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Sex differences in gene expression are important contributors to normal physiology and mechanisms of disease. This is increasingly apparent in understanding and potentially treating chronic pain where molecular mechanisms driving sex differences in neuronal plasticity are giving new insight into why certain chronic pain disorders preferentially affect women vs. men. Large transcriptomic resources are now available and can be used to mine for sex differences to gather insight from molecular profiles using donor cohorts. We performed in-depth analysis of 248 human tibial nerve (hTN) transcriptomes from the GTEx Consortium project to gain insight into sex-dependent gene expression in the peripheral nervous system (PNS). We discover 149 genes with sex differential gene expression. Many of the more abundant genes in men are associated with inflammation and appear to be primarily expressed by glia or immune cells, with some genes downstream of Notch signaling. In women, we find the differentially expressed transcription factor SP4 that is known to drive a regulatory program, and may impact sex differences in PNS physiology. Many of these 149 differentially expressed (DE) genes have some previous association with chronic pain but few of them have been explored thoroughly. Additionally, using clinical data in the GTEx database, we identify a subset of DE, sexually dimorphic genes in diseases associated with chronic pain: arthritis and Type II diabetes. Our work creates a unique resource that identifies sexually dimorphic gene expression in the human PNS with implications for discovery of sex-specific pain mechanisms.
Learn More >Pain is highly prevalent in patients with Parkinson's disease (PD), but underlying pathophysiological mechanisms are largely unclear. Alterations in somatosensory processing might contribute to sensory abnormalities in PD.
Learn More >Previous studies have shown the efficacy of tapentadol (TP) for chronic cancer pain. We evaluated multiple effectiveness aspects of TP prolonged release on moderate-severe cancer-related pain, neuropathic pain (NeP), patient satisfaction, and quality of life.
Learn More >It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM). In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus. EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm, =0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm, =0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm, =0.030 and 2.30±0.46 versus 1.63±0.52, =0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients. The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.
Learn More >To investigate the prevalence of anxiety, depression and mixed anxiety and depressive disorder (MADD) and factors associated with these conditions in women with chronic pelvic pain (CPP) compared to a pain-free control group. A cross-sectional study was conducted with 100 women with CPP and 100 without CPP. The Hospital Anxiety and Depression Scale (HADS) was used to evaluate the presence of anxiety and depression. Sociodemographic, behavioral and clinical characteristics were investigated. Fisher's exact test was used to compare characteristics between groups. A log-binomial regression model was used, with adjustment for age, skin color, schooling, body mass index and pain. Prevalence ratios (PR), together with their 95% confidence intervals (CI), were calculated to investigate factors associated with anxiety, depression and MADD. The prevalence of anxiety was 66% in the CPP group and 49% in the controls (=0.02). Depression was identified in 63% of the women with CPP and in 38% of the controls (<0.01). MADD was present in 54% of the CPP group and in 28% of the controls (<0.01). In the adjusted analysis, CPP (PR=1.3; 95%CI: 1.1-1.6), physical abuse (PR=1.5; 95%CI: 1.2-1.8) and sexual abuse (PR=1.5; 95%CI: 1.1-1.8) were independently associated with anxiety. Women of 25 to 34 years of age were less likely to have anxiety (PR=0.6; 95%CI: 0.4-0.8). CPP (PR=1.6; 95%CI: 1.2-2.2), physical abuse (PR=1.3; 95%CI: 1.1-1.7) and sexual abuse (PR=1.7; 95%CI: 1.3-2.2) were independently associated with depression. CPP (PR=1.9; 95%CI: 1.3-2.7), smoking (PR=1.5; 95%CI: 1.1-2.1), physical abuse (PR=1.4; 95%CI: 1.1-1.9) and sexual abuse (PR=1.4; 95%CI: 1.1-1.8) were independently associated with MADD. The prevalence of anxiety, depression and MADD was higher in women with CPP compared to the pain-free controls. Factors associated with mental disorders were identified. The independent association between CPP and anxiety, depression and MADD was noteworthy. These findings suggest that systematic management of psychological factors could contribute towards improving the mental health of these women.
Learn More >This study reports on physicians' experiences with chronic pain management. For over a decade prescription opioids have been a primary treatment for chronic pain in North America. However, the current opioid epidemic has complicated long-standing practices for chronic pain management which historically involved prescribing pain medication. Caring for patients with chronic pain occurs within a context in which a growing proportion of patients suffer from chronic rather than acute conditions alongside rising social inequities.
Learn More >This study evaluates the reporting quality of randomized controlled trials (RCTs) on acupuncture use for the treatment of postherpetic neuralgia and explores related factors.
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