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Recomendations for the medicamentous treatment of chronic inflammatory rheumatic disease pain
Dušan LogarDpt.of Rheumatology,
University Clinical Centre, Ljubljana
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
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
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
Interplay of various factors causing RA pain
Cytokines
Mechanicalfactors
Glial cells
Central sensitization
Circadian rythm of various
hormons
Inflammatory mediators Synovial fluid
byochemical changes
Neural-immunesystem interplay
Cells involved in articular inflammation
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 nociceptorsSensitization of primary
aferent neuronsTransduction sensitivity
IL-1β and TNF-α: Proinflammatory Cytokines in the Rheumatoid Joint
Neutrophils
Osteoclasts
Bone
Cartilage
Osteoblasts
Chondrocytes
Bone
TNF- IL-1Synovial space
IL-6
PGE2
IL-8
High endothelial venule
Synovial membrane
Capsule
PannusOsteoblasts Osteoclasts
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.
Interplay of various factors causing RA pain
Cytokines
Mechanicalfactors
Glial cells
Central sensitization
Circadian rythm of various
hormons
Inflammatory mediators Synovial fluid
byochemical changes
Neural-immunesystem interplay
Interplay of various factors causing RA pain
Cytokines
Mechanicalfactors
Glial cells
Central sensitization
Circadian rythm of various
hormons
Inflammatory mediators Synovial fluid
byochemical changes
Neural-immunesystem interplay
Inflammmatory rheumatic disease pain
Macrophage
PERIPHERAL SENSITIZATION CENTRAL SENSITIZATION
PHENOTYPIC SWITCH
Neutrophil granulocyte
ARTHRITIS
Mast cell
CORRECTIVEJOINTOPERATIONS
PATIENT EDUCATION,PHYSICAL THERAPY,ORTHOSES, BALNEOTHERAPY
DAMAGE OFJOINTSTRUCTURES
PARACETAMOL AND/OR NSAR,PARACETAMOL/TRAMADOL,OPIOIDS
PAIN INFLAMMATION
GLUCOCORTICOIDSDMARs,BIOLOGICS
Zdravljenje bolečine pri revmatoidnem artritisu
Treatment of chronic inflammatory rheumatic disease pain
Pharmacological approaches
NSAIDs DMARDs Biologics Intraarticular long acting steroids opioids
Pharmacological approaches
NSAIDs DMARDs Biologics Intraarticular long acting steroids opioids
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
Pharmacological approaches
NSAIDs DMARDs Biologics Intraarticular long acting steroids opioids
DMARDs
Sulphasalasine Antimalarials Methotrexate Leflunomide Cyclosporine A
Pharmacological approaches
NSAIDs DMARDs Biologics Intraarticular long acting steroids opioids
Biologics
Infliximab Etanercept Adalimumab Rituximab Tociluzumab
Pharmacological approaches
NSAIDs DMARDs Biologics Intraarticular long acting steroids opioids
Pharmacological approaches
NSAIDs DMARDs Biologics Intraarticular long acting steroids opioids
Opioids
Treatment failure of therapy with NSARDs Contraindications for NSARDs Contraindications for corrective joint
operation Patient long waiting on corrective joint
operation
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 α-2 agonists Drugs that have influence on prostaglandine and opioid
receptors in spinal cord
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 2008;34: 267-83.
