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Neuropathic Pain: Central vs. Peripheral Mechanisms

  • Neuropathic Pain (E Eisenberg, Section Editor)
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Abstract

Purpose of Review

Our goal is to examine the processes—both central and peripheral—that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial. Here, we seek to identify evidence for PNS and CNS independently generating neuropathic pain signals.

Recent Findings

Recent preclinical studies in pNP support and provide key details concerning the role of multiple mechanisms leading to fiber hyperexcitability and sustained electrical discharge to the CNS. In studies regarding central mechanisms, new preclinical evidence includes the mapping of novel inhibitory circuitry and identification of the molecular basis of microglia-neuron crosstalk. Recent clinical evidence demonstrates the essential role of peripheral mechanisms, mostly via studies that block the initially damaged peripheral circuitry. Clinical central mechanism studies use imaging to identify potentially self-sustaining infra-slow CNS oscillatory activity that may be unique to pNP patients.

Summary

While new preclinical evidence supports and expands upon the key role of central mechanisms in neuropathic pain, clinical evidence for an autonomous central mechanism remains relatively limited. Recent findings from both preclinical and clinical studies recapitulate the critical contribution of peripheral input to maintenance of neuropathic pain. Further clinical investigations on the possibility of standalone central contributions to pNP may be assisted by a reconsideration of the agreed terms or criteria for diagnosing the presence of central sensitization in humans.

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Authors and Affiliations

  1. Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA

    Kathleen Meacham, Andrew Shepherd, Durga P. Mohapatra & Simon Haroutounian

  2. Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA

    Kathleen Meacham, Andrew Shepherd, Durga P. Mohapatra & Simon Haroutounian

Authors
  1. Kathleen Meacham
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  2. Andrew Shepherd
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  3. Durga P. Mohapatra
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  4. Simon Haroutounian
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Correspondence to Simon Haroutounian.

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Conflict of Interest

Kathleen Meacham declares training grant funding that provides part of her salary and involves research on painful neuropathies, but is otherwise unrelated to this manuscript, from the NIH - NIDDK T32 DK108742 01 IMAGING, MODELING AND ENGINEERING OF DIABETIC TISSUES.

Andrew Shepherd declares employment with and travel and accommodation expenses covered by Washington University School of Medicine.

Durga P. Mohapatra declares grant funding to conduct basic research in pain neurobiology from the National Institutes of Health (NIH), USA. Research grant no. NS069898.

Simon Haroutounian declares the ASPIRE neuropathic pain grant funding to his institution from Pfizer Inc. and travel reimbursement for NeuPSIG committee meeting from IASP.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Neuropathic Pain

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Meacham, K., Shepherd, A., Mohapatra, D.P. et al. Neuropathic Pain: Central vs. Peripheral Mechanisms. Curr Pain Headache Rep 21, 28 (2017). https://doi.org/10.1007/s11916-017-0629-5

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