behavior/neurological
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• under physiological conditions, mice exhibit normal basal pain sensitivity with no significant alterations in touch sensation (adhesive removal test), nociceptive responses to deep mechanical stimuli (Randall-Selitto test), reflex behavior to heat at 48-, 50-, and 52 degrees C (tail flick test), response to heat at 50-, 53- and 56 degrees C (hot plate test), and acute pain behavior after intraplantar formalin injection (formalin test)
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• following intraplantar injection of Complete Freunds Adjuvant (CFA) to induce persistent inflammatory pain, mice exhibit decreased mechanical allodynia in response to stimulation with von Frey filaments, with significantly higher paw withdrawal thresholds at 1-, 3- and 7 days after CFA injection than wild-type controls
• however, CFA-injected mice show normal heat hyperalgesia and cold allodynia as assayed by Hargreaves and acetone tests, respectively
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• following tibial neuroma transposition (TNT) surgery, a model of chronic post-amputation pain, mice show decreased phantom limb pain in response to stimulation with von Frey filaments, with significantly higher paw withdrawal thresholds at day 3 and day 14 post-surgery than wild-type controls
• moreover, TNT-operated mice show decreased residual stump pain with a significantly lower response frequency to stimulation with 0.16g filaments at all time points between days 3 and 14 post-surgery, consistent with decreased mechanical allodynia
• however, TNT-operated mice show normal heat hyperalgesia and cold allodynia as assayed by Hargreaves and acetone tests, respectively
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immune system
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• following TNT surgery, mice show a significant reduction in both macrophage density (CD68+ cell number/mm2) and macrophage area (CD68+ signal area %) in the dorsal root ganglion (DRG)
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• following TNT surgery, mice show a significant reduction in macrophage infiltration and expression of the pro-inflammatory cytokines Il1b (interleukin 1 beta) and Tnf (tumor necrosis factor) in the dorsal root ganglion (DRG) while expression of ATF3 (a nerve injury marker) is not altered, suggesting an anti-inflammatory effect
• however, TNT-operated mice show no significant change in macrophage infiltration in the residual tibial nerve stump
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hematopoietic system
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• following TNT surgery, mice show a significant reduction in both macrophage density (CD68+ cell number/mm2) and macrophage area (CD68+ signal area %) in the dorsal root ganglion (DRG)
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