Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies, and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type-specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3 1/2 months after the initial injury. This raises the question of whether the commonly used categorisation of pain into “inflammatory” and “neuropathic” is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq data sets on neurons, macrophages, and Schwann cells in naive and nerve injury states. The result is a practical web-based tool for the transcriptional data mining of peripheral neuroimmune interactions. http://rna-seq-browser.herokuapp.com/
Correct communication between immune cells and peripheral neurons is crucial for the protection of our bodies. Its breakdown is observed in many common, often painful conditions, including arthritis, neuropathies and inflammatory bowel or bladder disease. Here, we have characterised the immune response in a mouse model of neuropathic pain using flow cytometry and cell-type specific RNA sequencing (RNA-seq). We found few striking sex differences, but a very persistent inflammatory response, with increased numbers of monocytes and macrophages up to 3½ months after the initial injury. This raises the question of whether the commonly used categorisation of pain into "inflammatory" and "neuropathic" is one that is mechanistically appropriate. Finally, we collated our data with other published RNA-seq datasets on neurons, satellite glial cells, macrophages and Schwann cells in naïve and nerve injury states. The result is a practical web-based tool for the transcriptional data-mining of peripheral neuroimmune interactions. Figure 8: At one week post PSNL, MHCII+/Ly6C-myeloid cells from sciatic nerve upregulate functions relating to interactions with other immune cells, in favour of more generic pro-inflammatory and homeostatic activities.A) STRING network analysis reveals that 77 of 186 genes upregulated in ipsilateral MHCII+ macrophages at adj. p < 0.05 are likely to be functionally connected with overrepresented processes including antigen presentation, regulation of lymphocytes and myeloid cell activation. B) Conversely, 41 of 93 significantly downregulated genes formed a network that includes transcripts relating to pro-inflammatory function (TNF, complements), regulation of angiogenesis and canonical macrophage markers, like CD163 typically found in resident macrophages. See Suppl. Table 5 for differential expression tables.
Acetaminophen is one of the most commonly consumed analgesics world wide. Generally perceived as a safe medication, it is the most common cause of acute liver failure in the United States with inadvertent hepatotoxicity in half of all cases. We therefore conducted a survey on the public perceptions of acetaminophen in patients attending the outpatient clinic in Vancouver, Canada. Among 928 patients who were asked, 765 completed the survey questionnaire. The majority of respondents were female (59%), Caucasian (61%), and educated beyond the secondary school level (81%). 23% reported using acetaminophen at least once a week. A significant minority were unaware of the potential liver toxicity of acetaminophen (24%), and knowledge of hepatotoxicity did not vary with education status. In terms of the medicinal composition of acetaminophen products, over half of the respondents (58%) did not know that extra strength preparations of acetaminophen contained the same drug but in a different dose. This knowledge was more prevalent among those with higher level of education (49% in graduate school educated respondents), but was still low overall. The knowledge that alcohol use with acetaminophen was more harmful was low (43%), but improved with level of education (P for trend 0.03). Among respondents who consumed alcohol regularly, 21% were consuming over 1.5 grams of acetaminophen at a time. These patients had similar harm perception to liver as patients who consumed lower doses of acetaminophen. Overall, in a large, well-educated cohort of patients, knowledge about the adverse effects of acetaminophen, the additional risks with alcohol and composition of various retailed products was suboptimal. We speculate that consumer ignorance is a significant reason why acetaminophen is a leading cause of acute liver failure.
Objective The COVID-19 pandemic necessitated changes in the delivery of ambulatory care for patients with inflammatory bowel disease (IBD), including transitioning many visits to virtual formats and delaying non-urgent assessments. We aimed to evaluate the impact of the COVID-19 pandemic on IBD patient care from health care providers’ (HCP) and patients’ perspectives. Methods We administered a 42-question HCP survey and a 44-question patient survey, which evaluated HCP and patient experience and satisfaction with care delivery and delays in access to IBD care during the first wave of the COVID-19 pandemic. Results Surveys were completed by 19.2% (24/125) HCPs and 25.8% (408/1581) patients. Overall, 82.7% of patients with IBD maintained their care without disruption. The majority of patients were satisfied with a transition to virtual care. All HCPs were willing to use virtual care in the future; however, 60% (14/24) of HCPs reported that virtual care was not equivalent to in-person visits. Patients reported concerns around access to health resources, the uncertainty of IBD-specific care, and fear and stress due to employment uncertainty and safety. Providers also reported concerns about patient safety, patient education, adequate remuneration and challenges with providing care for new patients on virtual platforms. Conclusion While some delays in health care delivery occurred during the first wave of the pandemic, both patients and HCPs were satisfied with a transition to new models of care delivery. These models may remain in place post-pandemic and allow for flexibility in care delivery that is acceptable to both patients and HCPs.
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