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Migraine affects 28% of women in their pregnancy-capable years, and is associated with systemic inflammation, endothelial dysfunction, and increased risk of pregnancy-associated thromboembolic events. Migraine history has been associated with adverse pregnancy outcomes (APO) of placental origin, including hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). We tested the hypothesis that self-reported migraine in nulliparous individuals is associated with higher odds of APO.
Learn More >Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS).
Learn More >The objective of this study was to explore whether hypersensitivity in patients with subacromial pain syndrome manifests purely as localized peripheral sensitization or central sensitization, is influenced by the presence of subacromial pain, and presents similarly in male and female patients. Pressure pain threshold was assessed in both a patient cohort with unilateral subacromial pain syndrome and an uninjured matched control group. Control subjects were tested once, while patients were assessed at baseline and after an almost instantaneous reduction in pain arising from an anesthetic injection in patients. Patients received a subacromial injection consisting of both anesthetics (3 cc of 2% lidocaine and 6 cc 0.5% Marcaine with Epinephrine) and a corticosteroid agent (1 cc DepoMedrol). Patients demonstrated hypersensitivity across the involved shoulder only, providing evidence for peripheral sensitization. There were trends for hypersensitivity across remote joints, however when separated by sex, only female patients demonstrated both peripheral and central sensitization. Immediate pain reduction had no influence on hypersensitivity in the short-term. CLINICAL SIGNIFICANCE -: Neuropathic components are likely present in some patients with subacromial pain syndrome, and female patients may be particularly at risk for presenting with neuropathic pain. These findings are applicable towards understanding the heterogeneous etiology underlying subacromial pain syndrome and informing clinical management. This article is protected by copyright. All rights reserved.
Learn More >Anterior cruciate ligament (ACL) injury initiates a biochemical cascade thought to contribute to the onset and progression of posttraumatic osteoarthritis (PTOA). Interleukin-1ß (IL-1ß), IL-6, and C-telopeptide fragments of type II collagen (CTX-II) are implicated in joint inflammation and cartilage degradation following ACL injury; however, their association with pain is still being explored. The purpose of this study was to evaluate the associations between synovial fluid concentrations of IL-1ß, IL-6, and CTX-II with pain following ACL injury and reconstruction. We hypothesized that greater IL-1ß, IL-6, and CTX-II would correlate with greater Pain Visual Analogue Scale (VAS) scores. This was a secondary analysis of 23 patients (mean age=18.4 y, BMI=27.4, 13 Females/10 Males) with acute ACL tears who participated in a pilot randomized trial. Synovial fluid and VAS scores were collected on the day of initial presentation, at ACL reconstruction, and 1- and 4-weeks after surgery. Synovial fluid concentrations of IL-1ß, IL-6, and CTX-II were assessed using enzyme linked immunoabsorbent assays (ELISA), and repeated measures correlations were used to assess the relationships between pain and synovial IL-1ß, IL-6, or CTX-II after ACL injury and reconstruction. Pain was positively correlated with synovial fluid IL-6 concentrations (r=0.52, p<0.001); however, pain was inversely correlated with CTX-II (r= -0.39, p=0.002). IL-1ß had no significant correlation with pain. Statement of Clinical Relevance PTOA has been described as a "silent killer" and these results suggest that early PTOA may have pro-inflammatory pathways that are not primarily associated with pain but still lead to progressive cartilage loss. This article is protected by copyright. All rights reserved.
Learn More >Local anesthetics are commonly used for the management of intraoperative and postoperative acute and chronic pain caused by small invasive procedures. However, their short half-life and duration of action limit their clinical benefits. In this study, we proposed the incorporation of graphene oxide (GO) nanosheets to chitosan (CS)/β-glycerophosphate (GP) thermosensitive hydrogel system to form an injectable nanocomposite hydrogel (NCH) with improved mechanical properties and better control over the release of bupivacaine hydrochloride (BH). The prepared nanocomposite hydrogels were characterized for their gelation time, porosity, swelling ratio, injectability, mechanical strength and in vitro drug release. In vivo, the efficacy of the prepared NCH containing 0.5 % w/v BH was evaluated using a thermal nociceptive assay in a rat model. The incorporation of GO significantly enhanced the physicochemical and mechanical properties of the hydrogel scaffolds in a concentration-dependent manner. Inclusion of 0.1% w/v GO resulted in 84% reduction in gelation time and 16% and 40% decrease in the porosity and swelling ratio of the nanocomposite hydrogels, respectively. The mechanical strength of the CS/GP hydrogel scaffolds was also significantly improved in presence of GO. BH was slowly released from the NCHs containing 0.1% w/v GO and resulted in a 55% and 86.43% drug release after 6 and 24 h, respectively. In vivo studies showed that BH-loaded NCH significantly prolonged the local anesthetic effect and resulted in a 6.5-fold increase in blocking the pain sensory reflex compared to BH solution. These results indicate that the incorporation of GO significantly improved the physical and mechanical properties of CS/GP thermosensitive hydrogels and successfully sustained the effect of local anesthesia for more effective pain management.
Learn More >Type-2 cannabinoid receptors (CB2, encoded by the Cnr2 gene) are mainly expressed in immune cells, and CB2 agonists normally have no analgesic effect. However, nerve injury upregulates CB2 in the dorsal root ganglion (DRG), following which CB2 stimulation reduces neuropathic pain. It is unclear how nerve injury increases CB2 expression or how CB2 activity is transformed in neuropathic pain. In this study, immunoblotting showed that spinal nerve ligation (SNL) induced a delayed and sustained increase in CB2 expression in the DRG and dorsal spinal cord synaptosomes. RNAscope in situ hybridization also showed that SNL substantially increased CB2 mRNA levels, mostly in medium and large DRG neurons. Furthermore, we found that the specific CB2 agonist JWH-133 significantly inhibits the amplitude of dorsal root-evoked glutamatergic excitatory postsynaptic currents in spinal dorsal horn neurons in SNL rats, but not in sham control rats; intrathecal injection of JWH-133 reversed pain hypersensitivity in SNL rats, but had no effect in sham control rats. In addition, chromatin immunoprecipitation-qPCR analysis showed that SNL increased enrichment of two activating histone marks (H3K4me3 and H3K9ac) and diminished occupancy of two repressive histone marks (H3K9me2 and H3K27me3) at the Cnr2 promoter in the DRG. In contrast, SNL had no effect on DNA methylation levels around the Cnr2 promoter. Our findings suggest that peripheral nerve injury promotes CB2 expression in primary sensory neurons via epigenetic bivalent histone modifications and that CB2 activation reduces neuropathic pain by attenuating nociceptive transmission from primary afferent nerves to the spinal cord.
Learn More >To explore the ways in which stigma is experienced, and what strategies are used to manage stigma among patients using medical cannabis to ease suffering from chronic pain.
Learn More >Chronic pain conditions entail significant personal and societal burdens and improved outreach of evidence-based pain self-management programs are needed. Digital cognitive-behavioral self-management interventions have shown promise. However, evidence is still scarce and several challenges with such interventions for chronic pain exist. Exploring patients' experiences and engagement with digital interventions may be an essential step towards developing meaningful digital self-management interventions for those living with chronic pain.
Learn More >Migraine frequently is associated with White Matter Hyperintensities (WMHs). We aimed to assess the frequency of WMHs in migraine and to assess their risk factors.
Learn More >Information technology advances may help in conducting epidemiological studies using web-based surveys. Questionnaire-based headache diagnosis should be validated against the doctor's diagnosis. This study aimed to develop and validate a web-based diagnostic questionnaire for migraine, probable migraine (PM), and tension-type headache (TTH). We constructed a seven-item questionnaire for diagnosing migraine, PM, and TTH. A web-based survey was conducted among adults aged 20-59 years; migraine, PM, and TTH were diagnosed based on the responses. Validation interview was performed via telephone by a neurologist within 1 month after the web-based interview. Finally, 256 participants completed both web-based survey and validation interview. Of them, 121 (47.3%), 65 (25.4%), 61 (23.8%), and 9 (3.5%) were diagnosed with migraine, PM, TTH, and unclassified headache (UH), respectively in the web-based survey, whereas 119 (46.5%), 60 (23.4%), 74 (28.9%), 2 (0.8%), and 1 (0.4%) were diagnosed with migraine, PM, TTH, UH, and primary stabbing headache, respectively in the validation interview. The best agreement was found in migraine (sensitivity: 92.6%; specificity: 94.8%; kappa coefficient: 0.875), followed by TTH (sensitivity: 78.4%; specificity: 98.4%; kappa coefficient: 0.809). PM showed the least agreement (sensitivity: 85.0%; specificity: 92.9%; kappa coefficient: 0.757). In conclusion, our questionnaire is valid in identifying these headache disorders.
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