Extended Data Fig. 5: Impact of cued fear conditioning on nociceptive and tactile sensitivity and prefrontal basis of interplay between fear and pain.
From: Prefrontal engrams of long-term fear memory perpetuate pain perception
(a) Impact of fear conditioning on paw withdrawal responses to graded mechanical von Frey force across noxious and non-noxious intensities in naïve mice (baseline); n = 16 mice/group. (b) Impact of fear conditioning on withdrawal responses to von Frey hairs after nerve injury; shown are data from the ipsilateral paw; n = 8 mice/group. (c) Impact of fear conditioning on withdrawal responses to thermal nociceptive stimuli (Hargreaves plantar test) in baseline condition and longitudinally after induction of unilateral paw inflammation (CFA); shown are data from the ipsilateral paw; n = 6 mice/group. In all panels, two-way ANOVA with Tukey’s multiple comparisons test was performed. (d) Experimental scheme for labelling prefrontal long-term fear memory engram and testing its overlap with prefrontal neurons responsive to a heat ramp or tactile von Frey stimulation in baseline conditions and changes thereof after induction of paw inflammation (CFA) or nerve injury (SNI). (e) Typical examples fear engram-labelled neurons (Venus) and overlap (arrows) with neurons activated by light touch or heat (Fos+Venus); the expression was verified and quantified in n = 4 mice in the Sham group and n = 4 mice in the SNI group; scale bars represent 50 µm; n.s.: non-significant. Data are shown as mean + /− S.E.M. All p and F values are shown in Supplementary Table 1.
