title: Neuropathic pain correlates with myelinated fibre loss and cytokine profile in POEMS syndrome.
abstract: OBJECTIVE
  To reveal characteristic clinicopathological correlates of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome.
  
  
  METHODS
  The clinical features of 22 patients with POEMS syndrome were investigated and correlated with the histopathological features of sural nerves and serum cytokine profiles.
  
  
  RESULTS
  More than half of the patients complained of pain in the lower extremities, which is closely related to hyperalgesia. Assessment of the total nerve fibre population using complete transverse sural nerve cross-sections, excluding the marked enlargement of endoneurial areas due to intrafascicular oedema, showed that myelinated fibres, especially small myelinated fibres, were reduced, whereas unmyelinated fibres were preserved. Uncompacted myelin lamellae and segmental demyelination were seen more frequently in the small, rather than the large, myelinated fibres. The presence of hyperalgesia was electrophysiologically associated with a reduction of sensory nerve action potentials in the sural nerve (p<0.05) and histopathologically associated with myelinated fibre loss (p<0.01). Serum levels of proinflammatory cytokines (interleukin-1beta, interleukin-6 and tumour necrosis factor-alpha), but not their soluble receptors, were significantly elevated in patients with hyperalgesia (p<0.05-0.01).
  
  
  CONCLUSIONS
  Hyperalgesia seen in patients with POEMS syndrome is closely related with a reduction in the myelinated, but not unmyelinated, fibre population. Elevation of proinflammatory cytokines is also correlated with hyperalgesia. The painful symptoms in POEMS syndrome may be generated by well-preserved unmyelinated C-fibres due to the lack of inhibitory myelinated A-fibres, along with cytokine sensitisation.
authors: Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan .
authors: H
authors: H
authors: Koike
authors: M
authors: M
authors: Iijima
authors: K
authors: K
authors: Mori
authors: M
authors: M
authors: Yamamoto
authors: N
authors: N
authors: Hattori
authors: H
authors: H
authors: Watanabe
authors: F
authors: F
authors: Tanaka
authors: M
authors: M
authors: Doyu
authors: G
authors: G
authors: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000276:immunology* / Q000473:pathology*; D009431:Neural Conduction / Q000502:physiology; D009437:Neuralgia / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D016878:POEMS Syndrome / Q000175:diagnosis* / Q000276:immunology* / Q000503:physiopathology; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000276:immunology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha