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Two-photon Imaging of Microglial Processes' Attraction Toward ATP or Serotonin in Acute Brain Slices
Published on: January 31, 2019
ATP receptors of microglia involved in pain
1Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Abstract:
Microglia, activated when physiological homeostasis is threatened, play an important role as immune cells in the CNS. Activated microglia show a progressive series of changes in morphology, gene expression, function and number, and produce and release various chemical mediators, including proinflammatory cytokines that can produce immunological actions and modify neuronal function. Recently, accumulating evidence has indicated an important role for ATP receptors of activated microglia in neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, cancer, diabetes or infection. The expression of the P2X4 receptor, a subtype of ATP receptors, is enhanced in spinal microglia in a peripheral nerve injury model, and blocking pharmacologically and suppressing molecularly P2X4 receptors produces a reduction of the neuropathic pain. Several cytokines such as interleukin 6 (IL6) and tumour necrosis factor alpha (TNFalpha) in the dorsal horn are also increased after nerve lesion and have been implicated in contributing to nerve-injury pain. ATP can activate mitogen-activated protein kinase (MAPK) leading to the release of bioactive substances including cytokines from microglia. Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain.
Insights
Activated microglia and their ATP receptors, like P2X4, are key players in neuropathic pain development. Targeting these receptors offers a potential therapeutic strategy for nerve injury pain.
Area of Science:
- Neuroscience
- Immunology
Background:
- Microglia are CNS immune cells activated by threats to homeostasis.
- Activated microglia release mediators, including pro-inflammatory cytokines, influencing neuronal function.
- ATP receptors on activated microglia are increasingly linked to neuropathic pain.
Purpose of the Study:
- To investigate the role of ATP receptors, specifically P2X4, in microglia activation and neuropathic pain.
- To explore the involvement of cytokines like IL-6 and TNF-alpha in nerve injury pain.
Main Methods:
- Examined P2X4 receptor expression in spinal microglia following peripheral nerve injury.
- Investigated the effects of pharmacological and molecular suppression of P2X4 receptors.
- Assessed changes in cytokine levels (IL-6, TNF-alpha) in the dorsal horn post-nerve lesion.
Main Results:
- P2X4 receptor expression is upregulated in spinal microglia after peripheral nerve injury.
- Pharmacological and molecular blockade of P2X4 receptors reduced neuropathic pain.
- Increased levels of IL-6 and TNF-alpha were observed in the dorsal horn post-nerve lesion.
- ATP stimulation of microglia via purinergic receptors activates MAPK, leading to cytokine release.
Conclusions:
- Activated microglia and their P2X4 ATP receptors play a significant role in neuropathic pain.
- Targeting P2X4 receptors and associated cytokine pathways presents a potential therapeutic avenue for neuropathic pain management.
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