title: Pathophysiology of neuropathic pain in type 2 diabetes: skin denervation and contact heat-evoked potentials.
abstract: OBJECTIVE
  Neuropathic pain due to small-fiber sensory neuropathy in type 2 diabetes can be diagnosed by skin biopsy with quantification of intra-epidermal nerve fiber (IENF) density. There is, however, a lack of noninvasive physiological assessment. Contact heat-evoked potential (CHEP) is a newly developed approach to record cerebral responses of Aδ fiber-mediated thermonociceptive stimuli. We investigated the diagnostic role of CHEP.
  
  
  METHODS
  From 2006 to 2009, there were 32 type 2 diabetic patients (20 males and 12 females, aged 51.63 ± 10.93 years) with skin denervation and neuropathic pain. CHEPs were recorded with heat stimulations at the distal leg, where skin biopsy was performed.
  
  
  RESULTS
  CHEP amplitude was reduced in patients compared with age- and sex-matched control subjects (14.8 ± 15.6 vs. 33.7 ± 10.1 μV, P < 0.001). Abnormal CHEP patterns (reduced amplitude or prolonged latency) were noted in 81.3% of these patients. The CHEP amplitude was the most significant parameter correlated with IENF density (P = 0.003) and pain perception to contact heat stimuli (P = 0.019) on multiple linear regression models. An excitability index was derived by calculating the ratio of the CHEP amplitude over the IENF density. This excitability index was higher in diabetic patients than in control subjects (P = 0.023), indicating enhanced brain activities in neuropathic pain. Among different neuropathic pain symptoms, the subgroup with evoked pain had higher CHEP amplitudes than the subgroup without evoked pain (P = 0.011).
  
  
  CONCLUSIONS
  CHEP offers a noninvasive approach to evaluate the degeneration of thermonociceptive nerves in diabetic neuropathy by providing physiological correlates of skin denervation and neuropathic pain.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chao
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Tseng
authors.forename: Ya-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Wei-Shiung
authors.initials: WS
authors.lastname: Yang
authors.forename: Song-Chou
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Yea-Huey
authors.initials: YH
authors.lastname: Lin
authors.forename: Ming-Jang
authors.initials: MJ
authors.lastname: Chiu
authors.forename: Yang-Chyuan
authors.initials: YC
authors.lastname: Chang
authors.forename: Sung-Tsang
authors.initials: ST
authors.lastname: Hsieh
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000503:physiopathology*; D012867:Skin / Q000294:innervation*; D055815:Young Adult