Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia

Kieran A. Boyle, Mark A. Gradwell, Toshiharu Yasaka, Allen C. Dickie, E. Polgár, Robert P. Ganley, Desmond P.H. Orr, Masahiko Watanabe, Victoria E. Abraira, Emily D. Kuehn, Amanda L. Zimmerman, David D. Ginty, Robert J. Callister, Brett A. Graham, David I. Hughes

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I–IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain. In this study, Boyle et al. identify parvalbumin-expressing spinal interneurons as a principal source of axoaxonic synapses onto cutaneous myelinated afferents and inhibitory inputs onto lamina II vertical cells. Following peripheral nerve injury, disinhibition of these targets facilitates the aberrant recruitment of pain circuits, leading to tactile allodynia.

Original languageEnglish (US)
Pages (from-to)526-540.e6
JournalCell Reports
Volume28
Issue number2
DOIs
StatePublished - Jul 9 2019

Keywords

  • LTMRs
  • allodynia
  • dorsal horn
  • interneurons
  • parvalbumin
  • presynaptic inhibition
  • touch

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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