Chih-Cheng Chen, PhD, is a distinguished research fellow in the Institute of Biomedical Sciences, Academia Sinica, Taiwan. He received a PhD in Anatomy from the University College London, UK. After a postdoctoral fellowship with Dr. Andreas Zimmer and Michael Brownstein at NIH, he joined the faculty at the Academia Sinica, Taiwan. Dr. Chen's research focuses on the molecular and genetic controls of pain associated with tissue acidosis and neurosensory mechanotransduction. He initiated a new field of “sngception” to define the acidosis sensation in the somatosensory nervous system and distinguish it from nociception. He is also the director of Taiwan Mouse Clinic and the President of Taiwan Sng Society.
22 MARCH
| Time |
Session |
|
|
11:00
12:30
|
Diabetic Neuropathy: from Pathophysiology to Clinical Practice
-
Chih-Cheng ChenTaiwan
Speaker
Pathophysiological Mechanisms Underlying Diabetic NeuropathyDiabetic neuropathy is a prevalent complication of both type I and type II diabetes mellitus. However, although peripheral nerve degeneration is highly associated with painful neuropathy, the underlying mechanism remains largely unknown. Here we report a role of advillin in painful diabetic neuropathy in a mouse model of type I diabetes induced by multiple low doses of streptozotocin (STZ). Advillin is an actin-binding protein involved in regulating the organization of actin filaments and the dynamics of axonal growth cones. In mice, advillin is exclusively expressed in somatosensory neurons, ubiquitously expressed in all neuron subtypes during neonatal ages and particularly enriched in isolectin B4 positive (IB4+) non peptidergic neurons in adulthood. We previously showed that advillin plays a key role in axon regeneration of somatosensory neurons during peripheral neuropathy. Mice lacking advillin lost the ability to recover form neuropathic pain induced by oxaliplatin, chronic compression of sciatic nerve, and experimental autoimmune encephalitis. In the diabetic model, STZ-induced cold allodynia was resolved in 8 weeks in wild type (Avil+/+) mice, but could last more than 30 weeks in advillin-knockout (Avil-/-) mice. Additionally, Avil-/- but not Avil+/+ mice showed STZ-induced mechanical hypersensitivity of muscle. Consistent with the prolonged and/or worsened STZ-induced neuropathic pain, second-line coping responses to pain stimuli were greater in Avil-/- than in Avil+/+ mice. On analyzing intraepidermal nerve density, STZ induced large axon degeneration in the hind paws but with distinct patterns between Avil+/+ and Avil-/- mice. We next probed whether advillin knockout could disturb capsaicin induced axon regeneration ex vivo because capsaicin is clinically used to treat painful diabetic neuropathy by promoting axon regeneration. In a primary culture of dorsal root ganglion cells, 10 min capsaicin treatment selectively promoted neurite outgrowth of IB4+ neurons in Avil+/+ but not Avil-/- groups, which suggests that capsaicin could reprogram the intrinsic axonal regeneration by modulating the advillin-mediated actin dynamics. Together, advllin-dependent IB4+ axon regeneration plays an important role in the development of painful diabetic neuropathy.
-
Chi-Chao ChaoTaiwan
Speaker
Clinical Presentation and Diagnostic Evaluation of Diabetic NeuropathyDiabetic neuropathy (DN) is the most common microvascular complication of diabetes and a leading cause of peripheral neuropathy worldwide. With the global rise in diabetes prevalence, DN represents a growing clinical and public health challenge. Distal symmetric sensorimotor polyneuropathy (DSPN) is the predominant subtype, typically presenting with length-dependent sensory symptoms beginning in distal feet and progressing proximally. Patients commonly report various sensory symptoms like numbness, neuropathic pain, and imbalance. Although sensory manifestations predominate, motor weakness and autonomic dysfunction may occur and contribute to substantial morbidity, including foot ulceration, gait problem, cardiovascular and gastrointestinal complications.
The diagnosis of diabetic neuropathy requires compatible clinical symptoms and signs together with objective evidence of peripheral nerve dysfunction. Large-fiber involvement is assessed primarily by nerve conduction studies (NCS), which demonstrate reduced conduction velocity and action potential amplitudes in a length-dependent pattern. However, small-fiber neuropathy often occurs early and may precede detectable NCS abnormalities. Therefore, multimodal assessment is essential. Quantitative sensory testing (QST) allows functional evaluation of thermal (small-fiber) and vibratory (large-fiber) thresholds. Skin biopsy with intraepidermal nerve fiber density quantification provides morphologic confirmation of small-fiber degeneration. Corneal confocal microscopy offers a noninvasive surrogate marker of small-fiber integrity, while heat pain evoked potentials and autonomic function tests—including QSART and sudoscan—further characterize small-fiber and autonomic involvement. A comprehensive diagnostic approach integrating clinical evaluation with complementary large- and small-fiber testing improves diagnostic accuracy, enables earlier identification of high-risk individuals, and supports timely intervention to prevent disability.
This lecture reviews the clinical phenotypes, diagnostic criteria, and contemporary multimodal evaluation strategies for diabetic neuropathy, emphasizing the importance of early detection and precision phenotyping in clinical practice.
-
Yen-Feng Wang Taiwan
Speaker
Evidence-Based Management of Diabetic Neuropathy: Pharmacologic and Non-Pharmacologic Approaches
102
|
