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.

GABAergic Neurons in the Dorsal-Intermediate Lateral Septum Regulate Sleep-Wakefulness and Anesthesia in Mice.

BACKGROUND: The γ-aminobutyric acid-mediated (GABAergic) inhibitory system in the brain is critical for regulation of sleep-wake and general anesthesia. The lateral septum contains mainly GABAergic neurons, being cytoarchitectonically divided into the dorsal, intermediate, and ventral parts. This study hypothesized that GABAergic neurons of the lateral septum participate in the control of wakefulness and promote recovery from anesthesia. METHODS: By employing fiber photometry, chemogenetic and optogenetic neuronal manipulations, anterograde tracing, in vivo electrophysiology, and electroencephalogram/electromyography recordings in adult male mice, the authors measured the role of lateral septum GABAergic neurons to the control of sleep-wake transition and anesthesia emergence and the corresponding neuron circuits in arousal and emergence control. RESULTS: The GABAergic neurons of the lateral septum exhibited high activities during the awake state by in vivo fiber photometry recordings (awake vs. non-rapid eye movement sleep: 3.3 ± 1.4% vs. -1.3 ± 1.2%, P < 0.001, n = 7 mice/group; awake vs. anesthesia: 2.6 ± 1.2% vs. -1.3 ± 0.8%, P < 0.001, n = 7 mice/group). Using chemogenetic stimulation of lateral septum GABAergic neurons resulted in a 100.5% increase in wakefulness and a 51.2% reduction in non-rapid eye movement sleep. Optogenetic activation of these GABAergic neurons promoted wakefulness from sleep (median [25th, 75th percentiles]: 153.0 [115.9, 179.7] s to 4.0 [3.4, 4.6] s, P = 0.009, n = 5 mice/group) and accelerated emergence from isoflurane anesthesia (514.4 ± 122.2 s vs. 226.5 ± 53.3 s, P < 0.001, n = 8 mice/group). Furthermore, the authors demonstrated that the lateral septum GABAergic neurons send 70.7% (228 of 323 cells) of monosynaptic projections to the ventral tegmental area GABAergic neurons, preferentially inhibiting their activities and thus regulating wakefulness and isoflurane anesthesia depth. CONCLUSIONS: The results uncover a fundamental role of the lateral septum GABAergic neurons and their circuit in maintaining awake state and promoting general anesthesia emergence time.

KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice.

Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

[Body Image and Its Clinical Implications].

Although the concept of body image was first introduced to Taiwan nursing in 1975, its application in the context of clinical nursing with regard to promoting humanistic patient-centered care has yet to be examined. This paper adopts a field-study approach to reinterpret the concept of body image with deeper and broader strength using patient vignettes, nursing case studies, and the findings of prior nursing research. The four main issues covered in this paper are: 1. The body image concept, 2. Building body schema and a postural model based on body experiences, 3. The characteristics of body image, and 4. The extended meaning of body image, including self-concept and the role function of relationship. This paper is expected to help nurses better understand the concept of body image and further apply this concept in clinical practice in order to improve the provision of humanistic patient-centered care.

Hydrogen breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in autism.

The aim of this study is to assess the prevalence of small intestinal bacterial overgrowth (SIBO) by hydrogen breath test in patients with autism spectrum disorders (ASD) with respect to a consistent control group. From 2011 to 2013, 310 children with ASD and 1240 sex- and age-matched typical children were enrolled in this study to undergo glucose breath test. The study participants were considered to exhibit SIBO when an increase in H2 of ≥20 ppm or CH4 of ≥10 ppm with respect to the fasting value was observed up to 60 min after the ingestion of glucose. Ninety-six children with autism suffered from SIBO, giving a prevalence rate of SIBO was 31.0% (95% CI 25.8-36.1%). In contrast, 9.3% of the typical children acknowledged SIBO. The difference between groups was statistically significant (P < 0.0001). The median Autism Treatment Evaluation Checklist (ATEC) score in the children with autism and with SIBO was significantly high when compared with the children without autism and without SIBO [98 (IQR, 45-120) vs. 63 (32-94), P < 0.001]. For the autism group, the 6-GI Severity Index (6-GSI) score was found to be strongly and significantly correlated with the total ATEC score (r = 0.639, P < 0.0001). SIBO was significantly associated with worse symptoms of autism, demonstrating that children with SIBO may significantly contribute to symptoms of autism.

Discrepancy between physicians' perceptions and practices during pelvic examinations in Taiwan.

OBJECTIVE: This study explored (1) physicians' perceptions of pelvic examination (PE) procedures and (2) the discrepancy between physicians' perceptions and their practices as observed by their attending nurses. METHOD: Data were collected from 20 physician-completed questionnaires on the perceived importance of 23 PE procedures. Each physician's practice of the same 23 PE procedures was assessed by 4-6 attending nurses (100 nurse observations). Physicians and nurses were sampled by convenience from the obstetrics/gynecology outpatient departments of 3 teaching hospitals in central Taiwan. Discrepancies between physicians' perceptions and their practices as assessed by attending nurses were examined by the Mann-Whitney U test. RESULTS: Physicians' mean scores ranged from 3.15 to 4.00, indicating that PE procedures were generally perceived as important. The procedures were rank ordered according to the mean scores from highest to lowest. Physicians' 5 top-ranking procedures were wearing gloves during the PE, asking agreement for the examination, paying attention to privacy during the PE, protecting the woman's personal information, and protecting the woman's medical records. Physicians' 5 lowest ranking procedures were telling the woman before inserting the speculum that she will feel some pressure, explaining the procedure before the PE, proactively providing information, asking the woman how she feels during the PE, asking a woman's permission to examine prior to commencing the PE, and describing observations to the woman during the PE (the last two procedures were tied for 5th rank). For 15 of the 23 PE procedures, physicians' perceptions did not differ significantly from their practices as assessed by attending nurses. The remaining 8 procedures were statistically significant between physicians' perception and their practices, and were rated higher by physicians (perception) than by attending nurses (practice). CONCLUSION: The 5 top-ranking PE procedures in terms of perceived importance were related to procedural behaviors, whereas the 5 lowest ranking procedures were verbal statements with explicit affective content. During nurse-observed PEs, Taiwanese physicians consistently practiced the procedural aspects of PEs they perceived as important (e.g., communication and consultation, protection and skilled technique, and confidentiality). However, physicians' practices were less consistent in affective aspects (e.g., explanation and consent, information and instruction, and sensitivity). PRACTICE IMPLICATIONS: Our results suggest that physicians should concentrate not only on procedural behaviors, but also on affective behaviors. These findings could be incorporated in medical education, particularly for medical students training to become obstetric and gynecological physicians.

Gynecologists' perception of the patient-physician relationship in pelvic examinations in Taiwan.

OBJECTIVE: To explore the gynecologists' physical contact and their interaction with patients, as well as the patient-physicians relationship during the pelvic examination (PE). STUDY DESIGN: This qualitative study uses face-to-face, in-depth interviews with 20 gynecologists from three hospitals in central Taiwan. RESULTS: The results revealed two main categories: adopting non-gendered and desexualised strategies and acknowledging a patient's situation. The majority of gynecologists adopted strategies to reduce their embarrassment during a PE, such as the use of a PE curtain, having a nurse in attendance, the tendency to depend on an ultrasound scan and the use of minimal verbal communication. CONCLUSION: Within the social context in Taiwan, male gynecologists tend to adopt a non-gendered and desexualised attitude to lessen the embarrassment and to protect them from accusations of sexual misconduct by patients during the PE. Acknowledging a patient's situation can benefit the gynecologists and allowed them to conduct the PE more easily. The results could possibly provide the medical student with an awareness and reflection of how social interaction plays a role for the gynecologists and their patients during a PE.

Decision-making tree for women considering hysterectomy.

AIMS: This paper reports on a study carried out to establish a decision tree model to describe how women in Taiwan make the decision whether or not to have a hysterectomy. In addition, we examined the predictability of the decision-tree model. BACKGROUND: Hysterectomy is the second most common surgical procedure performed worldwide. Medical professionals believe that the operation can relieve pain and prevent cervical cancer, thus improving a woman's quality of life. While most physicians advise hysterectomy even for benign uterine conditions, feminists decry the belief that the uterus has no purpose, believing that it is an important symbol of womanhood. METHODS: The study was conducted in two phases. Phase I, the model development phase, was carried out to generalize data from a qualitative study of 14 women and to establish a tree model outlining their decision to proceed with hysterectomy. The second phase was the model prediction phase that applied inductive and deductive methods to data analysis and development of the decision-tree model. The model tree was then tested with 18 women who were deciding whether or not to undergo hysterectomy. Using the decision-making tree, we studied the women's thought processes and analysed their primary concerns. The study was carried out in 1999-2001. RESULTS: The study determined 13 criteria that Taiwanese women use when deciding about having a hysterectomy. Developed in accordance with Gladwin's methodology, the model tree successfully predicted 90% of decisions whether or not to have a hysterectomy. CONCLUSIONS: Nurses working in gynaecological services should understand how women decide to undergo hysterectomy so that the proper counselling and follow-up can be provided. With further testing, our decision tree may help in this process.