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Neuropathic pain correlates with myelinated fiber loss and cytokine profile in POEMS syndrome
  1. Haruki Koike (harukikoike99{at}yahoo.co.jp)
  1. Nagoya University Graduate School of Medicine, Japan
    1. Masahiro iijima
    1. Nagoya University Graduate School of Medicine, Japan
      1. Keiko Mori
      1. Nagoya University Graduate School of Medicine, Japan
        1. Masahiko Yamamoto
        1. Aichi Gakuin University School of Health Science, Japan
          1. Naoki Hattori
          1. Nagoya University Graduate School of Medicine, Japan
            1. Hirohisa Watanabe
            1. Nagoya University Graduate School of Medicine, Japan
              1. Fumiaki Tanaka
              1. Nagoya University Graduate School of Medicine, Japan
                1. Manabu Doyu
                1. Aichi Medical University, Japan
                  1. Gen Sobue (sobueg{at}med.nagoya-u.ac.jp)
                  1. Nagoya University Graduate School of Medicine, Japan

                    Abstract

                    Objective: To reveal characteristic clinicopathologic 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 histopathologic 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 fiber population using complete transverse sural nerve cross-sections, excluding the marked enlargement of endoneurial areas due to intrafascicular edema, showed that myelinated fibers, especially small myelinated fibers, were reduced, while unmyelinated fibers were preserved. Uncompacted myelin lamellae and segmental demyelination were seen more frequently in the small rather than the large myelinated fibers. 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 fiber loss (p < 0.01). Serum levels of proinflammatory cytokines (interleukin-1β, interleukin-6, and tumor necrosis factor-á), but not their soluble receptors, were significantly elevated in patients with hyperalgesia (p <0.05-0.01).

                    Conclusions: Hyperalgesia seen in POEMS syndrome patients is closely related to a reduction in the myelinated, but not unmyelinated, fiber population. Elevation of proinflammatory cytokines is also correlated with hyperalgesia. The painful symptoms in POEMS syndrome may be generated by well-preserved unmyelinated C-fibers due to the lack of inhibitory myelinated A-fibers along with cytokine sensitization.

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