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 naïve 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 microglial 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 contralateral 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).

Paradoxical increases in anterior cingulate cortex activity during nitrous oxide-induced analgesia reveal a signature of pain affect.

The general consensus is that increases in neuronal activity in the anterior cingulate cortex (ACC) contribute to pain's negative affect. Here, using in vivo imaging of neuronal calcium dynamics in mice, we report that nitrous oxide, a general anesthetic that reduces pain affect, paradoxically, increases ACC spontaneous activity. As expected, a noxious stimulus also increased ACC activity. However, as nitrous oxide increases baseline activity, the relative change in activity from pre-stimulus baseline was significantly less than the change in the absence of the general anesthetic. We suggest that this relative change in activity represents a neural signature of the affective pain experience. Furthermore, this signature of pain persists under general anesthesia induced by isoflurane, at concentrations in which the mouse is unresponsive. We suggest that this signature underlies the phenomenon of connected consciousness, in which use of the isolated forelimb technique revealed that pain percepts can persist in anesthetized patients.