Encoding of inflammatory hyperalgesia in mouse spinal cord

Omer Barkai, Prudhvi Raj Rayi, Rachely Butterman, Ben Katz, Shaya Lev, Alexander M. Binshtok*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Inflammation modifies the input-output properties of peripheral nociceptive neurons such that the same stimulus produces enhanced nociceptive firing. This increased nociceptive output enters the superficial dorsal spinal cord (SDH), an intricate neuronal network composed largely of excitatory and inhibitory interneurons and a small percentage of projection neurons. The SDH network comprises the first central nervous system network integrating noxious information. Using in vivo calcium imaging and a computational approach, we characterized the responsiveness of the SDH network in mice to noxious stimuli in normal conditions and investigated the changes in SDH response patterns after acute burn injury-induced inflammation. We show that the application of noxious heat stimuli to the hind paw of naïve mice results in an overall increase in SDH network activity. Single-cell response analysis reveals that 70% of recorded neurons increase or suppress their activity, while ∼30% of neurons remain nonresponsive. After acute burn injury and the development of inflammatory hyperalgesia, application of the same noxious heat stimuli leads to the activation of previously nonresponding neurons and desuppression of suppressed neurons. We further demonstrate that an increase in afferent activity mimics the response of the SDH network to noxious heat stimuli under inflammatory conditions. Using a computational model of the SDH network, we predict that the changes in SDH network activity result in overall increased activity of excitatory neurons, amplifying the output from SDH to higher brain centers. We suggest that during acute local peripheral inflammation, the SDH network undergoes dynamic changes promoting hyperalgesia.

Original languageAmerican English
Pages (from-to)443-460
Number of pages18
JournalPain
Volume164
Issue number2
DOIs
StatePublished - 1 Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

Keywords

  • Burn injury
  • In vivo two-photon imaging
  • Inflammatory hyperalgesia
  • Inflammatory pain
  • Spinal dorsal horn

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