title: Biomarkers of neuropathic pain in skin nerve degeneration neuropathy: contact heat-evoked potentials as a physiological signature.
abstract: Contact heat-evoked potentials (CHEPs) have become an established method of assessing small-fiber sensory nerves; however, their potential as a physiological signature of neuropathic pain symptoms has not been fully explored. To investigate the diagnostic efficacy in examining small-fiber sensory nerve degeneration, the relationship with skin innervations, and clinical correlates with sensory symptoms, we recruited 188 patients (115 men) with length-dependent sensory symptoms and reduced intraepidermal nerve fiber (IENF) density at the distal leg to perform CHEP, quantitative sensory testing, and nerve conduction study. Fifty-seven age- and sex-matched controls were enrolled for comparison of CHEP and skin innervation. Among patients with neuropathy, 144 patients had neuropathic pain and 64 cases had evoked pain. Compared with quantitative sensory testing and nerve conduction study parameters, CHEP amplitudes showed the highest sensitivity for diagnosing small-fiber sensory nerve degeneration and exhibited the strongest correlation with IENF density in multiple linear regression. Contact heat-evoked potential amplitudes were strongly correlated with the degree of skin innervation in both patients with neuropathy and controls, and the slope of the regression line between CHEP amplitude and IENF density was higher in patients with neuropathy than in controls. Patients with evoked pain had higher CHEP amplitude than those without evoked pain, independent of IENF density. Receiver operating characteristic analysis showed that CHEP had better performance in diagnosing small-fiber sensory nerve degeneration than thermal thresholds. Furthermore, CHEPs showed superior classification accuracy with respect to evoked pain. In conclusion, CHEP is a sensitive tool to evaluate pathophysiology of small-fiber sensory nerve and serves as a physiological signature of neuropathic pain symptoms.
authors.affiliation: Departments of Neurology and.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Wu
authors.affiliation: Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Pathology, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Paul-Chen
authors.initials: PC
authors.lastname: Hsieh
authors.affiliation: Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Tseng
authors.affiliation: Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Chiang
authors.affiliation: Departments of Neurology and.
authors.forename: Chih-Pang
authors.initials: CP
authors.lastname: Chu
authors.affiliation: Departments of Neurology and.
authors.forename: Fang-Ping
authors.initials: FP
authors.lastname: Feng
authors.affiliation: Departments of Neurology and.
authors.forename: Yea-Huey
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Departments of Neurology and.|Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Anatomy and Cell Biology, National Taiwan University College of Medicine, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
authors.affiliation: Departments of Neurology and.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000150:complications*; D009412:Nerve Fibers; D009431:Neural Conduction / Q000502:physiology; D009437:Neuralgia / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D010812:Physical Stimulation; D012372:ROC Curve; D012867:Skin / Q000294:innervation*; D013624:Taiwan; D055815:Young Adult
chemical_list: D015415:Biomarkers