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Precision medicine for diagnosing and treating neuropathic pain
A key protein that modulates axon regeneration can benefit patients

Neuropathic pain, characterised as a hypersensitive response to noxious and innocuous stimuli, is caused by a disease or lesion of the somatosensory nervous system. More than 385 million people worldwide are estimated to suffer from chronic neuropathic pain, which greatly impairs their quality of life, yet current analgesics are either nonspecific or insufficiently effective. This makes the proper diagnosis of the causes of pain and specific treatments for pain both necessary and highly important.

A team of researchers led by Dr Chih-Cheng Chen at Academia Sinica鈥檚 Institute of Biomedical Sciences, Taiwan, has made a major breakthrough by being the first to unveil a vital cytoskeleton protein called advillin, which can serve as a biomarker for diagnosing the causes of lesion, as well as a target to promote nerve regeneration and aid in the recovery of patients suffering neuropathic pain.

Advillin is a sensory neuron-specific protein that modulates axonal outgrowth. Dr Chen鈥檚 team discovered advillin expression in a specific subset of pain-sensing afferent neurons (nociceptors) that bind with isolectin B4 (IB4) and coordinate with focal adhesion components to fine-tune axon regeneration. The lack of advillin in pain-sensing neurons caused disturbances in axon outgrowth, with decreases in outgrowth velocity, branch number, and projection dynamics.

The team further established the link in mouse models. Eliminating or diminishing expressions of advillin in mouse models showed that proper and accurate nerve regeneration is crucial for recovery from neuropathic pain. Moreover, the team identified a novel cell behavior that advillin shed from axon terminals, detecting advillin protein in the cerebrospinal fluid in mice with painful peripheral neuropathy.

Their work reveals a key role for advillin in helping patients recover from forms of nerve damage, which is essential for resolving neuropathic pain. Advillin is thus a therapeutic target to promote precise axon regeneration and help patients cope with neuropathic pain, as well as a potential biomarker to diagnose peripheral painful neuropathy.

Their results were published on 15 August 2018 in PNAS.

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