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Pharmacological target-focused transcriptomic analysis of native vs cultured human and mouse dorsal root ganglia.

Dorsal root ganglion (DRG) neurons detect sensory inputs and are crucial for pain processing. They are often studied in vitro as dissociated cell cultures with the assumption that this reasonably represents in vivo conditions. However, to the best of our knowledge, no study has directly compared genome-wide transcriptomes of DRG tissue in vivo versus in vitro or between laboratories and culturing protocols. Comparing RNA sequencing-based transcriptomes of native to cultured (4 days in vitro) human or mouse DRG, we found that the overall expression levels of many ion channels and G-protein-coupled receptors specifically expressed in neurons are markedly lower although still expressed in culture. This suggests that most pharmacological targets expressed in vivo are present under the condition of dissociated cell culture, but with changes in expression levels. The reduced relative expression for neuronal genes in human DRG cultures is likely accounted for by increased expression of genes in fibroblast-like and other proliferating cells, consistent with their mitotic status in these cultures. We found that the expression of a subset of genes typically expressed in neurons increased in human and mouse DRG cultures relative to the intact ganglion, including genes associated with nerve injury or inflammation in preclinical models such as BDNF, MMP9, GAL, and ATF3. We also found a striking upregulation of a number of inflammation-associated genes in DRG cultures, although many were different between mouse and human. Our findings suggest an injury-like phenotype in DRG cultures that has important implications for the use of this model system for pain drug discovery.

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The Italian Fibromyalgia Registry: a new way of using routine real-world data concerning patient-reported disease status in healthcare research and clinical practice.

Fibromyalgia (FM), the most frequently encountered cause of widespread musculoskeletal pain, affects an estimated 2% of the general Italian population. However, it is not a homogeneous clinical entity, and a number of interacting factors can influence patient prognosis and the outcomes of standardised treatment programmes. Registries are a source of high-quality data for clinical research, but relating this information to individual patients is technically challenging. The aim of this article is to describe the structure and objectives of the first Italian Fibromyalgia Registry (IFR), a new web-based registry of patients with FM.

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The neurobiology of social stress resulting from Racism: Implications for pain disparities among racialized minorities.

Extant literature posits that humans experience two types of threat: physical threat and social threat. While describing pain as "physical" or "social" can be helpful for understanding pain origins (i.e., broken bone versus lost relationship), this dichotomy is largely artificial and not particularly helpful for understanding how the human brain experiences pain. One real world example of social exclusion and rejection that is threatening and likely to bring about significant stress is racism. Racism is a system of beliefs, practices, and policies that operates to disadvantage racialized minorities while providing advantage to those with historical power, particularly White people in the United States and most other Western nations. The objective of this Mini-Review is to present evidence in support of the argument that racism promotes physical pain in racialized minorities, which in turn promotes chronic pain disparities. First, we provide a theoretical framework describing how racism is a potent stressor that affects the health and well-being of racialized minorities. We will then address the neurobiological underpinnings linking racism to social threat, as well as that linking social threats and physical pain. Finally, we will discuss how the perception of social threat brought about by racism may undermine pain management efforts.

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The evaluation and brain representation of pleasant touch in chronic and subacute back pain.

If touch is perceived as pleasant, it can counteract the experience of pain. However, its pain-inhibitory function might be disturbed in chronic pain and this could contribute to pain-related interference. We investigated the perception of pleasant touch and its brain correlates in chronic back pain patients (CBP) compared to subacute back pain patients (SABP) and healthy controls (HC) using soft brush strokes. CBP showed less positive evaluations of touch. We found the highest activation in somatosensory and insular cortices in CBP, ventral striatum (VS) in SABP, and the orbitofrontal cortex in HC. Brain responses were significantly positively correlated with pleasantness ratings in HC and SABP, but not CBP. Further, the insula responses in CBP were positively correlated with pain-related interference and the VS activation in SABP correlated negatively with affective distress. Brain and behavioral changes in the processing of touch and its pleasantness may be a marker of pain chronicity and raise questions about the therapeutic value of pleasant touch in pain prevention and treatment.

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ICD-10 codes for the study of chronic overlapping pain conditions in administrative databases.

Chronic Overlapping Pain Conditions (COPCs) are a set of painful chronic conditions characterized by high levels of co-occurrence. It has been hypothesized that COPCs co-occur in many cases because of common neurobiological vulnerabilities. In practice, most research on COPCs has focused upon a single index condition with little effort to assess comorbid painful conditions. This likely means that important phenotypic differences within a sample are obscured. The International Classification of Diseases (ICD) coding system contains many diagnostic classifications that may be applied to individual COPCs, but there is currently no agreed upon set of codes for identifying and studying each of the COPCs. Here we seek to address this issue through three related projects: a) we first compile a set of ICD-10 codes from expert panels for ten common COPCs, b) we then use natural language searches of medical records to validate the presence of COPCs in association with the proposed expert codes, c) finally, we apply the resulting codes to a large administrative medical database to derive estimates of overlap between the ten conditions as a demonstration project. The codes presented can facilitate administrative database research on COPCs. Perspective: This article presents a set of ICD-10 codes that researchers can use to explore the presence and overlap of Chronic Overlapping Pain Conditions (COPCs) in administrative databases. This may serve as a tool for estimating samples for research,exploring comorbidities and treatments for individual COPCs, and identifying mechanisms associated with their overlap.

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Development of a topical menthol stimulus to evaluate cold hyperalgesia.

Cold hyperalgesia is an indicator of widespread pain sensitivity and is associated with poor clinical outcomes. Menthol activates TRPM8, a cold-sensing receptor channel. This research evaluated topical menthol as a potential stimulus to be used in the clinical evaluation of cold hyperalgesia.

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Headache related alterations of visual processing in migraine patients.

Migraine is characterized by an increased sensitivity to visual stimuli that worsens during attacks. Recent evidence has shown that feedforward volleys carrying incoming visual information induce high frequency (gamma) oscillations in the visual cortex, while feedback volleys arriving from higher order brain areas induce oscillatory activity at lower frequencies (theta/alpha/low-beta). We investigated visually induced high (feedforward) and low (feedback) frequency activations in healthy subjects and various migraine patients. Visual evoked potentials from 20 healthy controls and 70 migraine patients (30 inter-ictal and 20 ictal episodic migraineurs, 20 chronic migraineurs) were analysed in the frequency domain. We compared power in the theta-alpha-low beta and gamma range between groups, and searched for correlations between the low-to-high frequency activity ratio and number of monthly headache and migraine days. Compared to healthy controls, inter-ictal migraine patients had increased visually induced low frequency (feedback) activity. Conversely, ictal and chronic migraine patients showed an augmented gamma band (feedforward) power. The low-frequency-to-gamma (feedback/feedforward) activity ratio correlated negatively with monthly headache days and tended to do so with migraine days. Our findings show that visual processing is differentially altered depending on migraine cycle and type. Feedback control from higher order cortical areas predominates interictally in episodic migraine while migraine attacks and chronic migraine are associated with enhanced incoming afferent activity, confirming their similar electrophysiological profile. The presence of headache is associated with proportionally higher gamma (feedforward) activities. Perspective: This study provides an insight into the pathophysiology of migraine headache from the perspective of cortical sensory processing dynamics. Patients with migraine present alterations in feedback and feedforward visual signalling that differ with the presence of headache.

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Peripheral Neuropathy Evaluations of Patients With Prolonged Long COVID.

Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

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Stress-induced analgesia: an evaluation of effects on temporal summation of pain and the role of endogenous opioid mechanisms.

Acute stress reduces responses to static evoked pain stimuli (stress-induced analgesia [SIA]). Whether SIA inhibits temporal summation of pain, a dynamic evoked pain measure indexing central sensitization, has been little studied and mechanisms were not evaluated.

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Cervical Muscle Tenderness in Temporomandibular Disorders and Its Associations with Diagnosis, Disease-Related Outcomes, and Comorbid Pain Conditions.

To analyze cervical tenderness scores (CTS) in patients with various temporomandibular disorders (TMD) and in controls and to examine associations of CTS with demographic and clinical parameters.

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