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People with chronic pain report experiencing stigma, but few studies have explored this in detail. This mixed-methods study aimed to investigate factors that contribute to chronic pain stigma, the effects of stigma, and to explore the stigma experiences of people with chronic pain. Participants were 215 adults with chronic pain who completed questionnaires assessing chronic pain stigma, opioid use, mental health conditions, pain, depression, disability and social support, and 179 also answered open-ended questions about stigma experiences. Linear regression and path analysis showed that greater stigma was experienced by those who used more opioids, had a mental health condition, viewed their pain as organic, and were unemployed. Stigma was associated with greater disability, depression and lower social support. Qualitative results supported quantitative findings, with 3 themes: 1. "Faking It": Others disbelieve pain and attribute it to drug seeking, laziness, or mental health problems, 2. A spectrum of stigma: Experiences of stigma vary from none to widespread, and 3. "I hide it well": Concealing pain and avoiding stigmatizing situations lead to isolation & disability. This study demonstrates the negative influence of stigma and presents a novel integrated model of chronic pain stigma which may be used to develop interventions.
Learn More >Chronic triptan exposurein rodents recapitulates medication overuse headache (MOH), causing cephalic pain sensitization and trigeminal ganglion overexpression of pronociceptive proteins including CGRP. Because of these transcriptional derangements, as well as the emerging role of epigenetics in chronic pain, in the present study, we evaluated the effects of the histone deacetylase inhibitors (HDACis) panobinostat and givinostat, in rats chronically exposed to eletriptan for one month. Both panobinostat and givinostat counteracted overexpression of genes coding for CGRP and its receptor subunit RAMP1, having no effects on CLR and RCP receptor subunits in the trigeminal ganglion (TG) of eletriptan-exposed rats. Within the trigeminal nucleus caudalis (TNc), transcripts for these genes were neither upregulated by eletriptan nor altered by concomitant treatment with panobinostat or givinostat. HDACis counteracted hypersensitivity to capsaicin-induced vasodilatation in the trigeminal territory, as well as photophobic behavior and cephalic allodyniain eletriptan-exposed rats. Eletriptan did not affect CGRP, CLR, and RAMP1 expression in cultured trigeminal ganglia, whereas both inhibitors reduced transcripts for CLR and RAMP-1. The drugs, however, increased luciferase expression driven by CGRP promoter in cultured cells. Our findings provide evidence for a key role of HDACs and epigenetics in MOH pathogenesis, highlighting the therapeutic potential of HDAC inhibition in the prevention of migraine chronification.
Learn More >Microglia, the dynamic innate immune cells of the central nervous system, become activated in epilepsy. The process of microglial activation in epilepsy results in the creation of an inflammatory environment around the site of seizure onset, which contributes to the epileptogenic process and epilepsy progression. Cannabidiol (CBD) has been effective for use as an adjunctive treatment for two severe pediatric seizure disorders. Newly recognized as an Food and Drug Administration (FDA)-approved drug treatment in epilepsy, it has gained in popularity primarily for pain management. Although CBD is readily available in stores and online retailers, its mechanism of action and specifically its effects on microglia and their functions are yet fully understood. In this study, we examine the effects of commercially available CBD on microglia inflammatory activation and neurogenic response, in the presence and absence of seizures. We use systemic administration of kainate to elicit seizures in mice, which are assessed behaviorally. Artisanal CBD is given in different modes of administration and timing to dissect its effect on seizure intensity, microglial activation and aberrant seizure-related neurogenesis. CBD significantly dampens microglial migration and accumulation to the hippocampus. While long term artisanal CBD use does not prevent or lessen seizure severity, CBD is a promising adjunctive partner for its ability to depress epileptogenic processes. These studies indicate that artisanal CBD is beneficial as it both decreases inflammation in the CNS and reduces the number of ectopic neurons deposited in the hippocampal area post seizure.
Learn More >Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca efflux as a pathway underlying temporal summation and persistent pain, which may be amenable to therapeutic targeting.
Learn More >Spinal cord stimulation (SCS) is a treatment for chronic neuropathic pain. It is based on the delivery of electric impulses to the spinal cord, traditionally in a regular square-wave pattern ("tonic" stimulation) and, more recently, in a rhythmic train-of-five "BurstDR" pattern. The safety of active SCS therapy in pregnancy is not established, and recommendations are based on limited casuistic evidence. We present in this study clinical data on a case series of six women treated with burst SCS during pregnancy. In addition, we present the ultrasonographic flow measurements of fetal and uteroplacental blood flow in a pregnant patient.
Learn More >Pre-clinical studies demonstrate opposing effects of long-chain polyunsaturated fatty acid (PUFA) metabolites on inflammation and nociception. Omega-6 (n-6) PUFAs amplify both processes while omega-3 (n-3) PUFAs inhibit them. This cross-sectional study examined relationships between PUFAs in circulating erythrocytes and two chronic idiopathic pain conditions: temporomandibular disorder (TMD) and low back pain in a community-based sample of 503 U.S. adults. Presence or absence of TMD and low back pain, respectively, were determined by clinical examination and by responses to established screening questions. Liquid chromatography tandem mass spectrometry quantified PUFAs. In multivariable logistic regression models, a higher ratio of n-6/n-3 long-chain PUFAs was associated with greater odds of TMD (odds ratio ((OR)=1.75, 95% confidence limits (CL): 1.16, 2.64) and low back pain (OR=1.63, 95% CL: 1.07, 2.49). Higher levels of the pronociceptive n-6 long-chain arachidonic acid were associated with greater probability of both pain conditions for women, but not men. Higher levels of the antinociceptive long-chain n-3 PUFAs eicosapentaenoic and docosahexaenoic acids were associated with lower probability of both pain conditions for men, but not women. As systemic inflammation is not a hallmark of these conditions, PUFAs may influence idiopathic pain through other mechanisms.
Learn More >Bone is the preferential site of metastasis for breast cancer. Invasion of cancer cells induces the destruction of bone tissue and damnification of peripheral nerves and consequently induced central sensitization which contributes to severe pain. Herein, cancer induced bone pain (CIBP) rats exhibited destruction of tibia, mechanical allodynia and spinal inflammation. Inflammatory response mainly mediated by astrocyte and microglia in central nervous system. Our immunofluorescence analysis revealed activation of spinal astrocytes and microglia in CIBP rats. Transmission electron microscopy (TEM) observations of mitochondrial outer membrane disruption and cristae damage in spinal mitochondria of CIBP rats. Proteomics analysis identified abnormal expression of proteins related to mitochondrial organization and function. Intrathecally, injection of GSK-3β activity inhibitor TDZD-8 significantly attenuated Drp1-mediated mitochondrial fission and recovered mitochondrial function. Inhibition of GSK-3β activity also suppressed NLRP3 inflammasome cascade and consequently decreased mechanical pain sensitivity of CIBP rats. For cell research, TDZD-8 treatment significantly reversed TNF-α induced mitochondrial membrane potential (MMP) deficiency and high mitochondrial reactive oxygen species level. Taken together, GSK-3β inhibition by TDZD-8 decreases spinal inflammation and relieves cancer induced bone pain via reducing Drp1-mediated mitochondrial damage.
Learn More >Chronic migraine (CM) is a great challenge for physicians dealing with headaches. Despite the introduction of the monoclonal antibodies (mAbs) acting against the calcitonin gene-related peptide (CGRP) that has revolutionized the treatment of CM, some patients still experience an incomplete relief. So, the association of two preventive treatments may be a reliable option for these patients. So, onabotulinumtoxinA (BT-A) and anti-CGRP mAbs may be used together, and some pre-clinical and clinical evidence of an additive action of the 2 drugs is emerging. In particular, since BT-A acts mainly on C-fibers and anti-CGRP mAbs on Aδ ones, their association may prevent the wearing-off phenomenon of BT-A, thus giving an additional benefit in those patients experiencing an incomplete response to BT-A alone. Despite this, the clinical studies available in the literature have a small sample size, often a retrospective design, and are heterogeneous in terms of the outcomes chosen. Considering this, the evidence of a favorable effect of the association between BT-A and anti-CGRP mAbs is still scarce. Furthermore, this association is explicitly forbidden by many National regulatory agencies, due to the high costs of both treatments. Anyway, their association could help in reducing the burden associated with the most severe cases of CM, thus relieving the direct and indirect costs of this condition. More well-designed studies with big samples are needed to unveil the real therapeutic gain of this association. Moreover, pharmacoeconomics studies should be performed, to assess the economic suitability of this association.
Learn More >There has been a sparse exploration of the lived experience of men with urologic chronic pelvic pain syndrome (UCPPS), and none with the goal of Investigating the experience of "flares" as part of this chronic pain syndrome in men.
Learn More >To investigate the long-term effects of motor cortex stimulation (MCS) on central poststroke pain (CPSP) in patients with thalamic and extrathalamic stroke.
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