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Review
. 2008 Oct;21(5):570-9.
doi: 10.1097/ACO.0b013e32830edbdf.

Neuron-glia crosstalk gets serious: role in pain hypersensitivity

Ke Ren  1 , Ronald Dubner
Affiliations
Review

Neuron-glia crosstalk gets serious: role in pain hypersensitivity

Ke Ren et al. Curr Opin Anaesthesiol. 2008 Oct.

Abstract

Purpose of review: Recent studies show that peripheral injury activates both neuronal and nonneuronal or glial components of the peripheral and central cellular circuitry. The subsequent neuron-glia interactions contribute to pain hypersensitivity. This review will briefly discuss novel findings that have shed light on the cellular mechanisms of neuron-glia interactions in persistent pain.

Recent findings: Two fundamental questions related to neuron-glia interactions in pain mechanisms have been addressed: what are the signals that lead to central glial activation after injury and how do glial cells affect central nervous system neuronal activity and promote hyperalgesia?

Summary: Evidence indicates that central glial activation depends on nerve inputs from the site of injury and release of chemical mediators. Hematogenous immune cells may migrate to/infiltrate the brain and circulating inflammatory mediators may penetrate the blood-brain barrier to participate in central glial responses to injury. Inflammatory cytokines such as interleukin-1beta released from glia may facilitate pain transmission through its coupling to neuronal glutamate receptors. This bidirectional neuron-glia signaling plays a key role in glial activation, cytokine production and the initiation and maintenance of hyperalgesia. Recognition of the contribution of the mutual neuron-glia interactions to central sensitization and hyperalgesia prompts new treatment for chronic pain.

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Figures

Fig. 1
Fig. 1
Schematic summary of recent findings on neuron-glial interactions in central sensitization and pain hypersensitivity. Note a synapse between an axon terminal and sensory neuron and close apposition of astrocytes and microglia. A. Signals leading to central glial activation: 1. Injury-generated input (small block arrows). 2. Chemical mediators released from nerve terminals (chemokines and neurotransmitters), damaged axons (MMP-3, MCP-1) and postsynaptic neurons (CCL21, DYN). 3. Hematogenous immune cells and inflammatory mediators. B. Activation of microglia. Note that activated microglia release a variety of mediators that in turn affect neuronal activity. C. Role of astroglia. Note the involvement of glutamate-glutamine shuttle and glutamate transport GLT-1, MMP-2 mediated cleavage/release of IL-1β, induction coupling of IL-1R signaling with NMDAR. Interactions between neurons and glia during nociceptive processing lead to amplified neuronal output and pain hypersensitivity. See text for further details. BK, bradykinin; CX43, connexin 43; D-ser, D-serine; DYN, dynorphin; EP2, prostaglandin E receptor subtype; gln, glutamine, glu, glutamate; GS, glutamine synthetase; KOR, kappa opioid receptor; P, phosphorylation.
See this image and copyright information in PMC

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