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Updated: Jun 26, 2026
10:37
Development of Recombinant Proteins to Treat Chronic Pain
Published on: April 11, 2018
Chemokines and pain mechanisms
Catherine Abbadie1, Sonia Bhangoo, Yves De Koninck
1Department of Immunology, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. catherine_abbadie@merck.com
Brain Research Reviews
|January 17, 2009
Summary
New research identifies two key signaling pathways, CCL2/CCR2 and cathepsin S/CX3CL1/CX3CR1, involved in chronic pain development. Targeting these chemokine systems offers potential for novel neuropathic pain therapeutics.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Chronic pain, particularly neuropathic pain, significantly impacts quality of life.
- Astrocytes and microglia in the spinal cord play crucial roles in modulating pain signaling.
- Understanding neuron-glia communication is vital for developing effective pain treatments.
Purpose of the Study:
- To elucidate the signaling pathways mediating nociceptive spread from injured neurons to spinal microglia.
- To investigate the roles of CCL2/CCR2 and cathepsin S/CX3CL1/CX3CR1 pathways in neuropathic pain.
Main Methods:
- Utilized animal models of neuropathic pain following peripheral nerve injury.
- Examined changes at the first pain synapse in the spinal cord dorsal horn.
- Investigated the expression and function of chemokine systems (CCL2/CCR2, CX3CL1/CX3CR1).
- Administered selective antagonists to modulate chemokine activity.
Main Results:
- Identified two novel signaling pathways: chemotactic cytokine ligand 2 (CCL2)/CCR2 and cathepsin S/CX3CL1 (fractalkine)/CX3CR1.
- Demonstrated plasticity of these chemokine systems in the dorsal root ganglia and spinal cord.
- Showed that modulating these chemokines with antagonists reduced nociceptive behavior in rodent models.
Conclusions:
- The CCL2/CCR2 and cathepsin S/CX3CL1/CX3CR1 pathways are critical in neuron-to-glia communication in neuropathic pain.
- Up-regulation of these chemokines contributes to the development and maintenance of chronic pain.
- These chemokines and their receptors represent promising therapeutic targets for chronic pain management.
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