An objective and automated method for evaluating abdominal hyperalgesia in a rat model for endometriosis.

Chronic pain and subfertility are the main symptoms of concern in women with endometriosis. In order to find new therapeutic options to suppress the pain, translational animal models are indispensable. We have developed a new automated, experimental setup, with full consideration for animal wellbeing, to determine whether operant behaviour can reveal abdominal hyperalgesia in rats with surgically-induced endometriosis, in order to assess whether abdominal hyperalgesia affect behavioural parameters. Endometriosis was induced by transplantation of uterine fragments in the abdominal cavity. Control groups consisted of sham-operated rats and non-operated rats. We have developed an operant chamber (Skinnerbox) which includes a barrier. The rat can climb the barrier in order to reach the food pellet, increasing in this way the pressure to the abdomen. We show that endometriosis rats collect significantly less sugar pellets when compared with the control rats after the introduction of the barrier. In the Skinnerbox experiment, we showed that in a positive operant setting, the introduction of a barrier results in a contrast of operant behaviour of endometriosis rats and control groups, perchance as a result of abdominal discomfort/hyperalgesia due to surgically-induced endometriosis. This is a promising start for the further development of a refined animal model to monitor abdominal discomfort/hyperalgesia in rats with surgically-induced endometriosis.

The Clinical Testing of the Serious Game Digest-Inn: A Tool to Increase Diet Adherence in Overweight Individuals.

Objective: Overweight and obesity are serious health issues often caused by a combination of high-energy consumption and limited physical activity. Diets that focus on limiting the energy intake are effective in the short term, but adherence to a diet is difficult and many individuals drop out prematurely. Materials and Methods: The serious game Digest-Inn is designed to increase diet adherence and to stimulate physical activity. The game was evaluated in three studies, assessing playability (in the general population; N = 76), usefulness (in dietetics practice; N = 7), and effectiveness (in reducing weight in overweight individuals; N = 47). Results: In the 3 studies, in total, 108 individuals played the game. The results show that the game supports dietetics practice and increases the effectiveness of the diet as prescribed by a dietitian. Overweight subjects showed an increased diet adherence (from 45% [in nonplayers] to 100% [in players]), increased weight loss (2.2 kg), and their physical activity was 3800 steps per day, during an average study period of 1 month. Conclusion: These results indicate that the game Digest-Inn is valued by dietitians to support the treatment of overweight clients. The game increases the adherence, and the game mechanics may also be of use for other conditions that suffer from low compliance and treatment adherence.

Experimental pain tolerance is decreased and independent of clinical pain intensity in patients with endometriosis.

OBJECTIVE: To investigate alterations in tactile, pain thresholds and pain tolerance thresholds in patients with endometriosis using a multimodality approach. DESIGN: Cross-sectional study. SETTING: Multidisciplinary referral center. PATIENT(S): Women with proven endometriosis (N = 35) and healthy controls (N = 38). INTERVENTION(S): Pain processing was tested using quantitative sensory testing (QST) to investigate sensation, pain, and pain tolerance thresholds for thermal, electrical, and pressure stimuli. MAIN OUTCOME MEASURE(S): Differences in QST measures in patients with endometriosis and in healthy controls on the endometriosis site and control sites, and the association between QST outcomes and patient characteristics. RESULT(S): We observed a significantly decreased pain tolerance in patients with endometriosis, independent of clinical pain intensity or revised American Society for Reproductive Medicine stage, compared with healthy controls. CONCLUSION(S): Increasing knowledge concerning mechanisms underlying the pain of women with endometriosis creates opportunities to develop new treatment options. More attention should be paid not only to treat endometriosis in a surgical or pharmacologic way, but also to desensitize by pain education or cognitive therapy.

Hair cortisol and the relationship with chronic pain and quality of life in endometriosis patients.

Endometriosis is a chronic estrogen-dependent disease in which pelvic pain is the dominant symptom. The negative effects of endometriosis on the life of women with this disease can be a cause of stress. Stress levels can be measured in different ways, mostly reflecting acute stress responses. Hair cortisol measurements are a reflection of long-term systematic cortisol levels. In this study a first attempt is made to measure cortisol levels in hair of endometriosis patients in comparison with healthy controls. Moreover, it is explored whether chronic pain symptoms as well as different aspects of Health Related Quality of Life (HRQoL) are associated with hair cortisol levels in women with endometriosis. Results show that the mean hair cortisol level is significantly higher in women with endometriosis compared to healthy controls (p = 0.018). There is a positive correlation between hair cortisol level and HRQoL in patients but not in controls (Rho 0.426). The level of hair cortisol does not correlate with the reported pain intensity in patients (Rho -0.082). These results are indicative of an altered HPA-axis function in endometriosis patients, possibly caused by higher chronic stress level in these patients. Moreover, a potential explanation for the positive correlation of cortisol with the HRQoL in these patients is that patients with a high HRQoL have an adequate stress response by increasing their cortisol levels as a response to physical and emotional stress induced by the endometriosis.

Risk-taking and pathological gambling behavior in Huntington's disease.

Huntington's disease (HD) is a genetic, neurodegenerative disorder, which specifically affects striatal neurons of the indirect pathway, resulting in a progressive decline in muscle coordination and loss of emotional and cognitive control. Interestingly, predisposition to pathological gambling and other addictions involves disturbances in the same cortico-striatal circuits that are affected in HD, and display similar disinhibition-related symptoms, including changed sensitivity to punishments and rewards, impulsivity, and inability to consider long-term advantages over short-term rewards. Both HD patients and pathological gamblers also show similar performance deficits on risky decision-making tasks, such as the Iowa Gambling Task (IGT). These similarities suggest that HD patients are a likely risk group for gambling problems. However, such problems have only incidentally been observed in HD patients. In this review, we aim to characterize the risk of pathological gambling in HD, as well as the underlying neurobiological mechanisms. Especially with the current rise of easily accessible Internet gambling opportunities, it is important to understand these risks and provide appropriate patient support accordingly. Based on neuropathological and behavioral findings, we propose that HD patients may not have an increased tendency to seek risks and start gambling, but that they do have an increased chance of developing an addiction once they engage in gambling activities. Therefore, current and future developments of Internet gambling possibilities and related addictions should be regarded with care, especially for vulnerable groups like HD patients.

Synthesis and SAR studies of novel 2-(4-oxo-2-aryl-quinazolin-3(4H)-yl)acetamide vasopressin V1b receptor antagonists.

Synthesis and structure-activity relationships (SAR) of a novel series of vasopressin V(1b) (V(3)) antagonists are described. 2-(4-Oxo-2-aryl-quinazolin-3(4H)-yl)acetamides have been identified with low nanomolar affinity for the V(1b) receptor and good selectivity with respect to related receptors V(1a), V(2) and oxytocin (OT). Optimised compound 12j demonstrates a good pharmacokinetic profile and activity in a mechanistic model of HPA dysfunction.