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Neuronal activity can be modulated by mechanical stimuli. To study this phenomenon quantitatively, we mechanically stimulated rat cortical neurons by shear stress and local indentation. Neurons show 2 distinct responses, classified as transient and sustained. Transient responses display fast kinetics, similar to spontaneous neuronal activity, whereas sustained responses last several minutes before returning to baseline. Local soma stimulations with micrometer-sized beads evoke transient responses at low forces of ∼220 nN and pressures of ∼5.6 kPa and sustained responses at higher forces of ∼360 nN and pressures of ∼9.2 kPa. Among the neuronal compartments, axons are highly susceptible to mechanical stimulation and predominantly show sustained responses, whereas the less susceptible dendrites predominantly respond transiently. Chemical perturbation experiments suggest that mechanically evoked responses require the influx of extracellular calcium through ion channels. We propose that subtraumatic forces/pressures applied to neurons evoke neuronal responses via nonspecific gating of ion channels.
Learn More >Codeine is one of the most common opioid medicines for treating pain. Australia introduced policy changes in February 2018 to up-schedule codeine to prescription-only medicine due to concerns of adverse effects, opioid dependency and overdose-related mortality. This study investigated the frequency and content of messages promoted on Twitter by four Australian peak pain organizations, pre- and post-policy implementation. A time series analysis examined frequency of Twitter posts over a 48-week period. Text analysis via Leximancer examined message content. Results showed that promotion and education of the pending policy change dominated the Twitter feed prior to up-scheduling. However, immediately following policy change, there was a shift in content towards promoting conferences and research, and a significant decrease in the frequency of codeine-related posts, compared to opioid-related non-codeine posts. The findings suggest that pain organizations can provide timely and educational policy dissemination in the online environment. They have implications for individuals with chronic pain who use the Internet for health information and the degree to which they can trust these sources, as well as health professionals. Further research is required to determine if public health campaigns can be targeted to prevent opioid-related harm and improve pain care via this increasingly used medium. Perspective: This study presents a first look at what information is being communicated by influential pain organizations who have an online Twitter presence and how messages were delivered during a major policy change restricting access to codeine medicines. Insights could drive targeted future online health campaigns for improved pain management.
Learn More >The purpose of the study was to explore clinical management for new cases of musculoskeletal pain that are likely chronic. We used data from the National Ambulatory Medical Care Survey, 2007-2015, identifying visits with a new chronic musculoskeletal pain condition using pre-determined ICD-9 codes. We documented prescribing of non-opioid pain medication, opioids, physical therapy (PT), counseling, and other nonpharmacologic treatments and explored associations between patient and provider factors for each of these treatments. There were 111,994 visits over the 9-year period for a new case of chronic musculoskeletal pain, representing an average of 36.8 million weighted visits per year or approximately 11.8% of the population. Proportions that were prescribed nonopioid medication, opioids, PT, counseling and other nonpharmacologic treatments were: 40.2, 21.5, 10.0, 15.2 and 14.3 respectively. Patient age was associated with type of treatment with a young to old gradient for other nonpharmacologic treatments, PT, opioids, counseling and other medications. Orthopedists were less likely to prescribe pharmacological treatments than family practice physicians and more likely to prescribe PT. Physicians who used the electronic medical record were more likely to prescribe opioids. Contrary to practice guidelines for managing musculoskeletal pain, many patients are prescribed opioids for a new chronic musculoskeletal problem. PERSPECTIVE: We outlined in a representative sample of Americans what treatments are being prescribed for new cases of likely chronic musculoskeletal pain. Opioid prescription was double that of physical therapy. Using the electronic medical record was associated with more opioid prescription- a novel finding that should be corroborated by future research.
Learn More >The pathophysiology of pediatric musculoskeletal (MSK) pain is unclear, contributing to persistent challenges to its management.
Learn More >The ability of clinical trials to inform the care of chronic pain may be limited if only an unrepresentative subset of patients are allowed to enroll. We summarize and report new insights on published studies that report on how trial exclusions affect the generalizability of their results. We conducted a PubMed search on the following terms: (("eligibility criteria" AND generalizability) OR ("exclusion criteria" AND generalizability) OR "exclusion criteria"[ti] OR "eligibility criteria"[ti]) AND pain. We only considered studies relevant if they analyzed data on (1) the prevalence and nature of exclusion criteria or (2) the impact of exclusion criteria on sample representativeness or study results. The 4 articles that were identified reported differences in patients who were included and excluded in different clinical trials: excluded patients were older, less likely to have a paid job, had more functional limitations at baseline, and used strong opioids more often. The clinical significance of these differences remains unclear. The pain medicine literature has very few published studies on the prevalence and impact of exclusion criteria, and the outcomes of excluded patients are rarely tracked. The frequent use of psychosocial exclusions is especially compromising to generalizability because chronic pain commonly co-occurs with psychiatric comorbidities. Inclusion of more representative patients in research samples can reduce recruitment barriers and broaden the generalizability of findings in patients with chronic pain. We also call for more studies that examine the use of exclusion criteria in chronic pain trials to better understand their implications.
Learn More >Chronic low back pain (cLBP) is highly prevalent in the United States and globally, resulting in functional impairment and lowered quality of life. While many treatments are available for cLBP, clinicians have little information about which specific treatment(s) will work best for individual patients or subgroups of patients. The Back Pain Research Consortium, part of the National Institutes of Health Helping to End Addiction Long-term (HEAL) Initiative, will conduct a collaborative clinical trial, which seeks to develop a personalized medicine algorithm to optimize patient and provider treatment selection for patients with cLBP.
Learn More >: Fitzcharles M-A, Cohen SP, Clauw DJ, Littlejohn G, Usui C, Häuser W. Chronic primary musculoskeletal pain: a new concept of non-structural regional pain. PAIN Reports 2022;7:e1024. : Treede R-D. Chronic musculoskeletal pain: traps and pitfalls in classification and management of a major global disease burden. PAIN Reports 2022;7:e1023.
Learn More >MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate TRX-Induced PHN in Mice.
Varicella zoster virus-induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by TRX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were decreased in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate TRX-induced PHN in mice.
Learn More >Preliminary clinical studies on medical cannabis (MC) treatment using the Syqe Inhaler showed short-term effectiveness and safety at very low and precise doses of MC.
Learn More >Altered pain facilitatory and inhibitory mechanisms have been recognized as an important manifestation in patients with chronic pain, and quantitative sensory testing (QST) can act as a proxy for this process. We have recently developed a simple bedside QST tool kit () for more clinical use. The purpose of this study was to investigate its test-retest reliability and to evaluate its validity compared with the laboratory-based QST protocols in patients with knee osteoarthritis (OA).
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