Pain and Itch Processing in Aged Mice

Most reports agree that aging negatively impacts pain processing and that the prevalence of chronic pain increases significantly with age. To improve current therapies, it is critical that aged animals be included in preclinical studies. Here we compared sensitivities to pain and itch-provoking stimuli in naive and injured young and aged mice. Surprisingly, we found that in the absence of injury, aged male and female mice are significantly less responsive to mechanical stimuli and, in females, also to noxious thermal (heat) stimuli. In both older male and female mice, compared to younger (6-month-old mice), we also recorded reduced pruritogen-evoked scratching. On the other hand, after nerve injury, aged mice nevertheless developed significant mechanical hypersensitivity. Interestingly, however, and in contrast to young mice, aged mice developed both ipsilateral and contralateral postinjury mechanical allodynia. In a parallel immunohistochemical analysis of micro-glial and astrocyte markers, we found that the ipsilateral to the contralateral ratio of nerve injury-induced expression decreased with age. That observation is consistent with our finding of con-tralateral hypersensitivity after nerve injury in the aged but not the young mice. We conclude that aging has opposite effects on baseline versus postinjury pain and itch processing. Perspective: Aged male and female mice (22-24 months) are less sensitive to mechanical, thermal (heat), and itch-provoking stimuli than are younger mice (6 months).(R) 2023 The Author(s). Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).