JUSTUS- LIEBIGUNIVERSITÄTGIESSEN
Klinik und Poliklinik für Urologie und Kinderurologie
Klinik und Poliklinik für Urologie und KinderurologieUniversitätsklinikum Gießen und Marburg GmbH
- Standort Gießen -Justus-Liebig-Universität Gießen(Direktor: Prof. Dr. W. Weidner)
The role of inflammatory response andpain pathways in prostatitis
FME Wagenlehner
1. Acute bacterial Prostatitis
2. Chronic bacterial Prostatitis
3. Chronic Pelvic Pain Syndrom (CPPS)
3a. inflammatory
3b. non-inflammatory
4. Asymptomatic Prostatitis
NIH-Classification of the Prostatitis syndrome
National Institutes of Health: Chronic Prostatitis Workshop, Bethesda, Maryland, USA, 7.-8. Dez. 1995
1. Acute bacterial Prostatitis ∼ 0,1%
2. Chronic bacterial Prostatitis ∼ 1%
3. Chronic Pelvic Pain Syndrom (CPPS) ∼ 10%
3a. Inflammatory ∼ 2%
3b. non-inflammatory ∼ 8%
4. Asymptomatic Prostatitis ∼ 90%
NIH-Classification of the Prostatitis syndrome
National Institutes of Health: Chronic Prostatitis Workshop, Bethesda, Maryland, USA, 7.-8. Dez. 1995
1. Acute bacterial Prostatitis ∼ 0,1%
2. Chronic bacterial Prostatitis ∼ 1%
3. Chronic Pelvic Pain Syndrom (CPPS) ∼ 10%
3a. inflammatory ∼ 2%
3b. non-inflammatory ∼ 8%
4. Asymptomatic Prostatitis ∼ 90%
NIH-Classification of the Prostatitis syndrome
National Institutes of Health: Chronic Prostatitis Workshop, Bethesda, Maryland, USA, 7.-8. Dez. 1995
1. Acute bacterial Prostatitis ∼ 0,1%
2. Chronic bacterial Prostatitis ∼ 1%
3. Chronic Pelvic Pain Syndrom (CPPS) ∼ 10%
3a. inflammatory ∼ 2%
3b. non-inflammatory ∼ 8%
4. Asymptomatic Prostatitis ∼ 90%
NIH-Classification of the Prostatitis syndrome
National Institutes of Health: Chronic Prostatitis Workshop, Bethesda, Maryland, USA, 7.-8. Dez. 1995
CP/CPPS and clinical characteristics
40Sexual
63Abdominal
68Urinary
82Pain
%/ 764Symptoms
Bartoletti R et al., 2007 (Italian Prostatitis Study Group)
Pain
International Association for the study of pain, 1994
Unpleasant sensory and emotionalexperience associated with actual or
potential tissue damage, or described interms of such damage.
Pain
Protective response to tissue injury
Persistent pain is maladaptive
Chronic Pain
International Association for the study of pain, 1994
Pain that persists past the healing phasefollowing an injury.
Pain
• Acute 0 – 7 days
• Subacute 7 days – 3 months
• Chronic > 3 months
Pain characteristics
• Stimulus-evoked– Hyperalgesia (noxious stimulus)– Allodynia (non-noxious stimulus)
• Stimulus-independent– Burning– Paresthesia
Pain pathophysiology
• Nociceptive– Associated with tissue damage
(inflammation)• Neuropathic
– Associated with lesions in the nervous system(peripheral/ central)
• Mixed– Nociceptive + neuropathic
EAU guidelines 2008
Inflammation is the basic processwhereby tissues of the body
respond to injury
Immune system: basic principles• Innate (natural) system
– Responses always to same extent– Recognizes a few (10³) highly
conserved structures• Cells
– Phagocytic cells• Neutrophils• Monocytes• Macrophages
– Cells with inflammatory mediators• Basophils• Mast cells• Eosinophils
– Natural killer cells• Molecular components
– Complement proteins– Acute-phase proteins– Cytokines
• Acquired (adaptive) system– Responses improved on repeated
exposure– Recognizes multiple antigens (>107)
• Cells– Antigen-presenting cells
• Dendritic cells• Macrophages• B-lymphocytes
– Antigen-specific cells• B-lymphocytes• T-lymphocytes
• Molecular components– Antibodies– Cytokines
Thacker MA et al., 2007
Mendell JR et al., NEJM 2003
Apkarian AV et al. 2008
Chronic back pain
Post herpetic neuralgia
Pelvic pain (visceral pain)Osteoarthritis
Post herpetic neuralgia
Healthy acute pain
Nerves in the prostate
Doll A., Barcelona
Cytokines and chemokines in CPPS
• No correlation with most mediators• Macrophage inflammatory protein-1a (MIP-1a)
– Chemotactic and activating activity for macrophages– Elevated in rheumatoid arthritis, ulcerative colitis– role in inflammation-induced hyperalgesia
Desireddi NV, AJ Schaeffer et al., 2008
MIP-1a levels in EPS
Desireddi NV, AJ Schaeffer et al., 2008
CPSI pain score and MIP-1a
Desireddi NV, AJ Schaeffer et al., 2008
Autoimmune prostatitis in mice
•Von Frey filaments•Stimulation 10x•Response frequency
Rudick CN et al., 2008
Rat prostate suspension
Rudick CN et al., 2008
Inflammation scores
Control mice Autoimmune prostatitis mice
Rudick CN et al., 2008
Autoimmune prostatitis in mice
Rudick CN et al., 2008
Autoimmune prostatitis miceControl mice
Increased prostate neurite density
Rudick CN et al., 2008
Mast cells and nerves
Bunnett NW 2006
STIMULUS Mast CellsActivation
(Degranulation)
Cytokines PAR-2 Receptor
Pain spinal cord sensoricnerves(CGRP)
Aumüller and Meinhardt, 2002
Hypothesis of pain in CP/CPPS
Conclusion
• Pain most important symptom in CP/CPPS• Prostate inflammation can cause chronic
pain• Inflammation needs further characterisation• Causes need further study• Potential therapeutic targets
Liang R et al., 2007
Organ crosstalk
control
colitis
Liang R et al., 2007
control colitis
Thacker MA et al., 2007