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The roles of the hypothalamus and particularly the lateral hypothalamus (LH) in the regulation of inflammation and pain have been widely studied. The LH consists of a parasympathetic area that has connections with all the major parts of the brain. It controls the autonomic nervous system (ANS), regulates feeding behavior and wakeful cycles, and is a part of the reward system. In addition, it contains different types of neurons, most importantly the orexin neurons. These neurons, though few in number, perform critical functions such as inhibiting pain transmission and interfering with the reward system, feeding behavior and the hypothalamic pituitary axis (HPA). Recent evidence has identified a new role for orexin neurons in the modulation of pain transmission associated with several inflammatory diseases, including rheumatoid arthritis and ulcerative colitis. Here, we review recent findings on the various physiological functions of the LH with special emphasis on the orexin/receptor system and its role in mediating inflammatory pain.
Learn More >The opioid family of GPCRs consists of the classical opioid receptors, designated μ-, κ-, and δ-opioid receptors, and the orphanin-FQ receptor, and these proteins are expressed on both neuronal and hematopoietic cells. A number of laboratories have reported that an important degree of cross-talk can occur between the opioid receptors and the chemokine and chemokine receptor families. As a part of this, the opioid receptors are known to regulate the expression of certain chemokines and chemokine receptors, including those that possess strong pro-inflammatory activity. At the level of receptor function, it is clear that certain members of the chemokine family can mediate cross-desensitization of the opioid receptors. Conversely, the opioid receptors are all able to induce heterologous desensitization of some of the chemokine receptors. Consequently, activation of one or more of the opioid receptors can selectively cross-desensitize chemokine receptors and regulate chemokine function. These cross-talk processes have significant implications for the inflammatory response, since the regulation of both the recruitment of inflammatory cells, as well as the sensation of pain, can be controlled in this way.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
Learn More >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.
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