rate• Dark skin patches• Chronic diarrhoea• Loss of appetite • Salt craving• Sluggish movements• Weight loss• Low Na & high K• Normal sex steroids• Painful muscles• Irritable / depressed• Sweating• Headaches• 90% of cortex to be damaged in Addison’s

• ‘Lemon on match sticks’ appearance• Puffy face & hirsuit • Thin easily bruised skin• Heavy sweating• Slow healing• Infertility, low libido• High blood sugars• Osteoporosis• Weight gain• Depression / mood swings• High thirst / DM• High BP• Low K & high Na

The Cortisol Spectrum

Normal adrenal stress profileNormal adrenal stress profile

Stage 1. The acute ‘Alarm-Phase’Stage 1. The acute ‘Alarm-Phase’

Stage 1. The acute ‘Alarm-Phase’ profileStage 1. The acute ‘Alarm-Phase’ profile

Stage 1. Alarm (acute) phase - Super Hero Phase

Achiever, super efficient

Perfectionist / type-A personality

Multitasking

Thriving on challenges / deadlines

Exercises regularly

Stage 1. Alarm (acute) phase - Super Hero Phase

Achiever, super efficient

Perfectionist / type-A personality

Multitasking

Thriving on challenges / deadlines

Exercises regularly

Stage 2. Adrenal ‘fatigue’Stage 2. Adrenal ‘fatigue’

Stage 2. Adrenal ‘fatigue’ profileStage 2. Adrenal ‘fatigue’ profile

Stage 2. Adrenal Fatigue – Cracks starting to show phase

Getting cranky

Loosing focus

Memory suffering / ‘brain fog’

Sleep disturbance starting… fatigued but can’t sleep

Eating pattern / food choices changing

Starting to notice fatigue setting in

Notices unfamiliar aches and pains

Stage 2. Adrenal Fatigue – Cracks starting to show phase

Getting cranky

Loosing focus

Memory suffering / ‘brain fog’

Sleep disturbance starting… fatigued but can’t sleep

Eating pattern / food choices changing

Starting to notice fatigue setting in

Notices unfamiliar aches and pains

Stage 3. Adrenal ‘exhaustion’Stage 3. Adrenal ‘exhaustion’

Stage 3. Adrenal ‘exhaustion’ profileStage 3. Adrenal ‘exhaustion’ profile

Stage 3. Adrenal Exhaustion – Crash & burn phase

Sleep deregulation

Medically unexplained fatigue

Medically unexplained digestive upsets

Medically unexplained pain syndromes

Medically unexplained Immune dysfunction

Medically unexplained infection prone system

Mood disorder

CFS / FM

Stage 3. Adrenal Exhaustion – Crash & burn phase

Sleep deregulation

Medically unexplained fatigue

Medically unexplained digestive upsets

Medically unexplained pain syndromes

Medically unexplained Immune dysfunction

Medically unexplained infection prone system

Mood disorder

CFS / FM

Normal individuals taking regular exercise

Brief phase of exercise deprivation (7 days)

No effects

FatigueMood disturbance

Muscular pains

FatigueMood disturbance

Muscular pains Prior to exercise deprivation this group also had

asymptomatic;

Hypo-functioning HPAANS disturbance

Low NK cell responsiveness

Prior to exercise deprivation this group also had

asymptomatic;

Hypo-functioning HPAANS disturbance

Low NK cell responsiveness

A novel model

Pre-existing hypo-active stress regulating systemPre-existing hypo-active stress regulating system

J. Psychosom Res 2004;57:391-8Trends Endocrinol Metab 2004;15:55-9J Psychosom Res 2001;51:571-6

A dysfunction in the stress-regulating systems may antedate the onset of FM/CFS

Concept supported by the characteristic history of a pre-morbid lifestyle characteristics

Sufferers appear to have a need to hyper-stimulate their hypo-responsive systems to obtain a feeling of well-beingSufferers appear to have a need to hyper-stimulate their hypo-responsive systems to obtain a feeling of well-being

“Never could sit still…”“I always kept very busy…”

“I needed the gym even after a busy day…”“I thrived on challenges and problem solving…”

“Never could sit still…”“I always kept very busy…”

“I needed the gym even after a busy day…”“I thrived on challenges and problem solving…”

Burn OutCFS/FM

Phase between awake &

Increase BP, temp & breathing

relaxed muscles

Increase BP, temp & breathing

relaxed muscles

Heart & brain slows

Lower body temp & BP drops

Repair phaseRepair phase

Stage-1 (slow theta waves)

Stage-2 (bursts of spindle waves)

Stage-3 (slow delta waves, transition phase before deep sleep)

Stage-4 (deep delta sleep)

Stage-5 (REM sleep)

5-15 mins

20 mins into delta sleep

30 mins into deep sleep

The Sleep Cycle4-6 cycles per night

90-110 mins per cycle

Sleep disturbance

Over three quarters of FM patients suffer from non-restorative sleep

Interestingly, sleep deprivation in normal subjects induces myalgic symptoms that resemble FM

In normal folk sleep induces;

1. A reduced SNS activity

1. Promotion of PNS activity

1. Transient reduction in circulating cortisol

Moldofsky H. Management of sleep disorders in fibromyalgia. Rheum Dis Clin North Am. 2002;28(2):353-65.Moldofsky H, Scarisbrick P, England R, Smythe H. Musculosketal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med. 1975;37(4):341-51.Meerlo P, Koehl M. Sleep restriction alters the HPA response to stress. J Neuroendrcrinology. 14 (2002):397-402

Sleep disturbance

Over three quarters of FM patients suffer from non-restorative sleep

Interestingly, sleep deprivation in normal subjects induces myalgic symptoms that resemble FM

In normal folk sleep induces;

1. A reduced SNS activity

1. Promotion of PNS activity

1. Transient reduction in circulating cortisol

Moldofsky H. Management of sleep disorders in fibromyalgia. Rheum Dis Clin North Am. 2002;28(2):353-65.Moldofsky H, Scarisbrick P, England R, Smythe H. Musculosketal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med. 1975;37(4):341-51.Meerlo P, Koehl M. Sleep restriction alters the HPA response to stress. J Neuroendrcrinology. 14 (2002):397-402

A good sleepA good sleep

HypothalamusHypothalamus

CRHCRHCIFCIF

PituitaryPituitary

Adrenal Cortex

Reduced CortisolReduced Cortisol

CIF – corticotropin inhibiting factor

CRH – corticotropin releasing hormone

ACTH – adrenocorticotrophic hormone

Inhibits release of cortisol release

Normal Sleep Profile

Sleep disturbance / poor sleep

Poor or disturbed sleep is associated with;

1. SNS activation

1. Changes the ways the neuroendocrine system reacts to stress

1. In acute states: Increase in circulating cortisol

1. In acute states: High cortisol levels are associated with ‘brain fog’ in which the normal functioning of the frontal lobes are influenced by the uncoordinated activity of other cortical regions

1. In chronic states: Reduction in number of brain system serotonin receptors and dysfunctional cortisol awakening response (CAR).

• A shift in brain system function towards that of a true mood disorder

Meerloa P, Sgoifob A, Sucheckic D. Restricted and disrupted sleep: Effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Medicine Reviews (2008) 12, 197–210

Drummond S, Brown G. Altered brain response to verbal learning following sleep deprivation. Nautre. 403 (2000):655

Sleep disturbance / poor sleep

Poor or disturbed sleep is associated with;

1. SNS activation

1. Changes the ways the neuroendocrine system reacts to stress

1. In acute states: Increase in circulating cortisol

1. In acute states: High cortisol levels are associated with ‘brain fog’ in which the normal functioning of the frontal lobes are influenced by the uncoordinated activity of other cortical regions

1. In chronic states: Reduction in number of brain system serotonin receptors and dysfunctional cortisol awakening response (CAR).

• A shift in brain system function towards that of a true mood disorder

Meerloa P, Sgoifob A, Sucheckic D. Restricted and disrupted sleep: Effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Medicine Reviews (2008) 12, 197–210

Drummond S, Brown G. Altered brain response to verbal learning following sleep deprivation. Nautre. 403 (2000):655

Stress / SNSStress / SNS

HypothalamusHypothalamus

CRHCRHCIFCIF

PituitaryPituitary

Adrenal Cortex

Increased Cortisol

CIF – corticotropin inhibiting factor

CRH – corticotropin releasing hormone

ACTH – adrenocorticotrophic hormone

Stimulates release of CRH & enhances cortisol release

Inhibits release of CIF and facilitates cortisol release

Acute phase Sleep Disturbance

In chronic or unresolved stress situations

Loss of the predictable peak level (50-75% increase on awakening level) normally seen 30 mins after awakening.

Tests for morning cortisol levels best taken on a typical day, not over a holiday or atypical day so it accurately reflects a ‘real-life’ cortisol awakening response (CAR).

In chronic or unresolved stress situations

Loss of the predictable peak level (50-75% increase on awakening level) normally seen 30 mins after awakening.

Tests for morning cortisol levels best taken on a typical day, not over a holiday or atypical day so it accurately reflects a ‘real-life’ cortisol awakening response (CAR).

Normal range

Flattened CAR

On awakening 10 mins later 20 mins later 30 mins later(normally peek level)

60 mins later

Cortisol Awakening ResponseCortisol Awakening Response

Practical tips for sleep management – the basics

Do not consume alcohol near bedtime or caffeine after 4:00 pm.

Avoid ‘stimulus’ in the late evenings – TV, radio, music, computer…

Don’t go to bed too early!

Understand that with increasing age the need for sleep can reduce.

Do not use your bed for problem solving or doing work.

Care with fluids to avoid nocturnal bladder activity!

Turn the bedside clock round to avoid ‘clock-watching’

Turkey roll and glass of milk… the tryptophan trick

Take a hot bath before bed.

Keep your bedroom cool.

Practical tips for sleep management – the basics

Do not consume alcohol near bedtime or caffeine after 4:00 pm.

Avoid ‘stimulus’ in the late evenings – TV, radio, music, computer…

Don’t go to bed too early!

Understand that with increasing age the need for sleep can reduce.

Do not use your bed for problem solving or doing work.

Care with fluids to avoid nocturnal bladder activity!

Turn the bedside clock round to avoid ‘clock-watching’

Turkey roll and glass of milk… the tryptophan trick

Take a hot bath before bed.

Keep your bedroom cool.

Practical tips for sleep management – useful natural remedies

500mg Calcium & 200mg Magnesium taken at bedtime.

200 – 300mg Elthea-100 containing L-theanine (Enzymatic Therapy, USA) taken half an hour before bed.

500mg Phosphatidylserine (Nature’s Way, USA) taken 4 hours before bed.

50 – 200mg enteric coated 5-HTP (Webber, Canada) 1 hr before sleep – give it 4-6 weeks to work, don’t use if on antidepressants.

1-3 x capsules Dr T’s sleep formula (Enzymatic Therapy, USA) – wild lettuce, hops, Jamacian dog wood, valerian taken 30 – 90 mins before bed.

Delta wave sleep CD…

Practical tips for sleep management – useful natural remedies

500mg Calcium & 200mg Magnesium taken at bedtime.

200 – 300mg Elthea-100 containing L-theanine (Enzymatic Therapy, USA) taken half an hour before bed.

500mg Phosphatidylserine (Nature’s Way, USA) taken 4 hours before bed.

50 – 200mg enteric coated 5-HTP (Webber, Canada) 1 hr before sleep – give it 4-6 weeks to work, don’t use if on antidepressants.

1-3 x capsules Dr T’s sleep formula (Enzymatic Therapy, USA) – wild lettuce, hops, Jamacian dog wood, valerian taken 30 – 90 mins before bed.

Delta wave sleep CD…

Phosphatidylserine (PS) & acute stress/cortisol management

Placebo given with exercise (cycling) to simulate biological stress, known to increase ACTH & Cortisol levels as seen in this response curve

50 and 75mg PS given with exercise (cycling) to simulate biological stress but the ACTH/Cortisol response is significantly ‘blunted’.

Neuroendocrinology.1990; 52:243-248

L-Theanine – a great ‘leveler’

Significant increase in Alpha-wave propagation following 30-40 mins ingestion of between 50-200mg L-theanine

Trends Food Sci Tech 1999; 10:199-204.Alternative & Complementary Therapies 2001,April; 7:91-95

InjuryInjury

Peripheral nerve

Dorsal horn

Descending (modulating) pathway

Ascending pathway

PainPain

Basic Pain Pathway; basic scheme

Mayo Clin Proc. 2011;86(9):907-911

Descending (modulating) pathway

Ascending pathway

Peripheral nerve

InjuryInjury

PainPain

Pain gate in dorsal horn

Interneuron

Basic Pain Pathway; the pain gate

Pain gate neurons contains complex mixture of;

1.Opioid receptors2.GABA receptors3.Glutamate receptors4.5-HT receptors

Pain gate neurons contains complex mixture of;

1.Opioid receptors2.GABA receptors3.Glutamate receptors4.5-HT receptors

Higher centers regulate the amount of descending control on the pain gate; complex personal and experiential influences.

The effects of weather (changes in atmospheric pressure) on FM and rheumatic pain

Annals of Rheumatic Diseases 1990; 49: 158-159

Weather conditions significantly influence day-to-day symptoms in FM patients

Practical tips for pain management – Anti-inflammatory diet

Practical tips for pain management – useful natural remedies

1000 – 4000mg Fish oils (Nature’s Way Mega-EFA) : DHA & EPA, good evidence.

200-600mg Magnesium (citrate, chelate or glycinate) : Mixed evidences, may also help with migraines, care with high dose… lose bowels!

1000-2000iu Vitamin D3 : low levels associated with chronic pain syndromes.

1000 – 2000mg methylsufonylmethane (Opti-MSM, Hadley Wood Healthcare) : long history of use in pain and allergy management, mixed reviews but safe.

500 – 1000mg Acetyl-L-carnitine (Nature’s Way, USA) : especially useful in nerve pain & diabetic neuropathy as well as cellular (mitochondrial) ATP synthesis from dietary fats.

50 – 300mg Alpha-lipoic acid (Nature’s Way, USA) : especially useful in nerve pain & diabetic neuropathy, may even slow the progression of nerve damage.

500 – 1500mg Celadrin (Hadley Wood Healthcare): especially good for joint pain & ‘stiffness’