Endothelin-1 as a neuropeptide: neurotransmitter or neurovascular effects?

Endothelin-1 (ET-1) is an endothelium-derived peptide that also possesses potent mitogenic activity. There is also a suggestion the ET-1 is a neuropeptide, based mainly on its histological identification in both the central and peripheral nervous system in a number of species, including man. A neuropeptide role for ET-1 is supported by studies showing a variety of effects caused following its administration into different regions of the brain and by application to peripheral nerves. In addition there are studies proposing that ET-1 is implicated in a number of neural circuits where its transmitter affects range from a role in pain and temperature control to its action on the hypothalamo-neurosecretory system. While the effect of ET-1 on nerve tissue is beyond doubt, its action on nerve blood flow is often ignored. Here, we review data generated in a number of species and using a variety of experimental models. Studies range from those showing the distribution of ET-1 and its receptors in nerve tissue to those describing numerous neurally-mediated effects of ET-1

Minimizing the source of nociception and its concurrent effect on sensory hypersensitivity: An exploratory study in chronic whiplash patients

Abstract. Background. The cervical zygapophyseal joints may be a primary source of pain in up to 60% of individuals with chronic whiplash associated disorders (WAD) and may be a contributing factor for peripheral and centrally mediated pain (sensory hypersensitivity). Sensory hypersensitivity has been associated with a poor prognosis. The purpose of the study was to determine if there is a change in measures indicative of sensory hypersensitivity in patients with chronic WAD grade II following a medial branch block (MBB) procedure in the cervical spine. Methods. Measures of sensory hypersensitivity were taken via quantitative sensory testing (QST) consisting of pressure pain thresholds (PPT's) and cold pain thresholds (CPT's). In patients with chronic WAD (n = 18), the measures were taken at three sites bilaterally, pre- and post- MBB. Reduced pain thresholds at remote sites have been considered an indicator of central hypersensitivity. A healthy age and gender matched comparison group (n = 18) was measured at baseline. An independent t-test was applied to determine if there were any significant differences between the WAD and normative comparison groups at baseline with respect to cold pain and pressure pain thresholds. A dependent t-test was used to determine whether there were any significant differences between the pre and post intervention cold pain and pressure pain thresholds in the patients with chronic WAD. Results. At baseline, PPT's were decreased at all three sites in the WAD group (p < 0.001). Cold pain thresholds were increased in the cervical spine in the WAD group (p < 0.001). Post-MBB, the WAD group showed significant increases in PPT's at all sites (p < 0.05), and significant decreases in CPT's at the cervical spine (p < 0.001). Conclusions. The patients with chronic WAD showed evidence of widespread sensory hypersensitivity to mechanical and thermal stimuli. The WAD group revealed decreased sensory hypersensitivity following a decrease in their primary source of pain stemming from the cervical zygapophyseal joints

Depressive symptoms associated with COVID-19 preventive practice measures, daily activities in home quarantine and suicidal behaviors: findings from a large-scale online survey in Bangladesh

Background: The world is facing a public health emergency situation caused by the COVID-19 pandemic. Psychological wellbeing among individuals worldwide has been negatively affected by the pandemic especially in low- and middle-income countries such as Bangladesh. The present study aimed to assess the estimate of depressive symptoms and investigated its associations with COVID-19 preventive practice measures, daily activities in home quarantine, and suicidal behaviors in a large-scale Bangladeshi online survey. Methods: An online-based cross-sectional survey was widely distributed to Bangladeshi citizens. A total of 13,654 participants (61.0% male; mean age = 24.0 years [SD = 6.0]; age range 18–65 years) completed the survey between May and June (2020). The survey included socio-demographics and COVID-19-related questions, along with lifestyle, suicidal, and psychometric measures. Hierarchical regression was performed to determine significant associations between depression and examined variables. Results: The estimate of depressive symptoms during the COVID-19 pandemic was 43.5%. Based on hierarchical regression analysis, depression was significantly associated with not engaging in COVID-19 preventive measures, daily activities in home quarantine (e.g., playing videogames), and suicidal behaviors. Conclusions: Depressive symptoms appeared to be high during the COVID-19 pandemic in Bangladesh. To fight against the pandemic, mental health issues as well as physical health issues need to be taken into consideration

<i>Cis</i> P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI

Operational challenges in conducting a community-based technology-enabled mental health services delivery model for rural India: Experiences from the SMART Mental Health Project [version 1; referees: 3 approved]

Background: There are large gaps in the delivery of mental health care in low- and middle-income countries such as India, and the problems are even more acute in rural settings due to lack of resources, remoteness, and lack of infrastructure, amongst other factors. The Systematic Medical Appraisal Referral and Treatment (SMART) Mental Health Project was conceived as a mental health services delivery model using technology-based solutions for rural India. This paper reports on the operational strategies used to facilitate the implementation of the intervention. Method: Key components of the SMART Mental Health Project included delivering an anti-stigma campaign, training of primary health workers in screening, diagnosing and managing stress, depression and increased suicide risk and task sharing of responsibilities in delivering care; and using mobile technology based electronic decision support systems to support delivery of algorithm based care for such disorders. The intervention was conducted in 42 villages across two sites in the state of Andhra Pradesh in south India. A pre-post mixed methods evaluation was done, and in this paper operational challenges are reported. Results: Both quantitative and qualitative results from the evaluation from one site covering about 5000 adults showed that the intervention was feasible and acceptable, and initial results indicated that it was beneficial in increasing access to mental health care and reducing depression and anxiety symptoms. A number of strategies were initiated in response to operational challenges to ensure smoother conduct of the project and facilitated the project to be delivered as envisaged. Conclusions: The operational strategies initiated for this project were successful in ensuring the delivery of the intervention. Those, coupled with other more systematic processes have informed the researchers to understand key processes that need to be in place to develop a more robust study, that could eventually be scaled up

Evaluation of an anti-stigma campaign related to common mental disorders in rural India:a mixed methods approach

Background Stigma related to mental health is a major barrier to help-seeking resulting in a large treatment gap in low- and middle-income countries (LMIC). This study assessed changes in knowledge, attitude and behaviour, and stigma related to help-seeking among participants exposed to an anti-stigma campaign. Method The campaign, using multi-media interventions, was part of the SMART Mental Health Project, conducted for 3 months, across 42 villages in rural Andhra Pradesh, in South India. Mixed-methods evaluation was conducted in two villages using a pre-post design. Results A total of 1576 and 2100 participants were interviewed, at pre- and post-intervention phases of the campaign. Knowledge was not increased. Attitudes and behaviours improved significantly (p < 0.01). Stigma related to help-seeking reduced significantly (p < 0.05). Social contact and drama were the most beneficial interventions identified during qualitative interviews. Conclusion The results showed that the campaign was beneficial and led to improvement of attitude and behaviours related to mental health and reduction in stigma related to help-seeking. Social contact was the most effective intervention. The study had implications for future research in LMIC