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Fibromyalgia, a complex disorder that affects 1% to 5% of the population, presents as widespread chronic musculoskeletal pain without physical or laboratory signs of any specific pathologic process. The mechanism, while still being explored, suggests central sensitization and disordered pain regulation at the spinal cord and supraspinal levels, with a resulting imbalance between excitation and inhibition that may alter central nervous system nociceptive processing. Nociceptive hypersensitivity results from activity of the N-methyl-D-aspartate receptor (NMDAR)-mediated glutamatergic synaptic transmission in the spinal cord and brain. Because ketamine, an NMDAR antagonist, may reduce induction of synaptic plasticity and maintenance of chronic pain states, the study of its use in intravenous form to treat fibromyalgia has increased. We conducted a literature search with the objectives of examining the effect of intravenous ketamine administration on pain relief, identifying side effects, and highlighting the need for clinical studies to evaluate ketamine infusion treatment protocols for patients with fibromyalgia. We used the keywords "fibromyalgia," "chronic pain," "ketamine," "intravenous," and "infusion" and found 7 publications that included 118 patients with fibromyalgia who met inclusion criteria. Clinical studies revealed a short-term reduction-only for a few hours after the infusions-in self-reported pain intensity with single, low-dose, intravenous ketamine infusions, likely attributable to nociception-dependent central sensitization in fibromyalgia via NMDAR blockade. Case studies suggest that increases in the total dose of ketamine and longer, more frequent infusions may be associated with more effective pain relief and longer-lasting analgesia. Another neurotransmitter release may be contributing to this outcome. This systematic review suggests a dose response, indicating potential efficacy of intravenous ketamine in the treatment of fibromyalgia.
Learn More >Itch occurs in various dermatologic and systemic conditions. Many patients report that certain foods instigate itch, although there is limited published information in dermatology on food-induced pruritus. In addition, itch severity is rarely mentioned. Food can induce pruritus through either ingestion or direct contact with skin or mucosal membranes. The most common type of itch provoked by food is acute urticaria, often through the classical immunoglobulin E (IgE)-mediated pathway. Other mechanisms include non-IgE-mediated, mixed (IgE-mediated and non-IgE-mediated), T-cell-mediated, and nonimmune reactions. For patients presenting with urticaria, generalized pruritus, oral pruritus, or dermatitis, a thorough history is warranted, and possible food associations should be considered and assessed. Although any food seems to have the potential to elicit an immune response, certain foods are especially immunogenic. Treatment includes avoidance of the trigger and symptom management. Careful consideration should be used as to avoid unnecessarily restrictive elimination diets.
Learn More >Chronic pain is treated with multimodal rehabilitation programs, targeting improvement in several health aspects. These treatments must be evaluated multidimensionally, which is a methodological challenge.
Learn More >Calpain I is a calcium-dependent cysteine protease which has dual effects on tissue inflammation depending on its cellular location. Intracellularly, calpain I has pro-inflammatory properties but becomes anti-inflammatory when exteriorised into the extracellular space. In this study, the effect of calpain I on joint pain was investigated using the kaolin/carrageenan model of acute synovitis. Evoked pain behaviour was determined by von Frey hair algesiometry and non-evoked pain was measured using dynamic hindlimb weight bearing. Local administration of calpain I reduced secondary allodynia in the acute inflammation model and this effect was blocked by the cell impermeable calpain inhibitor E-64c. Calpain I also blocked the algesic effect of the protease activated receptor-2 (PAR-2) cleaving enzyme mast cell tryptase. The cell permeable calpain blocker E-64d also produced analgesia in arthritic joints. These data suggest that calpain I produces disparate effects on joint pain . analgesia when present extracellularly by disarming PAR-2, and pro-algesic when the enzyme is inside the cell.
Learn More >Patients suffering from fibromyalgia syndrome (FMS) are heterogenous. They often present with sensory abnormalities and comorbidities.
Learn More >Chronic low back pain (CLBP) is often treated with opioid analgesics (OA), a class of medications associated with a significant risk of misuse. However, little is known about how treatment with OA affect the brain in chronic pain patients. Gaining this knowledge is a necessary first step towards understanding OA associated analgesia and elucidating long-term risk of OA misuse. Here we study CLBP patients chronically medicated with opioids without any evidence of misuse and compare them to CLBP patients not on opioids and to healthy controls using structural and functional brain imaging. CLBP patients medicated with OA showed loss of volume in the nucleus accumbens and thalamus, and an overall significant decrease in signal to noise ratio in their sub-cortical areas. Power spectral density analysis (PSD) of frequency content in the accumbens' resting state activity revealed that both medicated and unmedicated patients showed loss of PSD within the slow-5 frequency band (0.01-0.027 Hz) while only CLBP patients on OA showed additional density loss within the slow-4 frequency band (0.027-0.073 Hz). We conclude that chronic treatment with OA is associated with altered brain structure and function within sensory limbic areas.
Learn More >Psychologically informed physical therapy (PIPT) blends psychological strategies within a physical therapist's treatment approach for the prevention and management of chronic musculoskeletal pain. Several randomized trials have been conducted examining the efficacy of PIPT compared to standard physical therapy on important patient-reported outcomes of disability, physical function, and pain. In this review, we examine recent trials published since 2012 to describe current PIPT methods, discuss implications from findings, and offer future directions. Twenty-two studies, representing 18 trials, were identified. The studied PIPT interventions included (1) graded activity or graded exposure (n = 6), (2) cognitive-behavioral-based physical therapy (n = 9), (3) acceptance and commitment-based physical therapy (n = 1), and (4) internet-based psychological programs with physical therapy (n = 2). Consistent with prior reviews, graded activity is not superior to other forms of physical activity or exercise. In a few recent studies, cognitive-behavioral-based physical therapy had short-term efficacy when compared to a program of standardized exercise. There is a need to further examine approaches integrating alternative strategies including acceptance-based therapies (ie, acceptance and commitment therapy or mindfulness) or internet-based cognitive-behavioral programs within physical therapy. Although PIPT remains a promising care model, more convincing evidence is needed to support widespread adoption, especially in light of training demands and implementation challenges.
Learn More >Nociceptor sensory neurons innervate barrier tissues that are constantly exposed to microbial stimuli. During infection, pathogenic microorganisms can breach barrier surfaces and produce pain by directly activating nociceptors. Microorganisms that live in symbiotic relationships with their hosts, commensals and mutualists, have also been associated with pain, but the molecular mechanisms of how symbionts act on nociceptor neurons to modulate pain remain largely unknown. In this review, we will discuss the known molecular mechanisms of how microbes directly interact with sensory afferent neurons affecting nociception in the gut, skin and lungs. We will touch on how bacterial, viral and fungal pathogens signal to the host to inflict or suppress pain. We will also discuss recent studies examining how gut symbionts affect pain. Specifically, we will discuss how gut symbionts may interact with sensory afferent neurons either directly, through secretion of metabolites or neurotransmitters, or indirectly,through first signaling to epithelial cells or immune cells, to regulate visceral, neuropathic and inflammatory pain. While this area of research is still in its infancy, more mechanistic studies to examine microbial-sensory neuron crosstalk in nociception may allow us to develop new therapies for the treatment of acute and chronic pain.
Learn More >Diagnostic uncertainty (DU), which is the perception that a label or explanation for a patient's health problem is missing or inaccurate, has been linked to distress, anxiety, and difficulty coping among adults with pain. This study examined the prevalence of DU among youth with chronic pain and their parents and the relation of parent and youth DU with youth pain, pain-related constructs, and health-related quality of life (HRQoL).
Learn More >Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with ( = 20) and without ( = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (s ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions.
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