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Itch is a cutaneous sensation that is critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report a subpopulation of itch-specific neurons in the ventrolateral orbital cortex (VLO) that is distinct from the pain-related neurons. Using a Tet-Off cellular labeling system, we showed that local inhibition or activation of these itch-specific neurons in the VLO significantly suppressed or enhanced itch-induced scratching, respectively, whereas the intervention did not significantly affect pain. Conversely, suppression or activation of pain-specific neurons in the VLO significantly affected pain but not itch. Moreover, fiber photometry and immunofluorescence verified that these itch- and pain-specific neurons are distinct in their functional activity and histological location. In addition, the downstream targets of itch- and pain-specific neurons were different. Together, the present study uncovers an important subpopulation of neurons in the VLO that specifically modulates itch processing.
Learn More >This narrative review highlights the interventional musculoskeletal techniques that have evolved in recent years.
Learn More >The perception of noxious environmental stimuli by nociceptive sensory neurons is an essential mechanism for the prevention of tissue damage. Etv4 is a transcriptional factor expressed in most nociceptors in dorsal root ganglia (DRG) during the embryonic development. However, its physiological role remains unclear. Here, we show that Etv4 ablation results in defects in the development of the peripheral peptidergic projections in vivo and deficits in axonal elongation and growth cone morphology in cultured sensory neurons in response to NGF. From a mechanistic point of view, our findings reveal that NGF regulates Etv4-dependent gene expression of molecules involved in extracellular matrix (ECM) remodeling. Etv4-null mice were less sensitive to noxious heat stimuli and chemical pain and this behavioral phenotype correlates with a significant reduction in the expression of the pain-transducing ion channel TRPV1 in mutant mice. Together, our data demonstrate that Etv4 is required for the correct innervation and function of peptidergic sensory neurons, regulating a transcriptional program that involves molecules associated to axonal growth and pain transduction.
Learn More >The benefits of preventive treatment on the effectiveness of migraine management have rarely been examined. This post hoc analysis investigated the impact of eptinezumab on the optimization of acute medication effectiveness using the 4-item Migraine Treatment Optimization Questionnaire (mTOQ-4) to measure acute medication optimization over 4 weeks post-infusion.
Learn More >Temporal summation of second pain (TSSP) has been suggested as a psychophysical index for central sensitization, one of the critical mechanisms in the chronification of pain. However, there is no gold standard for protocols to measure TSSP. The purpose was to establish the stimulus intensity for measuring TSSP. Female patients with chronic myofascial temporomandibular disorders pain (n = 16) and healthy female volunteers with no pain (n = 15) participated. Pain thresholds (PT °C) were measured, and repetitive heat stimuli at three stimulus intensities (PT °C, PT + 1 °C, PT + 2 °C) were applied. TSSP parameters were quantified as TSSP magnitude (TSm) and TSSP frequency (TSf). In healthy female volunteers, pain ratings significantly decreased at PT °C (p < 0.050), besides TSm and TSf at PT + 2 °C were significantly higher than those at PT °C (p < 0.025). In chronic pain patients, pain ratings significantly increased at PT + 1 °C and PT + 2 °C (p < 0.050). At PT + 2 °C, TSm and TSf in chronic pain patients were significantly higher than those in healthy volunteers (p < 0.050). It could be helpful to measure TSSP with the stimulus intensity adjusted individually to the patient's pain thresholds + 2 °C for assessing central sensitization.
Learn More >Patients with chronic postsurgical pain (CPSP) frequently exhibit comorbid cognitive deficits. Recent observations have emphasized the critical effects of gut microbial metabolites, like short-chain fatty acids (SCFAs), in regulating cognitive function. However, the underlying mechanisms and effective interventions remain unclear. According to hierarchical clustering and 16S rRNA analysis, over two-thirds of the CPSP rats had cognitive impairment, and the CPSP rats with cognitive impairment had an aberrant composition of gut SCFA-producing bacteria. Then, using feces microbiota transplantation, researchers identified a causal relationship between cognitive-behavioral and microbic changes. Similarly, the number of genera that generated SCFAs was decreased in the feces from recipients of cognitive impairment microbiota. Moreover, treatment with the SCFAs alleviated the cognitive-behavioral deficits in the cognitively compromised pain rats. Finally, we observed that SCFA supplementation improved histone acetylation and abnormal synaptic transmission in the medial prefrontal cortex (mPFC), hippocampal CA1, and central amygdala (CeA) area via the ACSS2 (acetyl-CoA synthetase2)-HDAC2 (histone deacetylase 2) axis. These findings link pain-related cognition dysfunction, gut microbiota, and short-chain fatty acids, shedding fresh insight into the pathogenesis and therapy of pain-associated cognition dysfunction.
Learn More >Pain is an unpleasant sensory and emotional experience. Understanding the neural mechanisms of acute and chronic pain and the brain changes affecting pain factors is important for finding pain treatment methods. The emergence and progress of non-invasive neuroimaging technology can help us better understand pain at the neural level. Recent developments in identifying brain-based biomarkers of pain through advances in advanced imaging can provide some foundations for predicting and detecting pain. For example, a neurologic pain signature (involving brain regions that receive nociceptive afferents) and a stimulus intensity-independent pain signature (involving brain regions that do not show increased activity in proportion to noxious stimulus intensity) were developed based on multivariate modeling to identify processes related to the pain experience. However, an accurate and comprehensive review of common neuroimaging techniques for evaluating pain is lacking. This paper reviews the mechanism, clinical application, reliability, strengths, and limitations of common neuroimaging techniques for assessing pain to promote our further understanding of pain.
Learn More >While most individuals physically injured at work will make a complete medical recovery, a portion of workers will experience persistent pain following their injury. This study estimated persistent pain prevalence and its association with health and return-to-work outcomes 18 months following the incidence of a disabling work-related injury.
Learn More >Chronic overlapping pain conditions (COPCs) are a collection of chronic pain syndromes that often co-occur and are thought to share underlying nociplastic pathophysiology. Since they can manifest as seemingly unrelated syndromes they have historically been studied in isolation. Use of International Classification of Diseases (ICD) codes in medical records has been proposed as a means to identify and study trends in COPCs at the population level, however validated code sets are needed. Recently, a code set comprising ICD-10 codes as proxies for 11 COPCs was validated. The goal of this project was to validate a code set composed of ICD-9 codes for the identification of COPCs in administrative datasets. Data was extracted using the Electronic Medical Record Search Engine at the University of Michigan Health System from January 1st, 2011 to January 1st, 2015. The source population were patients with one of the candidate ICD-9 codes corresponding to various COPCs. Natural language searches were used as a reference standard. If code sets met a pre-specified threshold of agreement between ICD-9 codes and natural language searches (≥ 70%), they were retained and diagnostic accuracy statistics were calculated for each code set. Validated ICD-9 code sets were generated for 10 of the 11 COPCs evaluated. The majority had high levels of diagnostic accuracy, with all but one code set achieving ≥ 80% specificity, sensitivity, and predictive values. This code set may be used by pain researchers to identify COPCs using ICD-9 codes in administrative datasets.
Learn More >Headache is the most frequent symptom of cerebral venous thrombosis (CVT) but there is limited information about the frequency and phenotype of headache, weeks to months after cerebral venous thrombosis (post-cerebral venous thrombosis headache, post cerebral venous thrombosis headache).
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