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To examine the annual healthcare expenditures associated with childhood headache in the United States, and to evaluate whether psychiatric comorbidities increase the impact of headache on expenditures.
Learn More >To address the need for long-term lasmiditan data, the GLADIATOR study evaluated the safety (primary) and efficacy (secondary) of lasmiditan for the intermittent, acute treatment of migraine attacks for up to 1 year.
Learn More >Neuropathic pain is one of most intense types of chronic pain. Numerous studies investigating neuropathic pain have described the critical involvement of microglia in the spinal cord. Previous studies have indicated that activation of large conductance Ca2+‑activated K+ (BK) channels contributes to microglial activation in the spinal dorsal horn (SDH) and the generation of neuropathic pain. However, the specific role of BK channels in spinal microglia in neuropathic pain has not been fully addressed in previous studies, as BK channel inhibitors were used to inhibit microglial BK channel based on their inhibitory kinetics. We previously identified that Ca2+‑activated K+ channel β3 auxiliary subunit (KCNMB3), which is an auxiliary subunit of BK channels and regulates gating properties of the channel, is exclusively expressed in microglia in the spinal cord. The present study analyzed the role of BK channels in spinal microglia in neuropathic pain using a spinal microglia‑specific BK channel knockdown method, with intrathecal injection of KCNMB3 small interfering RNA. Neuropathic pain was significantly attenuated in KCNMB3 knockdown mice. Increases in the number of microglia in the SDH following nerve injury were attenuated by KCNMB3 knockdown. Furthermore, increased levels of pain‑associated molecules in the SDH were attenuated in KCNMB3 knockdown mice. Attempts were also made to analyze the effects of KCNMB3 knockdown on chronic pain. KCNMB3 knockdown ameliorated chronic pain and inhibited the expression levels of pain‑associated molecules in the SDH. The results from the present study suggested that BK channels modulated the activation state of spinal microglia, and that KCNMB3 is a potential therapeutic target for neuropathic pain.
Learn More >To present data on psychometric properties of the Psychosocial Assessment Tool 2.0_General (PAT), a brief screener for psychosocial risk in families of youth with medical conditions, in youth with headache.
Learn More >Vinca alkaloids, thalidomide, and eribulin are widely used to treat patients with childhood acute lymphoblastic leukemia (ALL), adults affected by multiple myeloma and locally invasive or metastatic breast cancer, respectively. However, soon after their introduction into clinical practice, chemotherapy-induced peripheral neurotoxicity (CIPN) emerged as their main non-hematological and among dose-limiting adverse events. It is generally perceived that vinca alkaloids and the antiangiogenic agent thalidomide are more neurotoxic, compared to eribulin. The exposure to these chemotherapeutic agents is associated with an axonal, length-dependent, sensory polyneuropathy of mild to moderate severity, whereas it is considered that the peripheral nerve damage, unless severe, usually resolves soon after treatment discontinuation. Advanced age, high initial and prolonged dosing, coadministration of other neurotoxic chemotherapeutic agents and pre-existing neuropathy are the common risk factors. Pharmacogenetic biomarkers might be used to define patients at increased susceptibility of CIPN. Currently, there is no established therapy for CIPN prevention or treatment; symptomatic treatment for neuropathic pain and dose reduction or withdrawal in severe cases is considered, at the cost of reduced cancer therapeutic efficacy. This review critically examines the pathogenesis, epidemiology, risk factors (both clinical and pharmacogenetic), clinical phenotype and management of CIPN as a result of exposure to vinca alkaloids, thalidomide and its analogue lenalidomide as also eribulin.
Learn More >Herpes simplex virus-type 1 (HSV-1) infection of sensory neurons may lead to a significant reduction in the expression of voltage-activated Na and Ca channels, which can disrupt the transmission of pain information. Viral infection also results in the secretion of various pro-inflammatory cytokines, including interleukin (IL)-6. In this work, we tested whether IL-6 regulates the expression of Na and Ca channels post HSV-1 infection in ND7/23 sensory-like neurons. Our results demonstrate that HSV-1 infection causes a significant decrease in the protein expression of the Cav3.2 T-type Ca channel subunit, despite increasing Cav3.2 mRNA synthesis. Neither Cav3.2 mRNA nor total protein content was affected by IL-6 treatment post HSV-1 infection. In ND7/23 cells, HSV-1 infection caused a significant reduction in the expression of Na and T-type Ca channels within 48 h. Exposure of ND7/23 cells to IL-6 for 24 h post infection reverses the effect of HSV-1, resulting in a significant increase in T-type Ca current density. However, Na currents were not restored by 24 h-treatment with IL-6 post HSV-1 infection of ND7/23 cells. The ability of IL-6 to increase the functional expression of T-type Ca channels on the membrane was blocked by inhibition of protein trafficking with brefeldin-A and ERK1/2 activation. These results indicate that IL-6 release following HSV-1 infection regulates the expression of T-type Ca channels, which may alter the transmission of pain information. This article is protected by copyright. All rights reserved.
Learn More >MINI: In multivariate logistic regression analysis in 1,128 elderly people, NeP(+) (odds ratio (OR): 3.01), positive spinal inclination (OR: 1.14), and high VAS for LBP (OR: 1.04) were identified as risk factors for low physical QOL, and NeP(+) (OR: 5.32) was the only significant risk factor for low mental QOL.
Learn More >In previous studies that examined the impact of attention biases (ABs) on later pain outcomes, reaction times (RTs) in response to brief stimulus presentations had been used as measures of attention. Consequently, little is known about effects of ABs assessed during presentations of cues or biases in prolonged attention towards pain stimuli as influences on subsequent functioning. To address these gaps, 89 adults with chronic pain (68 women, 21 men) engaged in a baseline dot-probe task in which visual attention was tracked during injury-neutral (I-N) image pair presentations as well as a 6-month follow-up reassessing pain intensity and interference from pain. Neither RTs to probes after image pair offsets nor biases in initial orienting of gaze towards injury images predicted follow-up outcomes. However, participants who gazed at injury images for longer durations during I-N trials reported significantly more pain and interference at follow-up than did peers who gazed at injury images for less time, even after the impact of other significant baseline predictors had been controlled. In sum, results provided initial evidence for gaze biases reflecting prolonged vigilance towards pain-related information as a potential risk factor for relative elevations in pain and interference from chronic pain.
Learn More >In this multicenter cross-sectional study, we determined sensory profiles of patients with (NL-1) and without neuropathic pain (NL-0) after nerve lesion and assessed immune related systemic gene expression. Patients and matched healthy controls filled in questionnaires and underwent neurological examination, neurophysiological studies, quantitative sensory testing (QST), and blood withdrawal. Neuropathic pain was present in 67/95 (71%) patients (NL-1). Tactile hyperalgesia was the most prominent clinical sign in NL-1 patients (p<0.05). Questionnaires showed an association between neuropathic pain and the presence of depression, anxiety, and catastrophizing (p<0.05 to p<0.01). Neuropathic pain was frequently accompanied by other chronic pain (p<0.05). QST showed ipsilateral signs of small and large fiber impairment compared to the respective contralateral side, with elevated thermal and mechanical detection thresholds (p<0.001 to p<0.05) and lowered pressure pain threshold (p<0.05). Also, more loss of function was found in patients with NL-1 compared to NL-0. Pain intensity was associated with mechanical hyperalgesia (p<0.05 to p<0.01). However, QST did not detect or predict neuropathic pain. Gene expression of peptidylglycine α-amidating monooxygenase was higher in NL patients compared to healthy controls (NL-1, p<0.01; NL-0, p<0.001). Also, gene expression of tumor necrosis factor-α was higher in NL-1 patients compared to NL-0 (p<0.05), and interleukin-1ß was higher, but IL-10 lower in NL-1 patients compared to healthy controls (p<0.05 each). Our study reveals that nerve lesion presents with small and large nerve fiber dysfunction, which may contribute to the presence and intensity of neuropathic pain and which is associated with a systemic pro-inflammatory pattern.
Learn More >The current understanding of mechanisms behind migraine pain has been greatly enhanced with the recent therapies targeting calcitonin gene-related peptide and its receptor. The clinical efficacy of calcitonin gene-related peptide-blocking drugs indicates that, at least in a considerable proportion of patients, calcitonin gene-related peptide is a key molecule in migraine pain. There are several receptors and molecular pathways that can affect the release of and response to calcitonin gene-related peptide. One of these could be purinergic receptors that are involved in nociception, but these are greatly understudied with respect to migraine.
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