Demise of nociceptive Schwann cells causes nerve retraction and pain hyperalgesia

Puneet Rinwa, Laura Calvo-Enrique, Ming-Dong Zhang, Jens Randel Nyengaard, Páll Karlsson, Patrik Ernfors

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46 Citations (Scopus)
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Abstract

Recent findings indicate that nociceptive nerves are not "free", but similar to touch and pressure sensitive nerves, terminate in an end-organ in mice. This sensory structure consists of the nociceptive nerves and specialized nociceptive Schwann cells forming a mesh-like organ in subepidermis with pain transduction initiated at both these cellular constituents. The intimate relation of nociceptive nerves with nociceptive Schwann cells in mice raises the question whether defects in nociceptive Schwann cells can by itself contribute to pain hyperalgesia, nerve retraction, and peripheral neuropathy. We therefore examined the existence of nociceptive Schwann cells in human skin and their possible contribution to neuropathy and pain hyperalgesia in mouse models. Similar to mouse, human skin contains SOX10 +/S100B +/AQP1 +Schwann cells in the subepidermal border that have extensive processes, which are intimately associated with nociceptive nerves projecting into epidermis. The ablation of nociceptive Schwann cells in mice resulted in nerve retraction and mechanical, cold, and heat hyperalgesia. Conversely, ablating the nociceptive nerves led to a retraction of epidermal Schwann cell processes, changes in nociceptive Schwann cell soma morphology, heat analgesia, and mechanical hyperalgesia. Our results provide evidence for a nociceptive sensory end-organ in the human skin and using animal models highlight the interdependence of the nerve and the nociceptive Schwann cell. Finally, we show that demise of nociceptive Schwann cells is sufficient to cause neuropathic-like pain in the mouse.

Original languageEnglish
JournalPain
Volume162
Issue6
Pages (from-to)1816-1827
Number of pages12
ISSN0304-3959
DOIs
Publication statusPublished - 1 Jun 2021

Keywords

  • Nerve retraction
  • Nociceptive Schwann cells
  • Pain hyperalgesia
  • Peripheral neuropathy

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