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. 2023 Apr 18;120(17):e2211631120. doi: 10.1073/pnas.2211631120

Fig. 1.

Fig. 1.

A hyperalgesic priming model for widespread pain in mice. (A) Schematic for study design: a hyperalgesic priming model of chronic widespread pain was induced in mice using intramuscular injections of carrageenan on D0 and D4 in primed mice (n = 7). Control mice (n = 7) received a single intramuscular injection on D0. After D29, cells and serum were obtained following cardiac bleed from primed and control mice and injected into recipient naïve mice whose pain behavior was monitored up to 7 d. (B, i) Mechanical hypersensitivity to von Frey stimulation of ipsilateral and contralateral limbs in primed mice (red) and control mice (**P < 0.01, ***P < 0.001 two-way RM ANOVA primed ipsilateral vs. control ipsilateral; xx P < 0.01, xxx P < 0.001 two way RM ANOVA primed contralateral vs. control contralateral). (B, ii) Area under the curve of mechanical pain thresholds illustrated in (B, i) of ipsilateral and contralateral hindlimbs in primed ‘P’ and control ‘C’ mice (*P < 0.05, **P < 0.01 unpaired t test). (C) Weightbearing asymmetry of hind limbs (*P < 0.05, ***P < 0.001 two-way RM ANOVA primed vs. control). (D) Latency to nociceptive behavior in the hot plate assay (two-way RM ANOVA primed vs. control). (E) Latency to nociceptive withdrawal in Hargreaves’ assay (two-way RM ANOVA primed ipsilateral vs. control ipsilateral, primed contralateral vs. control contralateral). (F) Evoked action potential firing of neurons in the (i–v) ipsilateral dorsal horn (control cells n = 37, n = 42 primed cells) and in the (vi–x) contralateral deep dorsal horn (control cells n = 27, n = 44 primed cells) of primed mice and control mice to (i and vi) innocuous brush stimulation, (ii and vii) von Frey stimuli, (iii and viii) noxious prod stimulation, (iv and ix) heat stimuli, and (v and x) noxious cold stimulation with ethyl chloride (*P < 0.05, **P < 0.01 unpaired t test). (G) Mechanical hypersensitivity following adoptive transfer of blood cells from primed mice (n = 4) and control mice (n = 4) with timecourse shown in (i) and area under the curve analysis of timecourse compared in (ii) (*P < 0.05 unpaired t test). (H) Mechanical hypersensitivity of naïve mice following adoptive transfer of blood serum from primed mice (n = 4) and control mice (n = 4) with timecourse shown in (i) and area under the curve analysis of timecourse compared in (ii) (unpaired t test).