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Updated: Mar 3, 2026
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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
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Neuropathic Pain: Central vs. Peripheral Mechanisms.
Kathleen Meacham1,2, Andrew Shepherd1,2, Durga P Mohapatra1,2
1Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
Current Pain and Headache Reports
|April 23, 2017
Summary
Peripherally-induced neuropathic pain (pNP) involves both peripheral nervous system (PNS) and central nervous system (CNS) mechanisms. While PNS damage initiates pain, CNS processes are crucial for its persistence, though autonomous central pain generation requires further clinical investigation.
Area of Science:
- Neuroscience
- Pain Research
- Neurology
Background:
- Peripherally-induced neuropathic pain (pNP) originates from damage to the peripheral nervous system (PNS).
- The persistence of pNP often involves maladaptive processes within the central nervous system (CNS).
- Understanding the interplay between PNS and CNS is critical for developing effective neuropathic pain treatments.
Purpose of the Study:
- To examine the central and peripheral mechanisms underlying the development and maintenance of pNP.
- To review recent evidence supporting the roles of both PNS and CNS in generating neuropathic pain signals.
- To assess the potential for autonomous pain-generating mechanisms within the CNS.
Main Methods:
- Review of recent preclinical studies detailing mechanisms of fiber hyperexcitability and sustained electrical discharge.
- Analysis of preclinical evidence on central mechanisms, including inhibitory circuitry and microglia-neuron interactions.
- Examination of clinical evidence, including studies blocking peripheral circuitry and neuroimaging of central nervous system activity.
Main Results:
- Preclinical studies confirm multiple mechanisms contributing to peripheral fiber hyperexcitability and CNS signaling.
- Novel preclinical findings include mapping inhibitory circuitry and identifying molecular pathways in microglia-neuron crosstalk.
- Clinical evidence highlights the essential role of peripheral mechanisms, while direct clinical evidence for autonomous central mechanisms remains limited.
Conclusions:
- Both peripheral nervous system (PNS) and central nervous system (CNS) contribute significantly to neuropathic pain.
- Peripheral input is critical for the maintenance of neuropathic pain, as supported by both preclinical and clinical findings.
- Further clinical research, potentially with revised diagnostic criteria for central sensitization, is needed to fully elucidate standalone central contributions to pNP.
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