British journal of anaesthesia · 2025
Cerebellar vermis and somatosensory-motor cortex differentially contribute to sex differences in acute pain perception in rats.
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Liu Xingxing, Sun Ran, Zhang Kun, Xie Xiaoyu, Wu Xia, Zheng Bingwen, Guo Yingkun, Zhang Lizhi, Zhang Wensheng
Аннотация
BACKGROUND: Pain is a universal experience, yet sex differences in acute pain perception remain unclear. Here, we examined sex-specific brain responses to acute pain evoked by tail clamping in rats.
METHODS: A suitable isoflurane concentration for resting-state functional magnetic resonance imaging (rs-fMRI) was identified to ensure sedation without suppressing nociceptive responsiveness. rs-fMRI was performed to assess sex differences in brain activity and functional connectivity during acute pain, with control groups receiving touch stimulation or isoflurane-only exposure to identify pain-specific activation. The fMRI findings were validated using immunofluorescence staining of sex-specifically activated brain regions and spinal cord and corresponding dorsal root ganglia.
RESULTS: Acute pain significantly altered brain functional networks in both sexes. Female rats exhibited increased brain activity in the left cerebellar vermis, whereas males showed higher activity in the left secondary motor cortex (M2), extending into the left hindlimb (S1HL) and barrel field (S1BF) regions of the primary somatosensory cortex, a pattern distinct from non-nociceptive conditions. Functional connectivity revealed weak connections between the cerebellar vermis and somatosensory-motor cortex (M2, S1HL, and S1BF) in both sexes. Within the somatosensory-motor cortex, females showed strongest connectivity between S1HL and M2 (R=0.66), whereas males showed it between S1HL and S1BF (R=0.87). Immunostaining confirmed increased c-Fos and Egr-1 expression in sex-specific activated brain regions and in the spinal cord and dorsal root ganglion.
CONCLUSIONS: Differences in the activity and functional connectivity of the cerebellar vermis and somatosensory-motor cortex appear to contribute to sex differences in pain perception in rodents.
METHODS: A suitable isoflurane concentration for resting-state functional magnetic resonance imaging (rs-fMRI) was identified to ensure sedation without suppressing nociceptive responsiveness. rs-fMRI was performed to assess sex differences in brain activity and functional connectivity during acute pain, with control groups receiving touch stimulation or isoflurane-only exposure to identify pain-specific activation. The fMRI findings were validated using immunofluorescence staining of sex-specifically activated brain regions and spinal cord and corresponding dorsal root ganglia.
RESULTS: Acute pain significantly altered brain functional networks in both sexes. Female rats exhibited increased brain activity in the left cerebellar vermis, whereas males showed higher activity in the left secondary motor cortex (M2), extending into the left hindlimb (S1HL) and barrel field (S1BF) regions of the primary somatosensory cortex, a pattern distinct from non-nociceptive conditions. Functional connectivity revealed weak connections between the cerebellar vermis and somatosensory-motor cortex (M2, S1HL, and S1BF) in both sexes. Within the somatosensory-motor cortex, females showed strongest connectivity between S1HL and M2 (R=0.66), whereas males showed it between S1HL and S1BF (R=0.87). Immunostaining confirmed increased c-Fos and Egr-1 expression in sex-specific activated brain regions and in the spinal cord and dorsal root ganglion.
CONCLUSIONS: Differences in the activity and functional connectivity of the cerebellar vermis and somatosensory-motor cortex appear to contribute to sex differences in pain perception in rodents.