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.
Highlights
Chronic pain impacts around 20% of people globally [1]
Multi-channel local field potentials (LFPs) data were collected over multiple sessions, each consisting of continuous recordings over at least 30 noxious pinprick stimulations to the rat’s hind paw, contralateral to the anterior cingulate cortex (ACC) tetrode implants, though a mesh table (Fig. 1a)
This study is aimed at investigating LFP responses in the ACC to noxious stimulations in the chronic pain state and the effect of ketamine on these responses
Summary
Chronic pain impacts around 20% of people globally [1]. Current treatments cause many side effects due to the incomplete understanding of the mechanisms of chronic pain [2]. Regarding chronic pain states, human and animal studies have shown the effectiveness of ketamine injections in eliciting a rapid response to peripheral nociceptive inputs, and in some cases, showing sustained analgesic efficacy lasting up to a week [15,16,17,18]. These fact-acting and persistent effects of ketamine prompt further investigation into its analgesic mechanisms
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