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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
CXCR4 signaling mediates morphine-induced tactile hyperalgesia
Natalie M Wilson1, Hosung Jung, Matthew S Ripsch
1Department of Molecular Pharmacology and Therapeutics, Loyola University of Chicago, Maywood, IL 60153, USA.
Brain, Behavior, and Immunity
|January 4, 2011
Summary
Opioid-induced hyperalgesia (OIH) may involve chemokine signaling. Blocking CXCR4 with AMD3100 reversed OIH in rats, suggesting SDF1/CXCR4 signaling is key to opioid-induced pain sensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioids are primary treatments for moderate to severe pain.
- Chronic opioid use can lead to opioid-induced hyperalgesia (OIH), increasing pain sensitivity.
- The mechanisms of OIH are not fully understood but may involve gene expression changes and chemokine signaling.
Purpose of the Study:
- To investigate the role of chemokine signaling in opioid-induced hyperalgesia (OIH).
- To characterize changes in chemokine and receptor expression in sensory neurons after chronic morphine treatment.
- To evaluate the therapeutic potential of targeting chemokine signaling for OIH management.
Main Methods:
- Assessed mRNA expression of stromal-derived factor-1 (SDF1/CXCL12) in rat dorsal root ganglion (DRG) neurons after chronic morphine sulfate treatment.
- Examined chemokine release in F11 neuroblastoma-sensory neuron hybrid cells.
- Investigated CXCR4 expression in DRG neurons and satellite glial cells.
- Administered the CXCR4 antagonist AMD3100 to rats and assessed its effect on tactile hyperalgesia.
Main Results:
- Chronic morphine treatment upregulated SDF1/CXCL12 mRNA expression in rat sensory neurons.
- SDF1 release was constitutive, while monocyte chemoattractant protein-1 (MCP1/CCL2) release was activity-dependent.
- Increased functional CXCR4 expression was observed in DRG sensory neurons post-morphine treatment.
- Intraperitoneal administration of AMD3100 completely reversed OIH in rats.
Conclusions:
- Opioid-induced SDF1/CXCR4 signaling is central to the development of long-lasting OIH.
- Targeting the SDF1/CXCR4 pathway with antagonists offers a promising strategy for managing opioid-induced hyperalgesia.
- This research provides a novel therapeutic approach for chronic pain management side effects.
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