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Author Response: Reationship Between Headache Characteristics and a Remote History of TBI in Veterans: A 10-Year Retrospective Chart Review.

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Reader Response: Relationship Between Headache Characteristics and a Remote History of TBI in Veterans: A 10-Year Retrospective Chart Review.

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Long-term opioid therapy among patients with systemic lupus erythematosus in the community. A Lupus Midwest Network study.

There is little information about the epidemiology and factors associated with opioid therapy in systemic lupus erythematosus (SLE). We aimed to assess the prevalence of opioid therapy and explore factors associated with long-term opioid therapy (LTOT) in patients with SLE.

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A Review of Long-acting Parenteral Analgesics for Mice and Rats.

Appropriate analgesia is a crucial part of rodent postoperative and postprocedural pain. Providing appropriate analgesia is an ethical obligation, a regulatory requirement, and an essential element of obtaining quality scientific results and conducting reproducible data. Meeting these requirements is facilitated by practical, efficient and safe delivery methods for providing analgesia. Over the last decade, long-acting analgesics have gained widespread use in research animal medicine to avoid or treat postoperative or postprocedural pain while minimizing handling-related time and stress. Long-acting formulations of analgesics suitable for rodents are available for opioids, NSAIDs, and local anesthetics. The goal of this review is to summarize the currently available long-acting formulations of analgesics for rodents and to provide recommendations to veterinarians and researchers regarding their use.

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Endometriosis: A multimodal imaging review.

Endometriosis is a chronic inflammatory disorder characterized endometrial-like tissue present outside of the uterus, affecting approximately 10% of reproductive age women. It is associated with abdomino-pelvic pain, infertility and other non – gynecologic symptoms, making it a challenging diagnosis. Several guidelines have been developed by different international societies to diagnose and classify endometriosis, yet areas of controversy and uncertainty remains. Transvaginal ultrasound (TV-US) is the first-line imaging modality used to identify endometriosis due to its accessibility and cost-efficacy. Enhanced sonographic techniques are emerging as a dedicated technique to evaluate deep infiltrating endometriosis (DIE), depending on the expertise of the sonographer as well as the location of the lesions. MRI is an ideal complementary modality to ultrasonography for pre-operative planning as it allows for a larger field-of-view when required and it has high levels of reproducibility and tolerability. Typically, endometriotic lesions appear hypoechoic on ultrasonography. On MRI, classical features include DIE T2 hypointensity, endometrioma T2 hypointensity and T1 hyperintensity, while superficial peritoneal endometriosis (SPE) is described as a small focus of T1 hyperintensity. Imaging has become a critical tool in the diagnosis, surveillance and surgical planning of endometriosis. This literature review is based mostly on studies from the last two decades and aims to provide a detailed overview of the imaging features of endometriosis as well as the advances and usefulness of different imaging modalities for this condition.

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Clinical hypnosis can reduce lower urinary tract symptoms in individuals with chronic pain.

Lower urinary tract symptoms (LUTS) can occur in chronic pain populations at high rates and drastically affect quality of life. Hypnosis is a nonpharmacological treatment used in chronic pain known to have beneficial implications to health outside of pain reduction. This study evaluated the potential for hypnosis to reduce LUTS in a sample of individuals with chronic pain, if baseline LUTS severity affected outcomes, and specific LUTS that may respond to hypnosis.

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Peripheral Ion Channel Genes Screening in Painful Small Fiber Neuropathy.

Neuropathic pain is a characteristic feature of small fiber neuropathy (SFN), which in 18% of the cases is caused by genetic variants in voltage-gated sodium ion channels. In this study, we assessed the role of fifteen other ion channels in neuropathic pain. Patients with SFN (n = 414) were analyzed for , , , , , , , , , , , , , and variants by single-molecule molecular inversion probes-next-generation sequencing. These patients did not have genetic variants in , and . In twenty patients (20/414, 4.8%), a potentially pathogenic heterozygous variant was identified in an ion-channel gene (ICG). Variants were present in seven genes, for two patients (0.5%) in , one (0.2%) in , two (0.5%) in , seven (1.7%) in , three (0.7%) in , three (0.7%) in and two (0.5%) in . Variants in the TRP genes were the most frequent (n = 15, 3.6%), partly in patients with high mean maximal pain scores VAS = 9.65 ± 0.7 (n = 4). Patients with ICG variants reported more severe pain compared to patients without such variants (VAS = 9.36 ± 0.72 vs. VAS = 7.47 ± 2.37). This cohort study identified ICG variants in neuropathic pain in SFN, complementing previous findings of ICG variants in diabetic neuropathy. These data show that ICG variants are central in neuropathic pain of different etiologies and provides promising gene candidates for future research.

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Identifying Risk Factors, Patient-Reported Experience and Outcome Measures, and Data Capture Tools for an Individualized Pain Prediction Tool in Pediatrics: Focus Group Study.

The perioperative period is a data-rich environment with potential for innovation through digital health tools and predictive analytics to optimize patients' health with targeted prehabilitation. Although some risk factors for postoperative pain following pediatric surgery are already known, the systematic use of preoperative information to guide personalized interventions is not yet widespread in clinical practice.

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Modulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine.

Preclinical data point to the contribution of transient receptor potential ankyrin 1 (TRPA1) channels to the complex mechanisms underlying migraine pain. TRPA1 channels are expressed in primary sensory neurons, as well as in glial cells, and they can be activated/sensitized by inflammatory mediators. The aim of this study was to investigate the relationship between TRPA1 channels and glial activation in the modulation of trigeminal hyperalgesia in preclinical models of migraine based on acute and chronic nitroglycerin challenges. Rats were treated with ADM_12 (TRPA1 antagonist) and then underwent an orofacial formalin test to assess trigeminal hyperalgesia. mRNA levels of pro- and anti-inflammatory cytokines, calcitonin gene-related peptide (CGRP) and glia cell activation were evaluated in the Medulla oblongata and in the trigeminal ganglia. In the nitroglycerin-treated rats, ADM_12 showed an antihyperalgesic effect in both acute and chronic models, and it counteracted the changes in CGRP and cytokine gene expression. In the acute nitroglycerin model, ADM_12 reduced nitroglycerin-induced increase in microglial and astroglial activation in trigeminal nucleus caudalis area. In the chronic model, we detected a nitroglycerin-induced activation of satellite glial cells in the trigeminal ganglia that was inhibited by ADM_12. These findings show that TRPA1 antagonism reverts experimentally induced hyperalgesia in acute and chronic models of migraine and prevents multiple changes in inflammatory pathways by modulating glial activation.

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The contribution of endocytosis to sensitization of nociceptors and synaptic transmission in nociceptive circuits.

Chronic pain involves sensitization of nociceptors and synaptic transmission of painful signals in nociceptive circuits in the dorsal horn of the spinal cord. We investigated the contribution of clathrin-dependent endocytosis to sensitization of nociceptors by G protein-coupled receptors (GPCRs) and to synaptic transmission in spinal nociceptive circuits. We determined whether therapeutic targeting of endocytosis could ameliorate pain. mRNA encoding dynamin (Dnm) 1-3 and adaptor-associated protein kinase 1 (AAK1), which mediate clathrin-dependent endocytosis, were localized to primary sensory neurons of dorsal root ganglia of mouse and human and to spinal neurons in the dorsal horn of the mouse spinal cord by RNAScope®. When injected intrathecally to mice, Dnm and AAK1 siRNA or shRNA knocked-down Dnm and AAK1 mRNA in dorsal root ganglia neurons, reversed mechanical and thermal allodynia and hyperalgesia, and normalized non-evoked behavior in preclinical models of inflammatory and neuropathic pain. Intrathecally administered inhibiters of clathrin, Dnm and AAK1 also reversed allodynia and hyperalgesia. Disruption of clathrin, Dnm and AAK1 did not affect normal motor functions of behaviors. Patch clamp recordings of dorsal horn neurons revealed that Dnm1 and AAK1 disruption inhibited synaptic transmission between primary sensory neurons and neurons in lamina I/II of the spinal cord dorsal horn by suppressing release of synaptic vesicles from presynaptic primary afferent neurons. Patch clamp recordings from dorsal root ganglion nociceptors indicated that Dnm siRNA prevented sustained GPCR-mediated sensitization of nociceptors. By disrupting synaptic transmission in the spinal cord and blunting sensitization of nociceptors, endocytosis inhibitors offer a therapeutic approach for pain treatment.

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