Recomendations for the medicamentous treatment of chronic inflammatory rheumatic disease pain

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Recomendations for the medicamentous treatment of
chronic inflammatory rheumatic disease pain

• Dušan Logar
• Dpt.of Rheumatology,
• University Clinical Centre, Ljubljana

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Rheumatoid arthritis

• RA is a chronic, inflammatory, systemic,
  autoimmune disease
• Mainly polyarticular disease
• Chronic inflammation in synovial membrane of
  affected joints
• The specific cause of RA is unknown, but the
  immune response is well characterised

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Pain in RA

• 71 adults who are taking methotrexate, biologics
  or both, continued to report pain
• 55 these individuals had to modify their daily
  household activities
• Arthritis Foundation Survey 500 adult RA
  patients

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Pain in RA

• The extent of disability associated with chronic
  pain can vary from none to severe, and pain
  continue in the absence of tissue damage

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Interplay of various factors causing RA pain
Inflammatory mediators
Cytokines
Synovial fluid byochemical changes
Mechanical factors
Neural-immune system interplay
Glial cells
Circadian rythm of various hormons
Central sensitization
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Cells involved in articular inflammation
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Molecules involved in peripheral sensitization
Tissue damage
Inflammation
Sympathetic terminals
Sensitisizing cocteil
BRADYKININE PROSTAGLANDINES CYTOKINES
NA LEUCOTRIENES NERVE GROWTH FACTORS
Hydrogen ions HISTAMINE NEUROPEPTIDES
Potassium ions PURINES PROTEASES
Direct action on nociceptors
Sensitization of primary aferent neurons
Transduction sensitivity
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IL-1ß and TNF-a Proinflammatory Cytokines in the
Rheumatoid Joint
High endothelial venule
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Synovial membrane
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IL-8
PGE2
IL-6
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Capsule
Synovial space
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Pannus
Osteoblasts
Osteoclasts
B
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PGE2 prostaglandin-E2
Dinarello C, Moldawer L. Proinflammatory and
Anti-inflammatory Cytokines in Rheumatoid
Arthritis A Primer for Clinicians. 3rd ed.
Thousand Oaks, Ca, USA Amgen Inc. 2001.
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Interplay of various factors causing RA pain
Inflammatory mediators
Cytokines
Synovial fluid byochemical changes
Mechanical factors
Neural-immune system interplay
Glial cells
Circadian rythm of various hormons
Central sensitization
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Interplay of various factors causing RA pain
Inflammatory mediators
Cytokines
Synovial fluid byochemical changes
Mechanical factors
Neural-immune system interplay
Glial cells
Circadian rythm of various hormons
Central sensitization
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Inflammmatory rheumatic disease pain
Mast cell
ARTHRITIS
Neutrophil granulocyte
Macrophage
PHENOTYPIC SWITCH
PERIPHERAL SENSITIZATION CENTRAL
SENSITIZATION
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Treatment of chronic inflammatory rheumatic
disease pain

Zdravljenje bolecine pri revmatoidnem artritisu


GLUCOCORTICOIDS DMARs, BIOLOGICS
PARACETAMOL AND/OR NSAR, PARACETAMOL/TRAMADOL, OPI
OIDS

PAIN
INFLAMMATION
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Pharmacological approaches

• NSAIDs
• DMARDs
• Biologics
• Intraarticular long acting steroids
• opioids

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Pharmacological approaches

• NSAIDs
• DMARDs
• Biologics
• Intraarticular long acting steroids
• opioids

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NSARDs

• Effectivness evaluation after 14 days
• Concommitant prescription of second NSARD is not
  allowed
• Risk of prescription NSARD with long t/2 to older
  patients
• Low dose therapy in children and old adults
• Do not to ignore contraindications
• active ulcer disease
• ischaemic heart disease
• asthma, urticaria, angioedema
• advanced kidney disease

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Pharmacological approaches

• NSAIDs
• DMARDs
• Biologics
• Intraarticular long acting steroids
• opioids

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DMARDs

• Sulphasalasine
• Antimalarials
• Methotrexate
• Leflunomide
• Cyclosporine A

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Pharmacological approaches

• NSAIDs
• DMARDs
• Biologics
• Intraarticular long acting steroids
• opioids

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Biologics

• Infliximab
• Etanercept
• Adalimumab
• Rituximab
• Tociluzumab

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Pharmacological approaches

• NSAIDs
• DMARDs
• Biologics
• Intraarticular long acting steroids
• opioids

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Pharmacological approaches

• NSAIDs
• DMARDs
• Biologics
• Intraarticular long acting steroids
• opioids

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Opioids

• Treatment failure of therapy with NSARDs
• Contraindications for NSARDs
• Contraindications for corrective joint operation
• Patient long waiting on corrective joint operation

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Conclusions I

• 65 patients with RA state pain as the most
  important symptom of the disease
• For 75 of patients the still acceptable pain is
  graded with VAS between 0.5 and 2.0
• Agressive treatment of RA with DMARDs and
  biologics decreases the need of analgetic use
• Future targeted treatment with
• Drugs that have influence on various ionic
  channels
• a-2 agonists
• Drugs that have influence on prostaglandine and
  opioid receptors in spinal cord

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Conclusions II

• Pain that is consistenly present in any
  rheumatic condition should be considered a
  specific disease entity, which should be actively
  managed in parallel with the rheumatic complaint
• Fitzcharles MA, Shir Y. New concept in rheumatic
  pain. Rheum Dis Clin North Am 200834 267-83.