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Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression
Enrique J Cobos1, Chelsea A Nickerson2, Fuying Gao3
1Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine and Biomedical Research Center, University of Granada, 18071 Granada, Spain; Biosanitary Research Institute, University Hospital Complex of Granada, 18012 Granada, Spain.
Cell Reports
|February 2, 2018
Summary
Neuropathic pain involves distinct processes: cold hypersensitivity stems from sensory neurons, while tactile allodynia involves immune cells. This finding could lead to targeted drug development for different pain types.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Chronic neuropathic pain, a significant consequence of nerve injury, lacks complete mechanistic understanding.
- Allodynia, hypersensitivity to non-painful stimuli, is a hallmark symptom of neuropathic pain.
Purpose of the Study:
- To investigate the distinct mechanisms underlying cold hypersensitivity and tactile allodynia in neuropathic pain.
- To explore the temporal divergence and cellular basis of different pain hypersensitivity types following nerve injury.
Main Methods:
- Utilized a partial nerve injury mouse model to study neuropathic pain development.
- Analyzed global gene expression in dorsal root ganglia to identify correlating transcript changes.
- Employed selective cell ablation techniques (TrpV1 nociceptors, macrophages, T cells) to determine cellular contributions.
Main Results:
- Cold hypersensitivity onset preceded tactile allodynia, with distinct gene expression profiles.
- Nociceptor-related transcripts correlated with cold allodynia, while immune cell-centric transcripts correlated with tactile hypersensitivity.
- Ablation of TrpV1 nociceptors prevented cold allodynia, and immune cell depletion reduced tactile allodynia.
Conclusions:
- Neuropathic pain involves separate reactive processes in sensory neurons and immune cells, driving distinct hypersensitivity types.
- Understanding these divergent pathways offers potential for developing targeted therapies for specific neuropathic pain conditions.
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