Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model
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RESEARCH
Ketamine normalizes high‑gamma power in the anterior cingulate cortex in a rat chronic pain model Isabel D. Friesner1, Erik Martinez1, Haocheng Zhou1, Jonathan Douglas Gould3, Anna Li1, Zhe Sage Chen2,4,5 , Qiaosheng Zhang1*† and Jing Wang1,4,5*†
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. Keywords: Chronic pain, Anterior cingulate cortex, Ketamine, Gamma band power, Local field potential Introduction 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]. For example, there has been a dramatic rise in prescription of opioid drugs to treat chronic postoperative pain [3–5], which has in turn lead to sedation, respiratory depression, dependence and even addiction [5, 6]. Therefore, there is an urgent need not only to propel our understanding of the mechanism of chronic pain, but
*Correspondence: [email protected]; jing. [email protected] † Qiaosheng Zhang and Jing Wang contributed equally to this work 1 Department of Anesthesiology, Perioperative Care and Pain, New York University School of Medicine, New York, NY 10016, USA Full list of author information is available at the end of the article
also to find alternative effective analgesics with minimal side effects [7]. Recently, administrations of low, sub-anesthetic doses of ketamine either alone or as an adjunct to opioid therapies have been shown to be an effective treatment in postoperative and acute pain settings [8–12]. In addition, ketamine has long been safely used as an general anesthetic and analgesic agent [13]. Recently, the FDA approved a new intranasal preparation of ketamine for the treatment of acute depressive symptoms [14]. Specifically regarding chronic pain states, human and animal studies have shown the effectiveness of ketamine injections in
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