Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain

Qin Zheng, Wenrui Xie, Debora D. Lückemeyer, Mark Lay, Xue Wei Wang, Xintong Dong, Nathachit Limjunyawong, Yaqing Ye, Feng Quan Zhou, Judith A. Strong, Jun Ming Zhang, Xinzhong Dong

Research output: Contribution to journalArticlepeer-review

Abstract

Spontaneous pain refers to pain occurring without external stimuli. It is a primary complaint in chronic pain conditions and remains difficult to treat. Moreover, the mechanisms underlying spontaneous pain remain poorly understood. Here we employed in vivo imaging of dorsal root ganglion (DRG) neurons and discovered a distinct form of abnormal spontaneous activity following peripheral nerve injury: clusters of adjacent DRG neurons firing synchronously and sporadically. The level of cluster firing correlated directly with nerve injury-induced spontaneous pain behaviors. Furthermore, we demonstrated that cluster firing is triggered by activity of sympathetic nerves, which sprout into DRGs after injury, and identified norepinephrine as a key neurotransmitter mediating this unique firing. Chemogenetic and pharmacological manipulations of sympathetic activity and norepinephrine receptors suggest that they are necessary and sufficient for DRG cluster firing and spontaneous pain behavior. Therefore, blocking sympathetically mediated cluster firing may be a new paradigm for treating spontaneous pain.

Original languageEnglish (US)
Pages (from-to)209-220.e6
JournalNeuron
Volume110
Issue number2
DOIs
StatePublished - Jan 19 2022

Keywords

  • DRG
  • adrenergic receptors
  • cluster firing
  • dorsal root ganglion neuron
  • neuropathic spontaneous pain
  • norepinephrine
  • sympathetic sprouting

ASJC Scopus subject areas

  • General Neuroscience

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