Adult brain activation in response to pain is changed by neonatal painful stimulation according to sex: A manganese‐enhanced MRI study

Abstract

Although it is known that nociceptive stimulation in the first postnatal week in rats is useful to model preterm pain, resulting in activation of specific brain areas, as assessed in vivo using manganese‐enhanced magnetic resonance imaging (MEMRI), little is known about its long‐term effects and sex specificity. Here we aimed to investigate whether inflammatory pain induced in male and female adult rats modify the pattern of brain activation between animals subjected or not to neonatal pain. For this, Complete Freund's adjuvant (CFA) was injected into the left hind paw of rat pups on postnatal day 1 (P1) or P8 to induce inflammatory response. During adulthood, CFA‐treated and control animals were injected with CFA 1 hr prior MRI. MEMRI has the ability to enhance the contrast of selective brain structures in response to a specific stimulus, as the pain. MEMRI responses were consistent with activation of nociceptive pathways and these responses were reduced in animals treated with CFA on P1, but increased in animals treated on P8, mainly in the female group. In agreement, P8 female group showed exacerbated responses in the thermal nociceptive test. Using MEMRI, we conclude that the natural ability of adult rats to recognize and react to pain exposition is modified by neonatal painful exposition, mainly among females.

Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI

“…This activation pattern is reminiscent to what has been described in a previous study investigating acute inflammatory pain in male and female rats. Using manganese-enhanced MRI, the authors found increased activation of S1, M1, CPu and amygdala in female compared to male rats (Malheiros et al, 2021). Moreover, investigating muscle and cutaneous pain in humans, Henderson and colleagues found increased activation of mid-cingulate cortex and dorsolateral PFC in naïve female compared to male human volunteers, while the overall pain intensity rating was not affected (Henderson et al, 2008).…”