Effect of transcranial direct current stimulation on postoperative sleep disturbance in older patients undergoing lower limb major arthroplasty: a prospective, double-blind, pilot, randomised controlled trial.

Background: Postoperative sleep disturbance (PSD) is a common and serious postoperative complication and is associated with poor postoperative outcomes. Aims: This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on PSD in older patients undergoing lower limb major arthroplasty. Methods: In this prospective, double-blind, pilot, randomised, sham-controlled trial, patients 65 years and over undergoing lower limb major arthroplasty were randomly assigned to receive active tDCS (a-tDCS) or sham tDCS (s-tDCS). The primary outcomes were the objective sleep measures on postoperative nights (N) 1 and N2. Results: 116 inpatients were assessed for eligibility, and a total of 92 patients were enrolled; 47 received a-tDCS and 45 received s-tDCS. tDCS improved PSD by altering the following sleep measures in the a-tDCS and s-tDCS groups; the respective comparisons were as follows: the promotion of rapid eye movement (REM) sleep time on N1 (64.5 (33.5-105.5) vs 19.0 (0.0, 45.0) min, F=20.10, p<0.001) and N2 (75.0 (36.0-120.8) vs 30.0 (1.3-59.3) min, F=12.55, p<0.001); the total sleep time on N1 (506.0 (408.0-561.0) vs 392.0 (243.0-483.5) min, F=14.13, p<0.001) and N2 (488.5 (455.5-548.5) vs 346.0 (286.5-517.5) min, F=7.36, p=0.007); the deep sleep time on N1 (130.0 (103.3-177.0) vs 42.5 (9.8-100.8) min, F=24.4, p<0.001) and N2 (103.5 (46.0-154.8) vs 57.5 (23.3-106.5) min, F=8.4, p=0.004); and the percentages of light sleep and REM sleep on N1 and N2 (p<0.05 for each). The postoperative depression and anxiety scores did not differ significantly between the two groups. No significant adverse events were reported. Conclusion: In older patients undergoing lower limb major arthroplasty, a single session of anodal tDCS over the left dorsolateral prefrontal cortex showed a potentially prophylactic effect in improving postoperative short-term objective sleep measures. However, this benefit was temporary and was not maintained over time.

Transcranial Direct Current Stimulation for Anxiety During Laparoscopic Colorectal Cancer Surgery: A Randomized Clinical Trial.

Importance: Perioperative anxiety is prevalent among patients undergoing surgical treatment of cancer and often influences their prognosis. Transcranial direct current stimulation (tDCS) has shown potential in the treatment of various anxiety-related disorders, but data on the impact of tDCS on perioperative anxiety are limited. Objective: To evaluate the effect of tDCS in reducing perioperative anxiety among patients undergoing laparoscopic colorectal cancer (CRC) resection. Design, Setting, And Participants: This randomized clinical trial was conducted from March to August 2023 at the Affiliated Hospital of Xuzhou Medical University. Patients aged 18 years or older undergoing elective laparoscopic radical resection for CRC were randomly assigned to either the active tDCS group or the sham tDCS group. Intention-to-treat data analysis was performed in September 2023. Interventions: Patients were randomly assigned to receive 2 sessions of either active tDCS or sham tDCS over the left dorsolateral prefrontal cortex on the afternoon of the day before the operation and in the morning of the day of operation. Main Outcomes and Measures: The main outcome was the incidence of perioperative anxiety from the day of the operation up to 3 days after the procedure, as measured using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) subscale (range: 0-21, with higher scores indicating more anxiety). Secondary outcomes included postoperative delirium (assessed by the Confusion Assessment Method or Confusion Assessment Method intensive care unit scale); pain (assessed by the 10-point Numeric Rating Scale [NRS], with scores ranging from 0 [no pain] to 10 [worst pain]); frailty (assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of Weight [FRAIL] Index, with scores ranging from 0 [most robust] to 5 [most frail]; and sleep quality (assessed by the Pittsburgh Sleep Quality Index [PSQI], with scores ranging from 0 to 21 and higher scores indicating worse sleep quality) after the 2 sessions of the tDCS intervention. Results: A total of 196 patients (mean [SD] age, 63.5 [11.0] years; 124 [63.3%] men) were recruited and randomly assigned to the active tDCS group (98 patients) or the sham tDCS group (98 patients). After the second tDCS intervention on the day of the operation, the incidence of perioperative anxiety was 38.8% in the active tDCS group and 70.4% in the sham tDCS group (relative risk, 0.55 [95% CI, 0.42-0.73]; P < .001). Patients in the active tDCS group vs the sham tDCS group were less likely to have postoperative delirium (8.2% vs 25.5%) and, at 3 days after the operation, had lower median (IQR) pain scores (NRS, 1.0 [1.0-1.0] vs 2.0 [2.0-2.0]), better median (IQR) sleep quality scores (PSQI, 10.5 [10.0-11.0] vs 12.0 [11.0-13.0]), and lower median (IQR) FRAIL Index (2.0 [1.0-2.0] vs 2.0 [2.0-3.0]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that administration of 2 preoperative sessions of tDCS was associated with a decreased incidence of perioperative anxiety in patients undergoing elective CRC resection. Active tDCS was also associated with better anxiety scores, pain levels, and sleep quality as well as reduced postoperative delirium and frailty. The findings suggest that tDCS may be a novel strategy for improving perioperative anxiety in patients undergoing CRC resection. Trial Registration: Chinese Clinical Trial Register Identifier: ChiCTR2300068859.

CRF regulates pain sensation by enhancement of corticoaccumbal excitatory synaptic transmission.

Both peripheral and central corticotropin-releasing factor (CRF) systems have been implicated in regulating pain sensation. However, compared with the peripheral, the mechanisms underlying central CRF system in pain modulation have not yet been elucidated, especially at the neural circuit level. The corticoaccumbal circuit, a structure rich in CRF receptors and CRF-positive neurons, plays an important role in behavioral responses to stressors including nociceptive stimuli. The present study was designed to investigate whether and how CRF signaling in this circuit regulated pain sensation under physiological and pathological pain conditions. Our studies employed the viral tracing and circuit-, and cell-specific electrophysiological methods to label the CRF-containing circuit from the medial prefrontal cortex to the nucleus accumbens shell (mPFCCRF-NAcS) and record its neuronal propriety. Combining optogenetic and chemogenetic manipulation, neuropharmacological methods, and behavioral tests, we were able to precisely manipulate this circuit and depict its role in regulation of pain sensation. The current study found that the CRF signaling in the NAc shell (NAcS), but not NAc core, was necessary and sufficient for the regulation of pain sensation under physiological and pathological pain conditions. This process was involved in the CRF-mediated enhancement of excitatory synaptic transmission in the NAcS. Furthermore, we demonstrated that the mPFCCRF neurons monosynaptically connected with the NAcS neurons. Chronic pain increased the protein level of CRF in NAcS, and then maintained the persistent NAcS neuronal hyperactivity through enhancement of this monosynaptic excitatory connection, and thus sustained chronic pain behavior. These findings reveal a novel cell- and circuit-based mechanistic link between chronic pain and the mPFCCRF → NAcS circuit and provide a potential new therapeutic target for chronic pain.

Efficacy of transcranial direct current stimulation for improving postoperative quality of recovery in elderly patients undergoing lower limb major arthroplasty: a randomized controlled substudy.

Background: Previous studies have demonstrated improvements in motor, behavioral, and emotional areas following transcranial direct current stimulation (tDCS), but no published studies have reported the efficacy of tDCS on postoperative recovery quality in patients undergoing lower limb major arthroplasty. We hypothesized that tDCS might improve postoperative recovery quality in elderly patients undergoing lower limb major arthroplasty. Methods: Ninety-six patients (≥65 years) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to receive 2 mA tDCS for 20 min active-tDCS or sham-tDCS. The primary outcome was the 15-item quality of recovery (QoR-15) score on postoperative day one (Т2). Secondary outcomes included the QoR-15 scores at the 2nd hour (T1), the 1st month (Т3), and the 3rd month (Т4) postoperatively, numeric rating scale scores, and fatigue severity scale scores. Results: Ninety-six elderly patients (mean age, 71 years; 68.7% woman) were analyzed. Higher QoR-15 scores were found in the active-tDCS group at T2 (123.0 [114.3, 127.0] vs. 109.0 [99.3, 115.3]; median difference, 13.0; 95% CI, 8.0 to 17.0; p < 0.001). QoR-15 scores in the active-tDCS group were higher at T1 (p < 0.001), T3 (p = 0.001), and T4 (p = 0.001). The pain scores in the active-tDCS group were lower (p < 0.001 at motion; p < 0.001 at rest). The fatigue degree scores were lower in the active-tDCS group at T1 and T2 (p < 0.001 for each). Conclusion: tDCS may help improve the quality of early recovery in elderly patients undergoing lower limb major arthroplasty. Clinical trial registration: The trial was registered at the China Clinical Trial Center (ChiCTR2200057777, https://www.chictr.org.cn/showproj.html?proj=162744).

Efficacy of transcranial direct current stimulation on postoperative delirium in elderly patients undergoing lower limb major arthroplasty: A randomized controlled trial.

BACKGROUND: Postoperative delirium (POD) is a common and severe postoperative complication in elderly patients undergoing major surgery linked to increased morbidity and mortality. It is reported that transcranial direct current stimulation (tDCS) effectively enhances cognitive function and improves impaired consciousness. OBJECTIVE: This study aimed to evaluate the efficacy of tDCS on POD in elderly patients undergoing lower limb major arthroplasty, including total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: Patients aged ≥65 years scheduled for THA or TKA were randomly assigned to receive 2 mA tDCS for 20 min active-tDCS (n = 61) or sham-tDCS (n = 61). The primary outcome was the incidence of POD during the first 3 postoperative days. RESULTS: All 122 patients (median age, 70 years; 80 women [65.6%]) completed the trial. The incident delirium risk was 4.9% (n = 3) vs. 19.7% (n = 12) in active-tDCS and sham-tDCS groups, respectively (relative risk, 0.250; 95% CI, 0.074 to 0.842; P = 0.013). Compared to the sham-tDCS group, the anxiety and depression scores of patients in the active-tDCS group were lower at 2 h and one day after surgery (P < 0.001 for each), and pain scores of patients in the active-tDCS group were lower during the first three days after surgery (P < 0.05). CONCLUSION: One session of anodal tDCS over the left dorsolateral prefrontal cortex may decrease the incidence of POD in elderly patients undergoing lower limb major arthroplasty.

Transcranial Electrical Stimulation for Relief of Peripartum Mental Health Disorders in Women Undergoing Cesarean Section With Combined Spinal-Epidural Anesthesia: A Pilot Randomized Clinical Trial.

Objective: This study aimed to explore transcranial electrical stimulation (tES) to relieve peripartum anxiety and depressive symptoms in women undergoing cesarean section with combined spinal-epidural anesthesia. Methods: This double-blind, randomized, sham-controlled trial was conducted in the Affiliated Hospital of Xuzhou Medical University from March 2021 and May 2021. One hundred and forty-eight full-term parturients giving birth by elective cesarean section were selected, and 126 were included in the intent-to-treat analysis. Parturients were provided standardized anesthesia and randomized to the active-tES (a-tES) group and sham-tES group. Parturients and outcome assessors were blinded to treatment allocation. The primary outcome was the changes in peripartum mental health disorders, including anxiety, assessed by the Pregnancy-Related Anxiety Questionnaire-Revised 2 (PRAQ-R2). Secondary outcomes included peripartum depressive symptoms, assessed by the Edinburgh Postnatal Depression Scale (EPDS), maternal satisfaction, fatigue level, sleep quality index, and pain score during and after operation. Data were collected before entering the operating room (T0), between post-anesthesia and pre-surgery (T1), before leaving the operating room (T2), and at 24 h post-surgery (T3). Results: One hundred and twenty-six eligible parturients were enrolled in the two groups: a-tES group (N = 62) and sham-tES group (N = 64). Treatment with tES resulted in significantly lower scores of anxiety compared with sham-tES (T2: P < 0.001; T3: P = 0.001). Moreover, the a-tES groups showed a significant reduction in depression scores (T2: P = 0.003; T3: P = 0.032). Conclusion: In this randomized pilot study, tES treatment is efficacious in alleviating peripartum anxiety and depressive symptoms in women undergoing cesarean section and has been demonstrated to be a novel strategy for improving peripartum mental health disorders. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR2000040963].