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People with type 2 diabetes (T2D) are more likely to develop a range of rheumatological and musculoskeletal symptoms (RMS), and experience both chronic and widespread pain, compared with the general population. However, these symptoms are not commonly acknowledged by researchers, which hampers our understanding of the impact on this population. Since exercise is a key lifestyle management strategy for T2D and participation levels are typically low, understanding the potential impact of RMS on exercise participation is critical. The aim of this review is to summarise the literature regarding the prevalence and pathophysiology of RMS in T2D, the evidence for the benefits and risks associated with exercise on RMS, and the currently available tools for the reporting of RMS in both research studies and community settings.
Relief of cancer-related pain remains challenging despite the availability of a range of opioid and non-opioid medications. Animal models demonstrate that T lymphocytes may mediate analgesia by producing endogenous opioids, but definitive clinical data are limited. Adoptive transfer of ex vivo activated T cell products (ACT) is being tested as an anti-cancer therapy. We retrospectively reviewed the medical charts of 357 patients with various malignancies who received three intravenous infusions of autologous cytokine-activated T cell-enriched products. Among these were fifty-five (55) patients who required opioids for moderate or severe cancer-related pain. Opioid dosage and cancer pain score were recorded daily for 2 consecutive weeks prior to and 2 weeks after the ACT infusions. The average oral morphine equivalent doses (OMED) and cancer pain scores were significantly decreased following the ACT infusions. The proportion of patients with breakthrough pain also declined. Moreover, higher frequencies of expanded CD3+, CD3+/CD4+, and CD3+/CD8+ T cells within the ACT product were associated with favorable analgesic effects. Transient elevations in CD3+ and CD3+/CD8+ T cell subpopulations and decreases in CD4CD25 Treg were observed in patients' blood after the ACT. In conclusion, ACT was capable of reducing cancer pain severity and opioid consumption and favorably modulating peripheral blood T cell populations.
Osteoarthritis is a common debilitating condition affecting a substantial portion of the population and is an accepted consequence of aging and over use. Whilst surgical interventions are a definitive approach, most cases are managed medically with analgesia. Pharmacological therapies have included acetaminophen, NSAIDs and opiates. Although significant controversies exist in the use of opioids for chronic musculoskeletal pain, many leading guidelines continue to recommend its use despite increasing evidence to suggest an increase in addiction, morbidity and mortality. With the opiate crisis growing, we re-examine the role opiates have in this chronic condition, current data and briefly evaluate alternative therapies.
Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment ("N-of-1 trial") on analgesic prescribing in patients with chronic musculoskeletal pain.
Pruritus is a major symptom of many inflammatory diseases and impacts greatly the quality of life in patients. We aimed to specify the characteristics of experimentally induced pruritus in normal skin and in experimentally induced inflammatory dermatitis in healthy volunteers.
To evaluate the anti-inflammatory and analgesic effect of sepiapterin reductase (SPR) inhibition in a mouse model of inflammatory joint disease and to evaluate sepiapterin as a non-invasive, translational biomarker of SPR inhibition/target engagement in mice and healthy human volunteers.
To review the published findings relevant to migraine and driving performance, with an intent to encourage discussion on research which may broaden understanding in this area and help educate healthcare providers and their patients.
Blood pressure (BP), pulse, electrocardiogram (ECG), and clinical cardiovascular (CV) outcomes in patients with episodic or chronic migraine treated for up to 6 months with galcanezumab compared to placebo were evaluated.
Meniere's disease (MD) is a chronic condition affecting the inner ear whose precise etiology is currently unknown. We propose the hypothesis that MD is a migraine-related phenomenon which may have implications for future treatment options for both diseases. The association between MD and migraine is both an epidemiological and a mechanistic one, with up to 51% of individuals with MD experiencing migraine compared to 12% in the general population. The presence of endolymphatic hydrops in those with MD may be the factor that unites the two conditions, as hydropic inner ears have an impaired ability to maintain homeostasis. Migraine headaches are theorized to cause aura and symptoms via spreading cortical depression that ultimately results in substance P release, alterations in blood flow, and neurogenic inflammation. Chronically hydropic inner ears are less able to auto-regulate against the changes induced by active migraine attacks and may ultimately manifest as MD. This same vulnerability to derangements in homeostasis may also explain the common triggering factors of both MD attacks and migraine headaches, including stress, weather, and diet. Similarly, it may explain the efficacy of common treatments for both diseases: current migraine treatments such as anti-hypertensives and anti-convulsants have shown promise in managing MD. Though the etiology of both MD and migraine is likely multifactorial, further exploration of the association between the two conditions may illuminate how to best manage them in the future. MD is likely a manifestation of cochleovestibular migraine, which occurs as a result of migraine related changes in both the cochlea and vestibule.
Adiponectin is an adipose tissue-derived cytokine that exerts its antiinflammatory effects by binding to 2 adiponectin receptors, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). However, the role of these adiponectin receptors on inflammatory pain remains unclear. We investigated the association between single nucleotide polymorphisms (SNPs) of these genes and inflammatory pain, such as postoperative pain and cancer pain.We analyzed 17 SNPs of the ADIPOR1 gene and 27 SNPs of the ADIPOR2 gene in 56 adult patients with postlaparotomy pain. We compared these genotypes with pain intensity and opioid consumption, adjusting for multiple testing. We analyzed the genotypes of 88 patients with cancer pain and examined the association of the relevant SNP(s) with pain intensity and opioid consumption.One variant of the ADIPOR1 gene (rs12045862) showed significant association with postoperative pain intensity; patients with minor allele homozygote (n = 7) demonstrated significantly worse pain intensity than that of combined patient group exhibiting major allele homozygote or the heterozygote (n = 49; Mann-Whitney test, P < .00002), although their opioid consumptions were comparable. Cancer pain intensity between minor allele homozygote patients (n = 7) and other 2 genotype patients (n = 81) were comparable.The rs12045862 SNP of the ADIPOR1 gene was associated with postoperative pain but not cancer pain. This might result from functional alteration of the ADIPOR1 signalling pathways, which influence the inflammatory process. ADIPOR1 may be a novel potential target for developing analgesics of postoperative pain.