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bioRxiv · 10.1101/2021.05.18.444665

Encoding of inflammatory hyperalgesia in mice spinal cord

Barkai, O.·Butterman, R.·Katz, B.·Lev, S.·Binshtok, A. M.
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Abstract

Inflammation modifies the input-output properties of peripheral nociceptive neurons, thus leading to hyperalgesia, a condition in which the perception of noxious heat stimuli is altered such that the same stimulus produces enhanced pain. The increased nociceptive output enters the superficial dorsal spinal cord (SDH), which comprises the first CNS network integrating the noxious information. Here we used in vivo calcium imaging and a computational approach to investigate how the SDH network in mice encodes the injury-mediated abnormal input from peripheral nociceptive neurons. We show that the application of noxious heat stimuli to the hind paw in naive mice before induction of injury affects the activity of 70% of recorded neurons by either increasing or suppressing it. Application of the same noxious heat stimuli to hyperalgesic skin following injury leads to activation of previously non-responded cells and de-suppression of the "suppressed" neurons. We further demonstrate that reduction in synaptic inhibition mimics the response to the noxious stimuli in hyperalgesic conditions. Using a computational model of the SDH network, we predict that the "disinhibitory" effect of hyperalgesic stimuli results from the inflammation-mediated increased afferent input to the SDH network and a decrease in SDH inhibition. Both of these processes synergistically contribute to the injury-mediated increase in SDH output towards higher brain centers.

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Barkai, O., Butterman, R., Katz, B., Lev, S., Binshtok, A. M.. 2021-05-18. Encoding of inflammatory hyperalgesia in mice spinal cord. https://doi.org/10.1101/2021.05.18.444665

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