Pain

Chronic migraine (CM) is a disabling neurologic disorder that affects approximately 2% of the general population. Neuroimaging studies show functional involvement of trigeminal structures, such as the trigeminal spinal nucleus (Sp5) in migraine. However, structural changes in the Sp5 and the afferent trigeminal spinal tract (sp5) have never been found. The aim of this study was to test the hypothesis that white matter changes in the sp5 are a key feature of brain alterations in CM patients. We used diffusion Magnetic Resonance Imaging (dMRI) and polarized light imaging (PLI) of post mortem brainstem specimens from healthy controls (n = 5) and CM patients (n = 5) to study white matter alterations in the sp5...

Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety, and to test their link to substance use in adolescents.By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16+1...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Little is known about the factors that influence providers' perceptions of patient risk for aberrant opioid use. Patient gender may interact with prior opioid misuse to influence these perceptions. We asked 131 physicians to view videos and vignettes for 8 virtual patients with chronic pain. Gender (male/female) and previous prescription opioid misuse (present/absent) varied across patients; the vignettes were otherwise balanced on demographic and clinical characteristics. For each patient, providers assessed four risk domains: opioid-related adverse events, opioid misuse/abuse, opioid addiction, and opioid diversion...

Purpose of this study was to examine the discriminative properties of the three-item PEG questionnaire for grading impact of non-dental orofacial pain.286 consecutive patients with orofacial pain of non-dental origin filled out the PEG questionnaire and Graded Chronic Pain Scale (GCPS, version 2). Correlation between the PEG and GCPS scores, internal consistency of the PEG, and differences between groups were examined statistically (level of significance: p≤0.05).The mean(±SD) age of the 213 patients (158 female) who were included in the analysis was 43...

Opioids relieve acute pain, but there is little evidence to support the stability of the benefit over long-term treatment of chronic noncancer pain. Previous systematic reviews consider only group level published data which did not provide adequate detail. Our goal was to use patient-level data to explore the stability of pain, opioid dose, and either physical function or pain interference in patients treated for 12 months with abuse deterrent formulations of oxycodone and hydrocodone. All available studies in the Food and Drug Administration Document Archiving, Reporting, and Regulatory Tracking System were included...

No abstract text is available yet for this article.

The opioid receptors are important regulators of pain, reward, and addiction. Limited evidence suggests the mu and delta opioid receptors form a heterodimer (MDOR), which may act as a negative feedback brake on opioid-induced analgesia. However, evidence for the MDOR in vivo is indirect and limited, and there are few selective tools available. We recently published the first MDOR-selective antagonist, D24M, allowing us to test the role of the MDOR in mice. We thus co-treated CD-1 mice with D24M and opioids in tail flick, paw incision, and chemotherapy-induced peripheral neuropathy pain models...

Research on intersectionality and chronic pain disparities is very limited. Intersectionality explores the interconnections between multiple aspects of identity and provides a more accurate picture of disparities. This study applied a relatively novel statistical approach (i.e., Latent Class Analysis; LCA) to examine chronic pain disparities with an intersectional identity approach. Cross-sectional data were analyzed using pre-treatment data from the Learning About My Pain (LAMP) trial, a randomized comparative effectiveness study of group-based psychosocial interventions (PCORI Contract #941, Beverly Thorn, PI; clinicaltrials...

Peripheral nerve injuries result in pronounced alterations in dorsal root ganglia (DRG), which can lead to the development of neuropathic pain. Although the polymodal mechanosensitive transient receptor potential ankyrin 1 ion channel (TRPA1) is emerging as a relevant target for potential analgesic therapies, preclinical studies do not provide unequivocal mechanistic insight into its relevance for neuropathic pain pathogenesis. By utilizing a transgenic mouse model with a conditional depletion of the interleukin-6 signal transducer gp130 in Nav1...

and loss-of-function mutations in Nav1.7 cause chronic pain and pain insensitivity, respectively. The preferential expression of Nav1.7 in peripheral nervous system and its role in human pain signaling make Nav1.7 a promising target for next-generation pain therapeutics. However, pharmacological agents have not fully recapitulated these pain phenotypes, and, due to the lack of subtype-selective molecular modulators, the role of Nav1.7 in the perception of pain remains poorly understood. Scorpion venom is an excellent source of bioactive peptides that modulate various ion channels, including voltage-gated sodium (Nav) channels ...

Group I metabotropic glutamate receptors (mGluR1 and mGluR5, mGluR1/5) have been implicated in several CNS diseases including chronic pain. It is known that activation of mGluR1/5 results in production of inositol triphosphate (IP3) and diacylglycerol (DAG) that leads to activation of extracellular signal-regulated kinases (ERK1/2) and an increase in neuronal excitability, but how mGluR1/5 mediate this process remains unclear. We previously reported that Orai1 is responsible for store-operated calcium entry (SOCE) and plays a key role in central sensitization...

Dietary interventions are promising approaches to treat pain associated with metabolic changes because they impact both metabolic and neural components contributing to painful neuropathy. Here, we tested whether consumption of a ketogenic diet could affect sensation, pain, and epidermal innervation loss in type 1 diabetic mice. C57Bl/6 mice were rendered diabetic using streptozotocin and administered a ketogenic diet at either three weeks (prevention) or nine weeks (reversal) of uncontrolled diabetes. We quantified changes in metabolic biomarkers, sensory thresholds, and epidermal innervation to assess impact on neuropathy parameters...

Ketamine is often used in pain clinics for refractory chronic pain, but its long-term efficacy is poorly reported. The main objective was to assess the long-term effect of ketamine on pain and health variables in patients with refractory chronic pain.A prospective, multicenter, one-year follow-up observational study (NCT03319238) was conducted in thirty French pain clinics where ketamine is commonly prescribed. This study focused on patients with one ketamine delivery procedure (n=256). The primary endpoint was pain intensity (0-10 numerical pain rating scale) before and after ketamine every month for one year...

Recent research has highlighted the need for a deeper understanding of the heterogeneity in trajectories of children's distress following acute pain exposure, moving beyond group means of behavioural pain scores at a single timepoint. During preschool vaccinations, three distinct trajectories of post-vaccination pain regulation have been elucidated, with approximately 75% of children displaying trajectories characterized by down-regulation to no distress by two minutes post-needle and 25% concerningly failing to down-regulate by two-minutes...

Knowledge of etiological mechanisms underlying whiplash-associated disorders (WAD) is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in WAD would facilitate diagnosis, strengthen patients' subjective pain reports and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study we evaluated combined [11C]D-deprenyl positron emission tomography and computed tomography (PET-CT)) after acute whiplash injury and at 6 month follow-up...

Painful diabetic neuropathy (PDN) is an intractable complication affecting 25% of diabetic patients. PDN is characterized by neuropathic pain accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability, resulting in calcium overload, axonal degeneration, and loss of cutaneous innervation. The molecular pathways underlying these effects are unknown. Using high-throughput and deep-proteome profiling, we found that mitochondrial fission proteins were elevated in DRG neurons from mice with PDN induced by a high-fat diet (HFD)...

Pain and other somatosensory sensations, such as itch, can be effectively decreased by placebo effects and increased by nocebo effects. There are indications that placebo effects on pain generalize to other sensations and that nocebo effects generalize within itch modalities. However, it has not yet been investigated whether learned effects can generalize within pain stimulus modalities or from pain to itch. Our aims were to test whether placebo and nocebo effects can generalize within pain modalities, i.e...

Clinical evidence indicates dorsal root ganglion (DRG) stimulation effectively reduces pain without the need to evoke paresthesia. This paresthesia-free anesthesia by DRG stimulation can be promising to treat pain from the viscera, where paresthesia usually cannot be produced. Here, we explored the mechanisms and parameters for DRG stimulation using an ex vivo preparation with mouse distal colon and rectum (colorectum), pelvic nerve, L6 DRG, and dorsal root in continuity. We conducted single-fiber recordings from split dorsal root and assessed the effect of DRG stimulation on afferent neural transmission...