Leaky Gate Model: Intensity-Dependent Coding of Pain and Itch in the Spinal Cord

Shuohao Sun, Qian Xu, Changxiong Guo, Yun Guan, Qin Liu, Xinzhong Dong

Research output: Contribution to journalArticlepeer-review

Abstract

Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity, and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin-releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. When activated, these Grp+ neurons generated rarely seen, simultaneous robust pain and itch responses that were intensity dependent. Accordingly, we propose a “leaky gate” model in which Grp+ neurons transmit both itch and weak pain signals; however, upon strong painful stimuli, the recruitment of endogenous opioids works to close this gate, reducing overwhelming pain generated by parallel pathways. Consistent with our model, loss of these Grp+ neurons increased pain responses while itch was decreased. Our new model serves as an example of non-monotonic coding in the spinal cord and better explains observations in human psychophysical studies.

Original languageEnglish (US)
Pages (from-to)840-853.e5
JournalNeuron
Volume93
Issue number4
DOIs
StatePublished - Feb 22 2017

Keywords

  • gate control, Grp neuron
  • itch
  • leaky gate
  • neural circuit
  • pain
  • spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

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