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Nociceptor subpopulations involved in hyperalgesic priming.
L F Ferrari1, O Bogen, J D Levine
1Division of Neuroscience, Departments of Medicine and Oral and Maxillofacial Surgery, University of California, 521 Parnassus Avenue, San Francisco, CA 94143-0440, USA.
Neuroscience
|November 26, 2009
Summary
Hyperalgesic priming, a model for chronic pain, involves neuroplastic changes. This study reveals priming occurs in both nonpeptidergic and peptidergic pain-sensing nerve cells, mediated by protein kinase C epsilon (PKCε).
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Hyperalgesic priming is a rat model for the transition from acute to chronic pain.
- It involves long-lasting neuroplastic changes in signaling pathways.
- Priming prolongs pro-inflammatory cytokine-induced nociceptor sensitization and mechanical hyperalgesia.
Purpose of the Study:
- To test the hypothesis that hyperalgesic priming is restricted to isolectin B4 (IB4)(+)-nonpeptidergic nociceptors.
- To investigate the role of protein kinase C epsilon (PKCε) in hyperalgesic priming.
- To determine if hyperalgesic priming occurs in both IB4(+) and receptor tyrosine kinase (TrkA)(+) nociceptor subpopulations.
Main Methods:
- Development of a rat model for acute to chronic pain transition (hyperalgesic priming).
- Investigated the role of PKCε activation in the peripheral terminal of primary afferent nociceptors.
- Examined hyperalgesic priming induced by prostaglandin E2 (PGE2) after nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF) treatments.
Main Results:
- Hyperalgesic priming, characterized by PKCε-dependent, prolonged hyperalgesia, was observed.
- Priming occurred in both IB4(+)-nonpeptidergic and TrkA(+)-peptidergic nociceptor subpopulations.
- While PKCε inhibition prevented NGF-induced priming, NGF-induced hyperalgesia itself was PKCε-independent.
Conclusions:
- Hyperalgesic priming is not restricted to a single nociceptor subpopulation.
- Separate intracellular pools of PKCε may mediate nociceptor sensitization and hyperalgesic priming induction.
- This finding advances understanding of the neurobiological mechanisms underlying chronic pain development.
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