Electroacupuncture attenuates surgical pain-induced delirium-like behavior in mice via remodeling gut microbiota and dendritic spine

Abstract

Surgical pain is associated with delirium in patients, and acupuncture can treat pain. However, whether electroacupuncture can attenuate the surgical pain-associated delirium via the gut–brain axis remains unknown. Leveraging a mouse model of foot incision-induced surgical pain and delirium-like behavior, we found that electroacupuncture stimulation at specific acupoints (e.g., DU20+KI1) attenuated both surgical pain and delirium-like behavior in mice. Mechanistically, mice with incision-induced surgical pain and delirium-like behavior showed gut microbiota imbalance, microglia activation in the spinal cord, somatosensory cortex, and hippocampus, as well as an enhanced dendritic spine elimination in cortex revealed by two-photon imaging. The electroacupuncture regimen that alleviated surgical pain and delirium-like behavior in mice also effectively restored the gut microbiota balance, prevented the microglia activation, and reversed the dendritic spine elimination. These data demonstrated a potentially important gut–brain interactive mechanism underlying the surgical pain-induced delirium in mice. Pending further studies, these findings revealed a possible therapeutic approach in preventing and/or treating postoperative delirium by using perioperative electroacupuncture stimulation in patients.

Liraglutide ameliorates delirium-like behaviors of aged mice undergoing cardiac surgery by mitigating microglia activation via promoting mitophagy

“…A battery of behavioral tests was recently utilized to assess delirium-like behavior in a mouse model, facilitating preclinical delirium studies (Chen et al 2022 ; Yang et al 2022 ). We assessed mouse locomotor activity using the OFT and found significant impairment after cardiac surgery, in contrast to previous laparotomy-based studies (Li et al 2021 ).…”

Blood tau‐PT217 contributes to the anesthesia/surgery‐induced delirium‐like behavior in aged mice

“…Despite the need for an ideal animal model to study postoperative delirium‐like behavior, our lab has developed an animal behavioral test battery. This battery includes natural behaviors such as buried food and an open‐field test to evaluate attention and awareness, as well as a learned behavior test (Y maze) to assess cognition 54,56–58,78 . These tests evaluate behaviors in mice that rely on intact attention, organized thinking, and consciousness.…”

“…This battery includes natural behaviors such as buried food and an open-field test to evaluate attention and awareness, as well as a learned behavior test (Y maze) to assess cognition. 54,[56][57][58]78 These tests evaluate behaviors in mice that rely on intact attention, organized thinking, and consciousness. Notably, we have demonstrated that aged mice display greater susceptibility to these behaviors after anesthesia/surgery compared to adult mice, 56 which parallels the clinical observation of a higher incidence of postoperative delirium in senior patients relative to adult patients.…”

Advances in the prevention and treatment of postoperative delirium by acupuncture: A review

“…Animal studies have also confirmed that acupuncture can reduce cognitive impairment and the associated pathological changes after various types of surgery. Yang et al [ 47 ] found that EA stimulation at specific acupoints (e.g., DU20 + KI1) attenuated both surgical pain and delirium-like behavior in mice by a potentially important gut-brain interactive mechanism. Further studies showed that EA stimulation at specific acupoints could prevent neuroinflammation by reducing the activation of microglia at the spinal cord, somatosensory cortex, and hippocampus, and also affect the vagal-adrenal axis in mice.…”