Neuropathic pain, characterized 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’s Institute of Biomedical Sciences 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. Their results were published in the August 15, 2018 issue of PNAS, and earned recognition as a high-impact article. The first author was Dr. Yu-chia Chuang, a graduate of Academia Sinica’s Taiwan International Graduate Program (TIGP) and Postdoctoral Research Fellow at the Institute of Biomedical Sciences. The team’s research was funded by the Ministry of Science & Technology (MOST) and Academia Sinica.
Advillin is a sensory neuron-specific protein that modulates axonal outgrowth. Dr. Chen’s 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. Dr. Chen’s team further established the link between advillin-mediated axon regeneration and neuropathic pain as demonstrated in mouse models of multiple sclerosis, including nerve damage caused by the chemotherapy drug oxaliplatin and sciatic nerve injury. 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.
The work of Dr. Chen’s team 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.
Full Article: http://www.pnas.org/content/early/2018/08/15/1716470115