Chronic pain is among the most prevalent burdensome disorders worldwide. The N-methyl-d-aspartate (NMDA) receptor system plays a critical role in central sensitization, a primary feature of chronic pain. Despite the proven efficacy of exogenous ligands to this receptor system in preclinical studies, evidence for the clinical efficacy of NMDA antagonists for the treatment of chronic pain is weak. Researchers are studying alternate approaches, rather than direct inhibition of the NMDA receptors in pain processing neurons. This indirect approach utilizes the modulation of molecular switches that regulates the synthesis, maturation, and transport of receptors from cellular organelles to the synaptic membrane. Kinesins are nanomotors that anterogradely transport the cargo using microtubule tracks across the neurons. Various members of the kinesin family, including KIF17, KIF11, KIF5b, and KIF21a, regulate the intracellular transport of NMDA receptors. Pharmacological targeting of these ATP-driven nanomotors could be a useful tool for manipulating the NMDAR functioning. It could provide the potential for the development of a novel strategy for the management of chronic pain.

Pain is one of the clinical manifestations that can vary from mild to severe symptoms in COVID-19 patients. Pain symptoms can be initiated by direct viral damage to the tissue or by indirect tissue injury followed by nociceptor sensitization. The most common types of pain that are reported to occur in COVID-19 patients are headache, myalgia, and chest pain. With more and more cases coming in the hospitals, many new and unique symptoms of pain are being reported. Testicular and abdominal pain are rare cases of pain that are also being reported and are associated with COVID-19. The SARS-CoV-2 virus has a high affinity for angiotensin-converting enzyme-2 receptor (ACE-2) which acts as an entry point for the virus. ACE-2/ Ang II/AT 1 receptor also participates directly in the transmission of pain signals from the dorsal horn of the spinal cord. It induces a series of complicated responses in the human body. Among which the cytokinetic storm and hypercoagulation are the most prominent pathways that mediate the sensitization of sensory neurons facilitating pain. The elevated immune response is also responsible for the activation of inflammatory lipid mediators such as COX-1 and COX-2 enzymes for the synthesis of prostaglandins (PGs). PG molecules especially PGE2 and PGD2 are involved in the pain transmission and are found to be elevated in COVID-19 patients. Though arachidonic acid pathway is one of the lesser discussed topics in COVID-19 pathophysiology, still it can be useful for explaining the unique and rarer symptoms of pain seen in COVID-19 patients. Understanding different pain pathways is very crucial for the management of pain and can help healthcare systems to end the current pandemic situation. We herein review the role of various molecules involved in the pain pathology of COVID-19.

No abstract

Homoeotic appendages provide a system for the analysis of neural path-finding in which the appendage is mismatched with its segmented ganglion. Central projections of sensory neurons from homoeotic antennapedia regenerates induced by antennal amputation in the stick insect, Carausius morosus, are described. The majority of afferent axons project to the olfactory lobe as in the normal antennal nerve, but they do not give rise to compact glomeruli. Nor does the form of the projection resemble that of leg sensory nerves in thoracic ganglia. The projection of antennapedia regenerate neurons in Carausius resembles the antennapedia mutant of Drosophila except that some primary afferents bypass the olfactory lobe and take several courses through the brain, sometimes reaching distant contralateral areas. It appears that these wandering fibers, having bypassed the olfactory lobe, tend to follow established tracts and to arborize or to deviate at circumscribed synaptic areas. The behavioral evidence for sensory input from antennapedia regenerates is equivocal.

Neurodegenerative disorders are threatening mankind with significant health and economic burden. Neurodegeneration involves the deterioration of neurons in the central nervous system (CNS), resulting in decreased neuronal survival. Therefore, it is of utmost requirement to develop a promising pharmacological strategy to minimize or prevent the progression of the underlying disease pathogenesis. In neurodegenerative disease conditions, neurons and glial cells present in the specific brain regions are damaged and depraved, resulting in specified disease symptoms in the patients. Neuroinflammation plays a major role in the degeneration of neuronal cells by regulating the expression of interleukin-1 beta (IL-1β), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokines Cxcl3 (C-C motif) ligand 2 (CCL2), CXCL5, granulocyte-macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), impaired tuning of immune cells and nuclear factor kappa-B (NF-κB). Considering this, it is very important to understand the in-depth role of neuroinflammation in the initiation and progression of various neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Huntington's Disease (HD), as well as Multiple Sclerosis (MS). Recent shreds of evidence have suggested that using exogenous ligands to approach various biological molecules or cellular functioning that modulates the neuroinflammation, such as microglia response, P2X7 receptors, TLR receptors, oxidative stress, PPARγ, NF-κB signaling pathway, NLRP3 inflammasome, caspase-1 signaling pathway, and mitochondrial dysfunction, helps to combat neurodegeneration in a variety of diseases. Thus, targeting the neuroinflammatory drive could provide a beacon for the management of neurodegenerative diseases. Here, we have attempted to provide comprehensive literature suggesting the role of neuroinflammation in neurodegeneration and its implication in the development of near-future neurotherapeutics.