Hedging against Neuropathic Pain: Role of Hedgehog Signaling in Pathological Nerve Healing

Int J Mol Sci. 2020 Nov 30;21(23):9115. doi: 10.3390/ijms21239115.

Abstract

The peripheral nervous system has important regenerative capacities that regulate and restore peripheral nerve homeostasis. Following peripheral nerve injury, the nerve undergoes a highly regulated degeneration and regeneration process called Wallerian degeneration, where numerous cell populations interact to allow proper nerve healing. Recent studies have evidenced the prominent role of morphogenetic Hedgehog signaling pathway and its main effectors, Sonic Hedgehog (SHH) and Desert Hedgehog (DHH) in the regenerative drive following nerve injury. Furthermore, dysfunctional regeneration and/or dysfunctional Hedgehog signaling participate in the development of chronic neuropathic pain that sometimes accompanies nerve healing in the clinical context. Understanding the implications of this key signaling pathway could provide exciting new perspectives for future research on peripheral nerve healing.

Keywords: desert hedgehog; nerve healing; neuropathic pain; peripheral nerve injury; sonic hedgehog.

Publication types

  • Review

MeSH terms

  • Disease Management
  • Disease Susceptibility*
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Homeostasis
  • Humans
  • Morphogenesis
  • Nerve Regeneration
  • Neuralgia / etiology*
  • Neuralgia / metabolism*
  • Neuralgia / therapy
  • Pain Management
  • Peripheral Nerve Injuries / etiology
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / physiopathology
  • Peripheral Nerve Injuries / therapy
  • Peripheral Nerves / embryology
  • Peripheral Nerves / growth & development
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology
  • Signal Transduction*
  • Wound Healing / drug effects

Substances

  • Hedgehog Proteins