Dr Sung-Tsang Hsieh’s Lab:

Neurobiology of Degeneration and Pain




Principle Investigator: Sung-Tsang Hsieh, MD, PhD

Attending Neurologist, Department of Neurology, National Taiwan University Hospital, Taipei, 100, Taiwan

Professor, Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, 100, Taiwan

Department of Anatomy and Cell Biology, RM#638, National Taiwan University College of Medicine, 1 Jen-Ai Road, Sec. 1, Taipei, 100, Taiwan

E-mail: shsieh@ ntu.edu.tw




PhD (Neuroscience), The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Master of Public Health (MPH, Environmental Health Sciences), Harvard University School of Public Health, Cambridge, Massachusetts, USA

MD, Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan


Professional Experience


Professor, Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan

Attending physician (Neurologist), Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Fellow, Department of Neurology, The Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA




2018  Jonathan Pembroke Award, International Peripheral Nerve Society, Baltimore, USA

2018  Outstanding Research Scholar, Ministry of Science and Technology, Executive Yuan, Taiwan Government

2016  Fellow, American Academy of Neurology

2015  Outstanding Research Scholar, Ministry of Science and Technology, Executive Yuan, Taiwan Government

2012  Outstanding Research Award, National Science Council, Executive Yuan, Taiwan Government

2010  Basic Research Award, Formosa Medical Association, Taipei, Taiwan

2009  Outstanding Research Award, National Science Council, Executive Yuan, Taiwan Government

2008  Distinguished Scholars Research Project, National Science Council, Executive Yuan, Taiwan Government

2008  Outstanding Teaching Award, National Taiwan University, Taipei, Taiwan

2005  Merck Sharp & Dohme Award, Taiwan Neurological Society

2003  Outstanding Teaching Award, National Taiwan University, Taipei, Taiwan

2003  Outstanding Research Award, National Science Council, Executive Yuan, Taiwan Government

2002  Teaching Award, The Foundation of Alumni, National Taiwan University College of Medicine in North American

2001  Medical Research Award, Professor W. Chen Foundation, Taipei, Taiwan

2000  Research Award, National Taiwan University College of Medicine, Taipei, Taiwan

1997  Teaching Award, National Taiwan University College of Medicine, Taipei, Taiwan

1995  Peter Lampert Young Investigator Award, Society of Experimental Neuropathology, Washington, D. C., USA



Skin innervation

Functional MRI

Contact heat evoked potential


Themes of research

Neurobiology of nerve degeneration and its consequences of neuropathic pain (peripheral and central mechanisms)

Skin biopsy to diagnose human neuropathy affecting small-diameter nociceptive nerves (small-fiber neuropathy, painful neuropathy)

Plasticity in neural circuitry of neuropathic pain

        Peripheral mechanisms: peripheral sensitization after nerve injury

Central mechanisms of neuropathic pain: changes in somatosensory pathways on functional magnetic resonance imaging (fMRI) and contact heat evoked potential (CHEP)

Diagnosis and therapy of peripheral neuropathy

Hereditary neuropathies: Characot-Marie-tooth disease (CMT), hereditary neuropathy with liability to pressure palsies (HNPP), familial amyloid polyneuropathy (FAP)

Inflammatory neuropathies: Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), Miller Fishere syndrome (MFS), neuropathies with anti-ganglioside antibodies



Our laboratory is devoted to investigate the neurobiological aspects of nerve degeneration and its consequences of neuroapthic pain, particularly focusing on small myelinated and unmyelinated nociceptive nerves (small-fibers) and their central pathways.  These nerve fibers terminate in the skin and are responsible for the transmission of thermal and nociceptive stimuli.  Previous studies were limited by their small diameter (usually 1-2 micrometers), and usually required electron microscopic examinations.  We have developed new techniques to investigate the nerve terminals in a global scale, and used these approaches to set up models of nerve terminal degeneration.  In addition to the loss of sensations, the other major consequence of nerve injury is neuropathic pain.  By applying the above approaches including neuroimaging (fMRI), physiology (CHEP), and molecular biology, we also established an integrated system of neuropathic pain.

A parallel focus in this laboratory is to use the previously described technique to diagnose human neuropathies involving small-diameter nociceptive nerves (small-fiber neuropathy).  This is quite a difficult issue for neurologists because there has been lack of objective methods to quantify the degeneration of small-fibers.  We are among the pioneers in this field to diagnose small-fiber fiber neuropathies in patients with inflammatory neuropathies and diabetes mellitus.

We have extended our laboratory services to the diagnosis and therapy of human neuropathies: (1) CMT, including peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), and connexin 32 and (2) FAP for the genetic mutations of transthyretin, the most common form of FAP.



1.      Chao CC, Hsueh HW, Kan HW, Liao CH, Jiang HH, Chiang H, Lin WM, Yeh TY, Lin YH, Cheng YY et al. Skin nerve pathology: biomarkers of premanifest and manifest amyloid neuropathy. Ann Neurol 2019; 85:560-573.

2.      Kan HW, Hsieh JH, Chien HF, Lin YH, Yeh TY, Chao CC, Hsieh ST. CD40-mediated HIF-1a expression underlying microangiopathy in diabetic nerve pathology. Dis Models Mech 2018; 11:4.

3.      Kan HW, Chiang H, Lin WM, Yu I, Lin SW, Hsieh ST. Sensory nerve degeneration in a mouse model mimicking early manifestations of familial amyloid polyneuropathy due to transthyretin Ala97Ser. Neuropathol Appl Neurobiol 2018; 44:673-686.

4.      Hsieh YL, Kan HW, Chiang H, Lee YC, Hsieh ST. Distinct TrkA and Ret modulated negative and positive neuropathic behaviors in a mouse model of resiniferatoxin-induced small fiber neuropathy. Exp Neurol 2018; 300:87-99.

5.      Wu SW, Wang YC, Hsieh PC, Tseng MT, Chiang MC, Chu CP, Feng FP, Lin YH, Hsieh ST, Chao CC. Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature. Pain 2017; 158:516-525.

6.      Chang MF, Hsieh JH, Chiang H, Kan HW, Huang CM, Chellis L, Lin BS, Miaw SC, Pan CL, Chao CC et al. Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection. Sci Rep 2016; 6:35612.

7.      Chao CC, Huang CM, Chiang HH, Luo KR, Kan HW, Yang NC-C, Chiang H, Lin WM, Lai SM, Lee MJ et al. Sudomotor innervation in transthyretin amyloid neuropathy: pathology and functional correlates. Ann Neurol 2015; 78:272-283.

8.      Chiang H, Ohno N, Hsieh YL, Mahad DJ, Kikuchi S, Komuro H, Hsieh ST, Trapp BD. Mitochondrial fission augments capsaicin-induced axonal degeneration. Acta Neuropathol 2015; 129:81-96.

9.      Hsieh PC, Tseng MT, Chao CC, Lin YH, Tseng WY, Liu KH, Chiang MC, Hsieh ST. Imaging signatures of altered brain responses in small-fiber neuropathy: reduced functional connectivity of the limbic system after peripheral nerve degeneration. Pain 2015; 156:904-916.

10.  Tseng MT, Kong Y, Chiang MC, Chao CC, Tseng WY, Hsieh ST. Brain imaging signatures of the relationship between epidermal nerve fibers and heat pain perception. NeuroImage 2015; 122:288-297.

11.  Lin MT, Lee LJH, Chao CC, Hsieh ST. Quality of life in polyneuropathy: association with biomarkers of small fiber impairment. Health Qual Life Outcomes 2015; 13:169.

12.  Hsieh JH, Lin WM, Chiang H, Chang LY, Wu CT, Pu CM, Wu JT, Hsieh ST. Patterns of target tissue reinnervation and trophic factor expression after nerve grafting. Plast Reconstr Surg 2013; 131:989-1000.

13.  Tseng MT, Chiang MC, Chao CC, Tseng WY, Hsieh ST. fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations. Hum Brain Mapp 2013; 34:2733-2746.

14.  Tseng MT, Chiang MC, Yazhuo K, Chao CC, Tseng WY, Hsieh ST. Effect of aging on the cerebral processing of thermal pain in the human brain. Pain 2013; 154:2120-2129.

15.  Luo KR, Chao CC, Hsieh PC, Hsieh ST. Effect of glycemic control on sudomotor denervation in type 2 diabetes. Diabetes Care 2012; 35:612-616.

16.  Hsieh YL, Chiang H, Lue JH, Hsieh ST. P2X3-mediated peripheral sensitization of neuropathic pain in resiniferatoxin-induced neuropathy. Exp Neurol 2012; 235:316-325.

17.  Chao CC, Wu VC, Tan CH, Wang YM, Li H, Tseng MT, Wu PC, Lin YH, Lin WM, Wu KD et al. Skin denervation and its clinical significance in late-stage chronic kidney disease. Arch Neurol 2011; 68:200-206.

18.  Luo KR, Chao CC, Chen YT, Huang CM, Yang NC, Kan HW, Wang SH, Yang WS, Hsieh ST. Quantitation of sudomotor innervation on skin biopsies in diabetic neuropathy. J Neuropathol Exp Neurol 2011; 70:930-938.

19.  Chao CC, Tseng MT, Lin YJ, Yang WS, Hsieh SC, Lin YH, Chiu MJ, Chang YC, Hsieh ST. Pathophysiology of neuropathic pain in type 2 diabetes: skin denervation and contact heat evoked potentials. Diabetes Care 2010; 33:2654-2659.

20.  Yang NC, Lee MJ, Chao CC, Chuang YT, Lin WM, Chang MF, Hsieh PC, Kan HW, Lin YH, Yang CC et al. Clinical presentations and skin denervation in amyloid neuropathy due to transthyretin Ala97Ser. Neurology 2010; 75:532-538.

21.  Tseng MT, Tseng WY, Chao CC, Lin HE, Hsieh ST. Distinct and shared cerebral activations in processing innocuous versus noxious contact heat revealed by functional magnetic resonance imaging. Hum Brain Mapp 2010; 31:743-757.

22.  Hsieh YL, Lin WM, Lue JH, Chang MF, Hsieh ST. Effects of 4-methylcatechol on skin reinnervation: promotion of cutaneous nerve regeneration after crushing injury. J Neuropathol Exp Neurol 2009; 68:1269-1281.

23.  Chao CC, Hsieh SC, Tseng MT, Chang YC, Hsieh ST. Patterns of contact heat evoked potential (CHEP) in neuropathy with skin denervation: correlation of CHEP amplitude with intraepidermal nerve fiber density. Clin Neurophysiol 2008; 119:653-661.

24.  Chao CC, Sun HY, Chang YC, Hsieh ST. Painful neuropathy with skin denervation after prolonged use of linezolid. J Neurol Neurosurg Psychiatry 2008; 79:97-99.

25.  Hsieh YL, Chiang H, Tseng TJ, Hsieh ST. Enhancement of cutaneous nerve regeneration by 4-methylcatechol in resiniferatoxin-induced neuropathy. J Neuropathol Exp Neurol 2008; 67:93-104.

26.  Lin YY, Tseng TJ, Hsieh YL, Luo KR, Lin WM, Chiang H, Hsieh ST. Depletion of peptidergic innervation in the gastric mucosa of streptozotocin-induced diabetic rats. Exp Neurol 2008; 213:388-396.

27.  Tseng TJ, Chen CC, Hsieh YL, Hsieh ST. Influences of surgical decompression on the dorsal horn after chronic constriction injury: changes in peptidergic and d-opioid receptor (+) nerve terminals. Neuroscience 2008; 156:758-768.

28.  Chao CC, Hsieh ST, Chiu MJ, Tseng MT, Chang YC. Effects of aging on contact heat evoked potentials: the physiological assessment of thermal perception. Muscle Nerve 2007; 36:30-38.

29.  Tseng TJ, Chen CC, Hsieh YL, Hsieh ST. Effects of decompression on neuropathic pain behaviors and skin reinnervation in chronic constriction injury. Exp Neurol 2007; 204:574-582.

30.  Chao CC, Hsieh ST, Shun CT, Hsieh SC. Skin denervation and cutaneous vasculitis in eosinophilia-associated neuropathy. Arch Neurol 2007; 64:959-965.

31.  Chao CC, Hsieh SC, Yang WS, Lin YH, Lin WM, Tai TY, Hsieh ST. Glycemic control is related to the severity of impaired thermal sensations in type 2 diabetes. Diabetes Metab Res Rev 2007; 23:612-620.

32.  Tseng MT, Hsieh SC, Shun CT, Lee KL, Pan CL, Lin WM, Lin YH, Yu CL, Hsieh ST. Skin denervation and cutaneous vasculitis in systemic lupus erythematosus. Brain 2006; 129:977-985.

33.  Lin CY, Su YN, Lee CN, Hung CC, Cheng WF, Lin WL, Chen CA, Hsieh ST. A rapid and reliable detection system for the analysis of PMP22 gene dosage by MP/DHPLC assay. J Hum Genet 2006; 51:227-235.

34.  Chiang HY, Chen CT, Chien HF, Hsieh ST. Skin denervation, neuropathology, and neuropathic pain in a laser-induced focal neuropathy. Neurobiol Dis 2005; 18:40-53.

35.  Chiang HY, Chien HF, Shen HH, Yang JD, Chen YH, Chen JH, Hsieh ST. Reinnervation of muscular targets by nerve regeneration through guidance conduits. J Neuropathol Exp Neurol 2005; 64:576-587.

36.  Lee JE, Shun CT, Hsieh SC, Hsieh ST. Skin denervation in vasculitic neuropathy. Arch Neurol 2005; 62:1570-1573.

37.  Lin YH, Hsieh SC, Chao CC, Chang YC, Hsieh ST. Influence of aging on thermal and vibratory thresholds of quantitative sensory testing. J Peripher Nerv Syst 2005; 10:269-281.

38.  Chang YC, Lin WM, Hsieh ST. Effects of aging on human skin innervation. NeuroReport 2004; 15:149-153.

39.  Hsieh ST, Chu NS. Immunohistochemical study of skin nerve regeneration after toe-to-finger transplantation: correlations with clinical, quantitative sensory, and electrophysiological evaluations. Acta Neurol Taiwan 2004; 13:178-185.

40.  Hsu SH, Lee MJ, Hsieh SC, Scaravilli F, Hsieh ST. Cutaneous and sympathetic denervation in neonatal rats with a mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4) gene. Neurobiol Dis 2004; 16:335-345.

41.  Pan CL, Shun CT, Susuki K, Yuki K, Hsieh ST. Pharyngeal-brachial palsy after cytomegalovirus colitis. Neurology 2004; 62:153-154.

42.  Shun CT, Chang YC, Wu HP, Hsieh SC, Lin WM, Lin YH, Tai TY, Hsieh ST. Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments. Brain 2004; 127:1593-1605.

43.  Pan CL, Tseng TJ, Lin YH, Chiang MC, Lin WM, Hsieh ST. Cutaneous innervation in Guillain-Barre syndrome: pathology and clinical correlations. Brain 2003; 126:386-397.

44.  Chiang MC, Lin YH, Pan CL, Tseng TJ, Lin WM, Hsieh ST. Cutaneous innervation in chronic inflammatory demyelinating polyneuropathy. Neurology 2002; 59:1094-1098.

45.  Ko MH, Chen WP, Hsieh ST. Neuropathology of skin denervation in acrylamide-induced neuropathy. Neurobiol Dis 2002; 11:155-165.

46.  Chien HF, Tseng TJ, Lin WM, Yang CC, Chang YC, Chen RC, Hsieh ST. Quantitative pathology of cutaneous nerve terminal degeneration in the human skin. Acta Neuropathol 2001; 102:455-461.


Book Chapter

Hsieh ST. Toxic neuropathies. In Schmidt RF and Willis WD, editors. Encyclopedia of Pain. Berlin, Germany: Springer-Verlag, 2013.


Small fiber neuropathy and related syndromes: neurodegeneration and pain. Editor-in-Chief: Hsieh ST; Co-editors: Anand P, Gibbons C, and Sommer C. Springer-Nature, Singapore, 2019.