Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice.

The hypothalamic supramammillary nucleus (SuM) plays a crucial role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find that approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from non-rapid-eye movement or rapid-eye movement sleep, and chemogenetic activation of SuMMS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for the modulation of wakefulness by this hypothalamic-septal projection.

Clinical Study on the Combination of Transcutaneous Electrical Acupoint Stimulation and Lidocaine for Preventing Propofol Injection Pain.

Purpose: Propofol is a widely used intravenous anesthetic in clinical practice. Lidocaine pretreatment is currently the most commonly used method to reduce the pain of propofol injection. However, propofol injection pain has not been eliminated and its incidence remains high. Transcutaneous electrical acupoint stimulation is a green therapy that combines transcutaneous electrical nerve stimulation therapy with the traditional acupuncture therapy of our motherland. This study investigated the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) combined with lidocaine in preventing propofol injection pain and determined whether it can reduce postoperative complications and promote rapid postoperative recovery of patients. Patients and Methods: A total of 220 women scheduled to undergo hysteroscopic surgery were enrolled in the study. The included patients were randomly divided into four groups of 55 patients each: normal saline group (group K), lidocaine group (group L), TEAS group (group T), and lidocaine + TEAS group (group L + T). Patients in group K received 2 mL saline (0.9% NaCl) pre-injection before anesthesia induction. Group L received 40 mg lidocaine pre-injection (2 mL of 2% lidocaine) before anesthesia induction. Group T received 30 min of transcutaneous electrical stimulation at bilateral election Hegu, Neiguan, and 2 mL saline pre-injections before anesthesia induction. Group L + T received TEAS and lidocaine pre-injection. Results: The VAS scores and the four-point verbal rating scale of propofol injection were significantly different among the four groups. The prevalence of nausea, vomiting, abdominal pain, and abdominal distension after surgery among the four groups were statistically different. The bleeding days after surgery were significantly different among the four groups. Conclusion: TEAS combined with lidocaine pre-injection reduced the incidence of propofol injection pain and significantly reduced patients' pain levels compared with single lidocaine pre-injection. TEAS can also reduce the incidence of postoperative nausea and vomiting, abdominal pain, and abdominal distension, shorten postoperative bleeding days, and accelerate the postoperative recovery of patients.

[Spinal transcription factor GATA4 mediated adenosine A1 receptor activation contributes to electroacupuncture analgesia in neuropathic pain rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on pain behaviors and expression of spinal transcription factor GATA-binding Protein 4 (GATA4) and adenosine A1 receptor in neuropathic pain rats, so as to explore its mechanism underlying pain relief. METHODS: The present study includes 2 parts. In the first part, 18 SD rats were randomly divided into control, adenovirus short-hairpin interference RNA for GATA4 (AV-shGATA4 RNA) and adenovirus empty vector (AV-control short-hairpin RNA, AV-shCTRL) groups, with 6 rats in each group. The expression of GATA4 protein in the lumbar spinal cord (L4-L6) was detected to evaluate the transfection efficiency of AV-shGATA4 RNA (silencing GATA4 expression). In the second part, thirty SD rats were randomly divided into 5 groups, namely sham operation, CCI model, EA, EA+AV-shGATA4 RNA, and EA+AV-shCTRL groups, with 6 rats in each group. The neuropathic pain model was established by chronic constriction injury (CCI) of the right sciatic nerve. On the 7th day following modeling, EA was applied to the right "Zusanli"(ST36) and "Taichong"(LR3) (1 mA，2 Hz /100 Hz) for 30 min. Rats of the EA+AV-shGATA4 RNA and EA+AV-shCTRL groups received intrathecal injection of AV-shGATA4 RNA and AV-shCTRL(1×1011 PFU/mL，10 µL)at the spinal L4-L6 segments, separately, 48 h before EA intervention. The mechanical pain threshold and thermal pain threshold of the affected limb were detected before molding, 7 days following molding and 60 min after EA. The expressions of adenosine A1 receptor and GATA4 protein in the spinal cord (L4-L6) were detected by Western blot. RESULTS: Outcomes of the first part showed that compared with the control group, no significant changes were found in the mechanical and thermal pain thresholds in both AV-shCTRL and AV-shGATA4 RNA groups and in the expression of spinal GATA4 protein of the AV-shCTRL group (P＞0.05). The expression of spinal GATA4 protein of the AV-shGATA4 RNA group was significantly lower than that of the AV-shCTRL group (P<0.05). In the second part of the study, before CCI modeling, there were no significant differences among the five groups in the mechanical and thermal pain thre-sholds (P> 0.05). On the 7th day following modeling, the mechanical and thermal pain thresholds were significantly lowered in compa-rison with their own pre-modeling of each group and with the sham operation group (P<0.05). At 60 min after EA and compared with the model group, the mechanical and thermal pain thresholds were significantly increased in both the EA and EA+AV-shCTRL groups (P<0.05) but not in the EA+AV-shGATA4 RNA group (P>0.05), suggesting a critical involvement of GATA4 in EA analgesia. The expression levels of adenosine A1 receptor and GATA4 protein were significantly increased in the model group than in the sham operation group (P<0.05), and considerably further up-regulated in both EA and EA+AV-shCTRL groups (P< 0.05), rather than in the EA+AV-shGATA4 RNA group (P>0.05), suggesting that the effects of EA in up-regulating the expression of A1 receptor and GATA4 were eliminated after silencing GATA4 protein. CONCLUSION: EA of ST36 and LR3 can relieve pain by increasing the expression of adenosine A1 receptor of the lumbar spinal cord in neuropathic pain rats, which is probably mediated by GATA4 protein.

[Effect of acupoint stimulation on the quality of recovery in patients with radical thyroidectomy under the concept of enhanced recovery after surgery: a randomized controlled trial].

OBJECTIVE: To observe the effect of acupoint stimulation on the quality of recovery in patients with radical thyroidectomy under the concept of enhanced recovery after surgery (ERAS). METHODS: A total of 62 patients with radical thyroidectomy were randomized into an observation group and a control group, 31 cases in each one. In both of the two groups, general anesthesia with tracheal intubation was applied, the same anesthesia induction and maintenance medication were given. In the observation group, auricular point pressing with magnetic beads was adopted at bilateral shenmen (TF4) and transcutaneous electrical acupoint stimulation (dilatational wave, 2 Hz/100 Hz in frequency, 6 to 12 mA) was performed at bilateral Hegu (LI 4) and Neiguan (PC 6) from 30 min before anesthesia induction to the end of the anesthesia. In the control group, medical adhesive plaster was pasted at bilateral shenmen (TF4) and the electrodes were plastered at bilateral Hegu (LI 4) and Neiguan (PC 6) with no corresponding stimulation. In both of the two groups, visual analogue scale for anxiety (VAS-A) score was observed to evaluate the anxiety severity before anesthesia induction; the total intraoperative dosages of sufentanil, remifentanil and propofol were recorded; the numerical rating scale (NRS) score was used to assess the pain severity of instant time (T0) and 30 min (T1) of entering post-anesthesia recovery room (PACU), motor and static mode at 2 h (T2), 6 h (T3), 12 h (T4), 24 h (T5) after surgery; time of first anal exhaust, time of getting out of bed after surgery, total hospitalization time and the incidences of postoperative nausea and vomiting were observed; the quality of recovery was assessed by the 40-item quality of recovery score (QoR-40). RESULTS: The VAS-A score and the total intraoperative dosage of remifentanil in the observation group were reduced compared with the control group (P<0.05). The NRS scores at T0-T4 in the observation group were lower than those in the control group (P<0.01, P<0.05), while the difference between the two groups in NRS score at T5 was not significant (P>0.05). The time of first anal exhaust and getting out of bed after surgery in the observation group were advanced than those in the control group (P<0.05), there was no significant difference between the two groups in total hospitalization time and incidences of postoperative nausea and vomiting (P>0.05). Compared with the control group, the QoR-40 score was increased in the observation group (P<0.05). CONCLUSION: Acupoint stimulation can improve the preoperative anxiety in patients with radical thyroidectomy, reduce the intraoperative anesthetic dosage and postoperative pain, advance the time of anal exhaust and getting out of bed, improve the quality of postoperative recovery and enhance the recovery process.

Multichannel fiber photometry for mapping axonal terminal activity in a restricted brain region in freely moving mice.

Fiber photometry has been increasingly popular in neuroscience research in freely behaving animals. In combination with genetically encoded calcium indicators, it allows for real-time monitoring of neural activity in neuronal somata, dendrites, and axonal terminals. We developed a multichannel fiber photometry device to map the activity of axonal terminals in a restricted, 100 - µ m -wide brain region in freely moving mice. This device consists of four bundled multimode fibers, each with a 50 - µ m core diameter and a scientific complementary metal-oxide semiconductor camera to simultaneously acquire fluorescence. We achieved a sampling rate of 100 frames / s and sufficient sensitivity to acquire data from axonal terminals. To avoid interference with neighboring channels, the recording depth of each channel was restricted to < 250 µ m . Furthermore, the small-core-diameter fibers did not restrict mouse locomotion. Using the Ca 2 + indicator GCaMP5G, we validated the system by recording Ca 2 + signals in axonal terminals from the medial entorhinal cortex layer II to the hippocampal dentate gyrus (DG) in freely moving mice. We detected spatially separated Ca 2 + signals at four different sites in the DG. Therefore, our multichannel fiber photometry device provides a simple but powerful method to functionally map axonal terminals in spatially confined brain areas of freely moving animals.

Effects of transcutaneous acupoint electrical stimulation combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus: A randomized controlled trial.

BACKGROUND: Myoclonus is an undesirable phenomenon that occurs after induction of general anesthesia using etomidate. Opioids such as sufentanil are considered effective pretreatment drugs for myoclonus inhibition, although high doses are required. Transcutaneous acupoint electrical stimulation (TAES), a noninvasive technique involving electrical stimulation of the skin at the acupuncture points, exhibits analgesic effects, promotes anesthetic effects, decreases the dose of anesthetic drugs, and increases endogenous opioid peptide levels. In the present study, we investigated the effects of TAES combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus in patients undergoing elective hysteroscopy. METHODS: In a double-blind manner, 172 patients (American Society of Anesthesiologists class I-II; age, 20-55 years) scheduled to undergo elective hysteroscopy were randomized into the following groups (n = 43 each): control (false TAES followed by saline injection after 30 min), TAES (TAES followed by saline injection after 30 minutes), sufentanil [false TAES followed by low-dose sufentanil (0.1 µg/kg) injection after 30 minutes], and sufentanil plus TAES (TAES followed by low-dose sufentanil injection after 30 minutes). In all groups, general anesthesia was induced by etomidate 0.3 mg/kg after sufentanil or saline injection. The incidence and severity of myoclonus were assessed for 2 minutes after etomidate administration. The visual analogue scale (VAS) scores for pain at 1 hour after surgery were recorded. The heart rate (HR), mean arterial pressure (MAP), and peripheral capillary oxygen saturation (SPO2) were recorded before premedication, after etomidate injection, after uterus expansion, and after recovery from anesthesia. RESULTS: The incidence of myoclonus was highest in the control group (88.3%), followed by TAES (74.4%), sufentanil (60.4%), and TAES plus sufentanil (48.8%) groups. Thus, the incidence was significantly higher in the control and TAES groups than in the sufentanil and TAES plus sufentanil groups. Grade 3 myoclonus occurred in 30.2%, 9.3%, 11.6%, and 9.3% patients in the control, TAES, sufentanil, and TAES plus sufentanil groups, respectively, with significant differences between the control group and the other 3 groups. Furthermore, the postoperative VAS scores for pain were significantly lower in the TAES, sufentanil, and TAES plus sufentanil groups compared with those in the control group. There were no significant differences in any other parameters among groups. CONCLUSION: Our results suggest that TAES combined with low-dose opioids such as sufentanil can decrease the incidence and severity of etomidate-induced myoclonus.

Locomotion-Related Population Cortical Ca2+ Transients in Freely Behaving Mice.

Locomotion involves complex neural activity throughout different cortical and subcortical networks. The primary motor cortex (M1) receives a variety of projections from different brain regions and is responsible for executing movements. The primary visual cortex (V1) receives external visual stimuli and plays an important role in guiding locomotion. Understanding how exactly the M1 and the V1 are involved in locomotion requires recording the neural activities in these areas in freely moving animals. Here, we used an optical fiber-based method for the real-time monitoring of neuronal population activities in freely moving mice. We combined the bulk loading of a synthetic Ca2+ indicator and the optical fiber-based Ca2+ recordings of neuronal activities. An optical fiber 200 µm in diameter can detect the coherent activity of a subpopulation of neurons. In layer 5 of the M1 and V1, we showed that population Ca2+ transients reliably occurred preceding the impending locomotion. Interestingly, the M1 Ca2+ transients started ~100 ms earlier than that in V1. Furthermore, the population Ca2+ transients were robustly correlated with head movements. Thus, our work provides a simple but efficient approach for monitoring the cortical Ca2+ activity of a local cluster of neurons during locomotion in freely moving animals.

[Efficacy observation on acupoint catgut embedding therapy combined medication for treatment of chronic urticaria induced by Helicobacter pylori infection].

OBJECTIVE: To observe the efficacy of acupoint catgut embedding therapy combined medication on chronic urticaria induced by Helicobacter pylori (HP) infection. METHODS: Ninety-two cases were randomly divided into 3 groups, named a medication group (group A, 31 cases), an acupoint catgut embedding group (group B, 30 cases) and a medication combined acupoint catgut embedding group (group C, 31 cases). In group A, the medication was administered orally for antihistamine and anti-HP infection. In group B, catgut embedding was applied on Quchi (LI 11), Xuehai (SP 10), Zusanli (ST 36), etc. In group C, acupoint catgut embedding therapy was applied in combination with medication (medication as group A, acupoint catgut embedding as group B). After 3-month treatment, the efficacy, recurrence rate and HP negative rate were compared among 3 groups. RESULTS: Separately, the effective rates of group A, B, C were 61.3% (19/31), 53.3% (16/30) and 90.3% (28/31); the recurrence rates were 27.3% (3/11), 33.3% (3/9) and 5.9% (1/17); and HP negative rates were 31.3% (10/31), 26.7% (9/30) and 77.4% (24/31). The clinical efficacy and HP negative rate in group C were superior to those in group A and B (P < 0.01, P < 0.05). CONCLUSION: Acupoint catgut embedding therapy combined medication is significant in efficacy and low in recurrence rate in treatment of chronic urticaria caused by HP infection.