Towards bridging the translational gap by improved modeling of human nociception in health and disease

Pflugers Arch. 2022 Sep;474(9):965-978. doi: 10.1007/s00424-022-02707-6. Epub 2022 Jun 3.

Abstract

Despite numerous studies which have explored the pathogenesis of pain disorders in preclinical models, there is a pronounced translational gap, which is at least partially caused by differences between the human and rodent nociceptive system. An elegant way to bridge this divide is the exploitation of human-induced pluripotent stem cell (iPSC) reprogramming into human iPSC-derived nociceptors (iDNs). Several protocols were developed and optimized to model nociceptive processes in health and disease. Here we provide an overview of the different approaches and summarize the knowledge obtained from such models on pain pathologies associated with monogenetic sensory disorders so far. In addition, novel perspectives offered by increasing the complexity of the model systems further to better reflect the natural environment of nociceptive neurons by involving other cell types in 3D model systems are described.

Keywords: Inflammatory pain; Monogenetic pain disorders; Neuropathic pain; Pathological pain; mRNA; microRNA.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Nociception*
  • Nociceptors / metabolism
  • Pain / metabolism