New Evidence Linking IL-17 to Neuropathic Pain

New Evidence Linking IL-17 to Neuropathic Pain

A study published in Molecular Medicine Reports provides further evidence that interleukin (IL)-17 contributes to neuropathic pain through the activation of astrocytes and secretion of proinflammatory cytokines.

Neuropathic pain or chronic pain is a disease syndrome caused by injury to peripheral nerves, the spinal cord or the brain and over 1.5 billion people suffer from this condition. Neuropathic pain and neuropathic pain syndromes include deafferentation pain, diabetic, cancer and ischemic neuropathies, trigeminal neuralgia and nerve injury caused by surgery or trauma. This also includes central nervous system injury (multiple sclerosis, spinal cord injury) and viral infections (e.g. postherpetic neuralgia).

Several pro-inflammatory cytokines contribute to neuropathic pain and hyperalgesia. This includes IL-1β, tumor necrosis factor (TNF), IL-6 and IL-8. Cytokines and chemokines are released by neurons, microglia, astrocytes, macrophages and T cells and activate pain neurons directly and via activation of non-neuronal cells. It appears that enhanced expression of neuronal and glial TNF direct the development and the maintenance of neuropathic pain.

IL-17 is a major player in inflammation and a wide variety of autoimmune disorders. An increasing body of evidence indicates that IL-17 may also contribute to the development of neuropathic and spinal injury induced pain. Thus, IL-17A generates hyperexcitability of small to medium-sized dorsal root ganglion (DRG) neurons, implicating regulation of voltage-gated ion channels, and appears to include upregulated sensitivity of TRPV4 ion channels. Interestingly, IL-17 has also been implicated in fibromyalgia.

In the Molecular Medicine Reports study Caixia Sun and colleagues from the Jiangsu University Zhenjiang, China describe an infiltration with CD4+T cells in the spinal cord in a rat model of post-nerve injury. The authors identified CD4/IL‑17 positive cells located at the superficial laminae of the spinal dorsal horn.

These observations were associated with an up-regulation of IL‑17, IL‑1β and IL‑6 mRNA expression and high IL-17 protein levels in the spinal cord. Importantly, in vitro, IL‑17 stimulated resting astrocytes to produce IL-1β and IL-6 that may be linked to pain hypersensitivity.

The study suggests that IL-17 is involved in local activation of astrocytes and glial response that via the release of pro-inflammatory cytokine drives and maintains neuropathic pain.

Source: Mol Med Rep 2017 Jan 9;15(1):89-96. Epub 2016 Dec 9.
Read more:  Molecular Medicine Reports

Source: Cover Image: Profile of different cytokines in the generation of hyperalgesia. IL-17, IL-6, and TNF-α cause mechanical hyperalgesia, whereas thermal hyperalgesia is mainly induced by TNF-α and IL-1β. From Arthritis Res Ther. 2014; 16(5): 470, Hans-Georg Schaible; Open access, Public domain

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