Neuromuscular

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MUSCLE PAIN & DISCOMFORT

Generalized
  Drugs
  Myopathic
  Non-muscle disorders
  Polymyalgia
Localized
  Cramps: Differential diagnosis
Pain medications
Principles
  Pain
  Muscle pain

Also see
  Painful neuropathies

GENERALIZED MUSCLE PAIN: Differential Diagnosis

Myopathic pain: Usually with High CK & Abnormal EMG; Weakness common Polymyalgia syndromes Muscle Cramps Non-muscle disorders

MUSCLE DISCOMFORT ± MYOPATHY: DRUGS & TOXINS
Inflammatory
Myopathy
Rhabdomyolysis
& High CK
± Chronic myopathy
Painful myopathy
± Rhabdomyolysis
Myalgia
± Myopathy
Cramps
Definite
Hydralazine
Penicillamine
Procainamide
L-tryptophan
  (impurity)


Possible
Cimetidine
Interferon-α
Ipecac
Leuprolide
Levodopa
Penicillin
Phenytoin
Propylthiouracil
Proton pump inhibitors
Sulfonamide
Alcohol
e-Amino Caproic Acid
Amphetamines
Anti-Psychotics
  Loxapine
  Quetiapine
Cocaine
Cyclosporine
Hypokalemia
Isoniazid
Lipid lowering agents
  Fibrates
    Bezafibrate
    Clofibrate
    Gemfibrozil
  Statins
    Lovastatin
    Simvastatin
    Pravastatin
    Fluvastatin
    Atorvastatin
    Cervistatin
    Red yeast rice
Lithium
Mibefradil
Neuroleptic-Malignant
Propofol
Zidovudine
Colchicine
Emetine
Germanium
Hypervitaminosis E
Taxenes
Zidovudine
All-Trans-Retinoic Acid
Azathioprine
Bryostatin 1
Captopril
Ciguatoxin
Corticosteroids
  Withdrawal
Cytotoxics
Danazol
Enlapril
Gemcitabine
Gold
Interferon α-2a
Interferon α-2b
Isotretinoin
Ketorolac
Labetalol
Methotrexate
Metolazone
Mycophenolate mofetil
Paclitaxel
Retinoids
Rifampin
Spanish toxic oil
Suxamethonium
  (Succinylcholine)
Tyrosine kinase inhibitors
Vinca alkaloids
Zimeldine
Albuterol
Anti-Cholinesterase
Bergamot (bergapten)
Caffeine
Clofibrate
Cyclosporine
Diuretics
Labetalol
Lithium
Nifedipine
Terbutaline
Tetanus
Theophylline
Vitamin A



Localized Muscle Pain



PAIN: Principles 3

Pain
  Categories
  Definitions
  Drugs
  Modulation
  Muscle
  Sensitization

Painful neuropathies
Nociceptive system
  Afferent neurons & axons
    Primary (PNS)
    Secondary (CNS)
  Descending pathways
  Pain perception
  Sensory terminals
    Nociceptor (axon) types
    Stimulus types
      Acid
      Chemical
      Temperature
      Mechanical
  Sensitization

Pain from noxious stimulation
of normal tissue


Definitions Pain Categories
  1. Nociceptive pain: Elicited by noxious stimulation of normal tissue
  2. Nociceptive pain: Elicited when tissue is in pathological state
  3. Neuropathic pain
Nociceptive system

Afferent neurons & axons
  Primary (PNS)
  Secondary (CNS)
Descending pathways
Pain perception
Sensory terminals
  Nociceptor (axon) types
  Stimulus types
    Acid
    Chemical
    Temperature
    Mechanical
Sensitization
Pain Modulation: Central mechanisms Pain Sensitization

Peripheral sensitization
Central sensitization
Chronic pain: Underlying mechanisms Drug treatment of pain: Principles

Mechanism Symptom Molecular targets Drugs
Na+ channels
  Accumulation
  Redistribution
  Altered expression
Spontaneous pain
Paresthesias
Neuroma sign
Na+ channels
  TTX-sensitive
  TTX-resistant
Carbamazepine
Lamotrigine
Mexilitine
Tricyclic antidepressants
Central
  sensitization
Hyperalgesia
  Tactile
  Cold
  Pin-prick
NMDA receptors
Neurokinin-1 receptors
nNOS
Protein kinase γ
NMDA antagonists
  Ketamine
  Dextramethorphan
  Amantidine
Peripheral
  sensitization
Hyperalgesia
  Pressure
  Thermal
Spontaneous pain
Neurogenic inflammation
Vanilloid receptor-1-desensitization
Neurokinin 1
Na+ channels: TTX-resistant
Nerve growth factor
Capsaicin
Sympathetic
  stimulation
Spontaneous pain α-receptor antagonists
Nerve growth factor/trKA
Phentolamine
Guanethidine
Increased transmission
  Reduced inhibition
Spontaneous pain
Hyperalgesia
Calcium channels, N-type
Receptors
Conotoxin
Opiates
Gabapentin
Clonidine
Tricyclic antidepressants
SNRIs

MUSCLE PAIN: Principles

Causes
  Drug-induced
Features
  Basic
  Clinical


Muscle Pain: Basic Features5 Muscle Pain: Clinical Features

Other myopathies with pain




POLYMYALGIA RHEUMATICA11

Diagnostic Criteria
  (Healy)
Persistent pain (> 1 month) involving two of : neck, shoulders, pelvic girdle
Morning stiffness (> 1 hour in duration)
Abrupt onset of illness (< 2 weeks)
Age: ≥ 50 years
Erythrocyte sedimentation rate > 40 mm/hr
Rapid response to prednisone (≤ 20 mg/day)
Absensce of other disorders



CHRONIC FATIGUE SYNDROME

CDC DEFINITION
Both major criteria, and either 8 minor symptom criteria, or 6 minor symptom criteria and 2 examination criteria

Major criteria Minor symptom criteria
  • Fever or chills: Mild
  • Sore throat
  • Lymph node pain
    • Cervical or axillary
  • Muscle discomfort or myalgia
  • Muscle weakness
    • Unexplained; Generalized
  • Fatigue: Generalized
    • After previously tolerated levels of exercise
    • Prolonged: > 24 hours
  • Headaches: New; Generalized
  • Arthralgias: Migratory; Non-inflammatory
  • Neuropsychiatric
    • Visual: Photophobia; Transient scotoma
    • Behavior: Forgetfulness; Irritablilty; Depression; Confusion
  • Sleep disturbance: Hyper- or Insomnia
  • Onset: Acute or subacute
Physical examination criteria COMMON SYMPTOMS & SIGNS
  • Systemic
    • Fever & Night sweats
    • Weight loss or gain
    • Lymph nodes: Swollen in neck
  • Respiratory
    • Onset: Sudden with flu-like illness
    • Sore throat; Cough
  • Musculoskeletal
    • Myalgias
    • Malaise: Postexertional
    • Arthralgias
    • Generalized subjective weakness
    • Morning stiffness
  • Neuropsychological
    • Awakening unrested
    • Concentration: Poor
    • Headaches
    • Forgetful
    • Depression or anxiety
    • Alcohol: Exacerbates symptoms
    • Tingling/Numbness in extremities
    • Photophobia
  • Functional status: Intermittently bedridden
ASSOCIATED DISORDERS

FATIGUE: Differential diagnosis


All-Trans-Retinoic Acid (ATRA)1
Myalgia Syndromes with No muscle pathology
bergapten
Bergapten
Bergamot oil 8
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References
1. Am Jour Hematol 2000;63:94-98
2. Balliere's Clinical Rheumatology 2000;14:797-811
3. Nature Neuroscience 2001;4:9-10,72-77,Nature 2001;203-210, Trends Neurosci 2003:26;643-645
4. Neurology 2001;57:149-152
5. Clin J Pain 2001;17:2-10
6. Inflamm Res 2002;51:393–402, Sports Med 2003;33:145-164
7. Nephrol Dial Transplant 2002;17:923-926
8. Lancet 2002;359:1484
9. Pain 2002;100:1-6
10. Nature Medicine 2001;7:821-826
11. Best Pract Res Clin Rheumatol. 2004;18:705-722, J Rheumatol 2005;32:65–73, Geriatrics 2004;59:39-44
12. J Clin Invest 2005;115:2393–2401
13. Autoimmunity Reviews 2004;3:46–53
14. Brain 2007 Oct 11
15. J Neurochem 2007 Oct 18
16. Pain 2009 Online August
17. Neuromuscular Disorders 2010;20:701-708
18.Leukemia Res 2012; Online June
19. Brain 2013; Online Dec

1/13/2014