Accepted

Offset analgesia is defined by a dramatic drop in perceived pain intensity with a relatively small decrease in noxious input. Although functional magnetic resonance imaging studies implicate subcortical descending inhibitory circuits during offset analgesia, the role of cortical areas remains unclear. The current study identifies cortical correlates of offset analgesia using functional near infrared spectroscopy (fNIRS). Twenty-four healthy volunteers underwent fNIRS scanning during offset (OS) and control (Con) heat stimuli applied to the forearm. After controlling for non-neural hemodynamic responses in superficial tissues, widespread increases in cortical oxygenated hemoglobin concentration were observed, reflecting cortical activation during heat pain. OS – Con contrasts revealed deactivations in bilateral medial prefrontal cortex (mPFC) and bilateral somatosensory cortex (SSC) associated with offset analgesia. Right dorsolateral prefrontal cortex (dlPFC) showed activation only during OS. These data demonstrate opposing cortical activation patterns during offset analgesia and support a model in which right dlPFC underlies ongoing evaluation of pain intensity change. With predictions of decreasing pain intensity, right dlPFC activation likely inhibits ascending noxious input via subcortical pathways resulting in SSC and mPFC deactivation. This study identifies cortical circuitry underlying offset analgesia and introduces the use of fNIRS to study pain modulation in an outpatient clinical environment.

This is a summary of the published research from the 14 observational, longitudinal and big-data, epidemiological studies supported by the LIMBIC-CENC program from 2013-2021 examining the long-term effects of combat-related traumatic brain injury (TBI). Findings from these 43 primary and secondary analyses include: 1) unique fluid, advanced neuroimaging and electrophysiologic biomarkers associated with mild traumatic brain injury (mTBI), number of mTBIs and related dysfunction, 2) increases in a range of chronic difficulties, including neurosensory, sleep, pain, cognitive deficits, behavioral disorders, overall symptom burden, healthcare costs and service-connected disability, associated with mTBI, all-severity traumatic brain injury (TBI), blast exposure, and number of mTBIs, and 3) increases in the risk for suicide and neurodegeneration, including dementia and Parkinson's disease, associated with mTBI and all-severity TBI. Ongoing LIMBIC-CENC longitudinal and epidemiologic research will clarify, confirm and expand upon these findings.

Alcoholic neuropathy emerges following the persistent alcohol imbibing, and triggers nerve damage through de-escalating the receptors situated in the central nervous system (CNS), which consecutively evolves into debilitating neuropathic state and further precipitates hyperalgesia, allodynia, dysesthesia, ataxia, numbness, immobility, and decline in certain body functions. Existing pharmacotherapy, such as anticonvulsants (gabapentin and topiramate), and antidepressant drugs (duloxetine, and venlafaxine) render short-lasting benefits; however, their continual use is not favoured nowadays because of their detrimental outcomes and habit-forming behaviour. Consequently, the research is being shifted towards exploring novel propitious targets which entirely assist in the cessation of the disease. This review discloses the multitudinous pathways implicated in the pathogenesis of alcoholic neuropathy, with special emphasis on purinergic and orexinergic receptors. Moreover, the review focuses on targeting purinergic (P2X, P2X, P2X, P2X, and P2Y), and orexinergic (OX1 and OX2) receptors associated with the evolution of alcoholic neuropathy, and to incentivize further investigation to attain novel propitious strategy in alcoholic neuropathy treatment. The mechanisms implicated in the progression of alcoholic neuropathy comprises malnourishment (B vitamins scarcity), direct pernicious outcomes of alcohol, increased oxidative-nitrosative stress, protein kinase C epsilon (PKCε), and extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) functioning, abnormalities in the axonal transport and cytoskeleton system, activation of nuclear factor-kappa B (NF-κB) and caspase pathway, stimulation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis, and microglial cells of spinal column. The purinergic receptor antagonists, orexins/orexinergic receptor antagonists eliminate/modulate hyperalgesia, allodynia, inflammatory pain, liberation of inflammatory mediators, NF-κB signalling pathway, ROS formation, nerve cell deterioration, and craving for alcohol consumption, thereby ceasing the evolution of alcoholic neuropathy. The authors focus to highlight the importance of this alternative strategy as a novel target in alcoholic neuropathy, and to incentivize researchers to scrutinize the possible benefits of purinergic and orexins/orexinergic receptors in the therapy of alcoholic neuropathy.

Despite the rapid advance in anti-cancer treatment in recent years, the treatment to cancer-related pain remains largely unchanged. One systemic review has shown that approximately 32% of patient with cancer-related pain were undertreated. While in patients responding to strong opioids, long-term use of opioids will lead to many undesired side effects such as constipation, tolerance, and addiction. The goals of this review are to re visit the current algorism of cancer pain management and bring attention to the emerging interventional pain management techniques.