Blocking Neuropilin-1 in Drosophila melanogaster as a Possible Treatment for Pain and SARS-CoV-2

This study aims to validate a method of neuropilin-1 blocking in Drosophila melanogaster to aid the development of chronic pain treatment as well as increase scientific understanding of SARS-CoV-2 cell entry. If Drosophila melanogaster are exposed to monoclonal antibodies (mAbs) used for targeted chemotherapy against neuropilin-1, then this targeted protein blocking method may allow for the development of new pain treatment and possible SARS-CoV-2 treatment. mAbs were microinjected into mutant flies to block NRP-1 activity. Then, a thermal nociception and von frey assay were done to test drosophila nociception. Finally, an IHC assay was performed to quantify protein activity. Overall, the hypothesis was supported as both nociception assays showed significant data proving mutant flies had delayed or no reactions to stimuli. The Von Frey assay did show some varying results, but the data is still significant. However, the IHC did show that there was still some NRP-1 activity in the mutant flies. NRP-1 was able to be partially blocked by mAbs. The collected data may apply to the expansion of research in pain treatment as well as COVID-19 research. Chronic pain is a prevalent area of research that is still not completely solved today. The fight against the SARS-CoV-2 is an ongoing fight and further research is mandatory in finding treatments for this deadly virus.

A group-based chronic pain intervention using the Unlearn Your Pain method: A retrospective one-arm cohort study

LAY SUMMARY Chronic pain is a frequent occurrence in military and Veteran populations. This study examined whether a group-based chronic pain treatment using the Unlearn Your Pain method was effective in reducing chronic pain in 21 military and Veteran participants. Participants completed measures of pain before and after engaging in the treatment, and results showed participants experienced large reductions in total pain and pain-related catastrophizing and moderate reductions in pain-related disability and pain-related fear of movement after completing the treatment. A smaller group of the participants completed the measures again eight weeks after completing treatment, and the size of their improvements was even greater. This study offers preliminary support for the Unlearn Your Pain method offered in a group format to military and Veteran populations. Further study is warranted.

A patient-informed qualitative evaluation of an online chronic pain treatment for military, police, and Veterans

LAY SUMMARY In this study, members and Veterans of the Canadian Armed Forces were asked about their experiences with an online chronic pain treatment that had been specifically tailored to this population, as well as to members of the Royal Canadian Mounted Police. The purpose was to learn what participants in the treatment program liked and disliked about the program itself and the changes they would suggest to improve the program. The authors learned that despite the effort to tailor the treatment to this population, the voices of actual members of the population needed to be heard to truly tailor the program to their needs. The study provides insight into ways to refine the program to better match the unique characteristics of this population, their special connection to each other, and their individual differences. A revised version of the chronic pain program is being developed based on this feedback.

Melatonin Moderates the Triangle of Chronic Pain, Sleep Architecture and Immunometabolic Traffic

Preclinical as well as human studies indicate that melatonin is essential for a physiological sleep state, promotes analgesia and is involved in immunometabolic signaling by regulating neuroinflammatory pathways. Experimental and clinical neuromodulation studies for chronic pain treatment suggest that neurostimulation therapies such as spinal cord stimulation, vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. Herein, we provide an overview of current literature relevant for the shared pathways of sleep, pain and immunometabolism and elaborate the impact of melatonin on the crossroad of sleep, chronic pain and immunometabolism. Furthermore, we discuss the potential of melatonin as an adjunct to neurostimulation therapies. In this narrative review, we addressed these questions using the following search terms: melatonin, sleep, immunometabolism, obesity, chronic pain, neuromodulation, neurostimulation, neuroinflammation, molecular inflammatory phenotyping. So far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. Thus, the adjunct potential of melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation therapies.

Intranasal Administration for Pain: Oxytocin and Other Polypeptides

Pain, particularly chronic pain, remains one of the most debilitating and difficult-to-treat conditions in medicine. Chronic pain is difficult to treat, in part because it is associated with plastic changes in the peripheral and central nervous systems. Polypeptides are linear organic polymers that are highly selective molecules for neurotransmitter and other nervous system receptors sites, including those associated with pain and analgesia, and so have tremendous potential in pain therapeutics. However, delivery of polypeptides to the nervous system is largely limited due to rapid degradation within the peripheral circulation as well as the blood–brain barrier. One strategy that has been shown to be successful in nervous system deposition of polypeptides is intranasal (IN) delivery. In this narrative review, we discuss the delivery of polypeptides to the peripheral and central nervous systems following IN administration. We briefly discuss the mechanism of delivery via the nasal–cerebral pathway. We review recent studies that demonstrate that polypeptides such as oxytocin, delivered IN, not only reach key pain-modulating regions in the nervous system but, in doing so, evoke significant analgesic effects. IN administration of polypeptides has tremendous potential to provide a non-invasive, rapid and effective method of delivery to the nervous system for chronic pain treatment and management.