Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model

Abstract

Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood at the network level. In this study, we recorded local field potentials from the ACC of freely moving rats. Animals were injected with complete Freund’s adjuvant (CFA) to induce persistent inflammatory pain. Mechanical stimulations were administered to the hind paw before and after CFA administration. We found a significant increase in the high-gamma band (60–100 Hz) power in response to evoked pain after CFA treatment. Ketamine, however, reduced the high-gamma band power in response to evoked pain in CFA-treated rats. In addition, ketamine had a sustained effect on the high-gamma band power lasting up to five days after a single dose administration. These results demonstrate that ketamine has the potential to alter maladaptive neural responses in the ACC induced by chronic pain.

Changes in alpha, theta, and gamma oscillations in distinct cortical areas are associated with altered acute pain responses in chronic low back pain patients

“…Scientifically, peripheral and spinal mechanisms as well as mechanisms in the brain may contribute to hypersensitivity at the site of injury, whereas the brain likely plays a more dominant role in a more generalized form of hyperalgesia. Our results here are compatible with findings from multiple animal studies that specifically investigated hyperalgesia of diffuse distribution, where enhancement in high gamma oscillatory activities in the ACC has been shown to be important and likely play a causal role (Zhang et al, 2017;Friesner et al, 2020;Sun et al, 2021). The dlPFC, meanwhile, is known to produce top-down pain regulation, and its activation in response to nociceptive inputs has been widely reported in both human and animal literature (Hardy, 1985;Lee et al, 2015;Zhang et al, 2015;Kiritoshi et al, 2016;Martinez et al, 2017;Dale et al, 2018).…”

Translational Applications of Neuroimaging

“…Scientifically, peripheral and spinal mechanisms as well as mechanisms in the brain may contribute to hypersensitivity at the site of injury, whereas the brain likely plays a more dominant role in a more generalized form of hyperalgesia. Our results here are compatible with findings from multiple animal studies that specifically investigated hyperalgesia of diffuse distribution, where enhancement in high gamma oscillatory activities in the ACC has been shown to be important and likely play a causal role Friesner et al, 2020;Sun et al, 2021). The dlPFC, meanwhile, is known to produce top-down pain regulation, and its activation in response to nociceptive inputs has been widely reported in both human and animal literature (Hardy, 1985;Kiritoshi et al, 2016;Martinez et al, 2017;Dale et al, 2018).…”

Combined Transcriptomic and Proteomic Profiling of the Mouse Anterior Cingulate Cortex Identifies Potential Therapeutic Targets for Pulpitis-Induced Pain

“…Currently, the mechanisms underlying pulpitis-induced pain were primarily at the peripheral level, with limited research on central mechanisms. ,− , While it is known that ACC was activated during pain, − ,, its involvement in pulpitis-induced pain remained unclear. To address these gaps, we conducted transcriptomic and proteomic analyses and verified the key DEGs and DEPs by qRT-PCR in the ACC of pulpitis models.…”

“…Among them, ACC plays an important role in pain sensation and pain-related affective emotions. Neurons in ACC were activated in acute and chronic pain. − However, whether ACC is involved in pulpitis-induced pain remains unknown.…”