Encoding of inflammatory hyperalgesia in mice spinal cord

Inflammation modifies the input-output properties of peripheral nociceptive neurons, thus leading to hyperalgesia, i.e., changes in the perception of noxious heat stimuli 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 the application of noxious heat stimuli to the mice hind paw in naive conditions 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 leads to activation of previously non-responded cells and de-suppression of the "suppressed" neurons. We demonstrate that reduction in synaptic inhibition mimics the response to the noxious stimuli in the hyperalgesic conditions. Using a computational model of SDH network, we predict that inflammation-induced "disinhibition"-like changes result in increased activity of excitatory projection neurons. Our model also predicts that the observed "disinhibitory" effect of hyperalgesic stimuli does not require changes in the inhibitory transmission and may result from the SDH networks9 intrinsic cytoarchitecture.