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Guidelines recommend a number of pharmacotherapeutic options used as monotherapy or in combination with others for treating the pain of trigeminal neuropathy.
Learn More >This multicenter cohort study investigated the prevalence of musculoskeletal post-COVID pain during the first year after the infection with mosaic plots and an exponential bar plot model and its associated risk factors. Patients hospitalized because of COVID-19 in 5 hospitals of Madrid (Spain) were scheduled for a telephone interview at 2 follow-up periods after hospitalization for collecting data about musculoskeletal post-COVID pain. Hospitalization and clinical data were collected from hospital medical records. From 2000 patients initially recruited, 1593 (44.6% women, age: 61 +/- 15 years) were assessed at T0 (hospital admission), T1 (mean: 8.0 +/- 1.5 months after discharge), and T2 (mean: 13.2 +/- 1.5 months after discharge). The prevalence of musculoskeletal pain (myalgia) was 30.3% (n = 483) at T0, increased to 43.4% (n = 692) at T1, and decreased to 37.8% (n = 603) at T2. The trajectory curve revealed a decreasing prevalence trend of musculoskeletal post-COVID pain the following years after hospitalization. According to the presence of pre-existing pain symptoms, the prevalence of new-onset post-COVID pain was 75.9%. Female sex (odds ratio [OR] 1.593, 95% confidence interval [CI] 1.148-2.211), history of musculoskeletal pain (OR 1.591, 95% CI 1.211-2.07), the presence of myalgia (OR 1.371, 95% CI 1.032-1.821) or headache (OR 2.278, 95% CI 1.622-3.199) at hospitalization, the days of hospitalization (OR 1.013, 95% CI 1.000-1.025), and the presence of post-COVID pain at T1 (OR 11.02, 95% CI 8.493-14.305) were factors associated with musculoskeletal post-COVID pain 1 year after hospitalization. In conclusion, musculoskeletal post-COVID pain remains highly prevalent 1 year after hospitalization. Female sex, previous history of pain symptoms, pain symptoms at onset, and days at hospital were factors associated with musculoskeletal post-COVID pain 1 year after hospitalization.
Learn More >Itching can decrease quality of life and exacerbate skin symptoms due to scratching. Itching not only contributes to disease progression but also triggers complications such as skin infections and eye symptoms. Therefore, controlling itching is very important in therapeutic management. In addition to the well-known histamine, IL-31, IL-4 and IL-13 have recently been reported as factors that induce itching. Itching may also be caused by factors other than these histamines. However, we do not know the extent to which these factors are involved in each disease. In addition, the degree of involvement is likely to vary among individuals. To date, antihistamines have been widely used to treat itching and are often effective, suggesting that histamine is more or less involved in itchy diseases. This review discusses the ligand-receptor perspective and describes the dynamics of G protein-coupled receptors, their role as biased agonists, their role as inverse agonists, proactive antihistamine therapy, and drug selection with consideration of impaired performance and anti-PAF effects.
Learn More >Following tissue injury, latent sensitization (LS) of nociceptive signaling can persist indefinitely, kept in remission by compensatory µ-opioid receptor constitutive activity (MOR) in the dorsal horn of the spinal cord. To demonstrate LS, we conducted plantar incision in mice and then waited 3-4 weeks for hypersensitivity to resolve. At this time (remission), systemic administration of the opioid receptor antagonist/inverse agonist naltrexone reinstated mechanical and heat hypersensitivity. We first tested the hypothesis that LS extends to serotonergic neurons in the rostral ventral medulla (RVM) that convey pronociceptive input to the spinal cord. We report that in male and female mice, hypersensitivity was accompanied by increased Fos expression in serotonergic neurons of the RVM, abolished upon chemogenetic inhibition of RVM 5-HT neurons, and blocked by intrathecal injection of the 5-HTR antagonist ondansetron; the 5-HTR antagonist MDL-11,939 had no effect. Second, to test for MOR, we microinjected the MOR inverse agonist CTAP and/or neutral opioid receptor antagonist 6β-naltrexol. Intra-RVM CTAP produced mechanical hypersensitivity at both hindpaws. 6β-naltrexol had no effect by itself, but blocked CTAP-induced hypersensitivity. This indicates that MOR, rather than an opioid ligand-dependent mechanism, maintains LS in remission. We conclude that incision establishes LS in descending RVM 5-HT neurons that drives pronociceptive 5-HTR signaling in the dorsal horn, and this LS is tonically opposed by MOR in the RVM. The 5-HT receptor is a promising therapeutic target for the development of drugs to prevent the transition from acute to chronic post-surgical pain.Surgery leads to latent pain sensitization and a compensatory state of endogenous pain control that is maintained long after tissue healing. Here we show that either chemogenetic inhibition of serotonergic neuron activity in the rostral ventromedial medulla (RVM), or pharmacological inhibition of 5-HT receptor signaling at the spinal cord blocks behavioral signs of post-surgical latent sensitization. We conclude that µ-opioid receptor constitutive activity (MOR) in the RVM opposes descending serotonergic facilitation of LS, and that the 5-HT receptor is a promising therapeutic target for the development of drugs to prevent the transition from acute to chronic post-surgical pain.
Learn More >An increasing number of studies have suggested that the important role of vasoactive peptides, such as pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and calcitonin gene-related peptide (CGRP), in the pathophysiology of migraine seems undeniable in adults, but studies in pediatric migraine patients remain scarce. We prospectively investigated CGRP and PACAP-38 plasma levels in children with migraine during ictal and interictal periods and compared the results between migraine patients with aura and without aura. We were the first to explore the diagnostic value of a combination of CGRP and PACAP-38.
Learn More >OnabotulinumtoxinA has been widely used for control of chronic migraine. The aim of the current study was to evaluate the efficacy of different doses of the onabotulinumtoxinA therapy in patients with chronic migraine.
Learn More >Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all <0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (<0.05). Gray matter volumes in the left insula were associated with pain symptoms (r=0.26, -0.29; <0.05). No significant associations were observed for either PA or sedentary time (>0.05). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.
Learn More >The human gut microbiome can be altered with probiotics, prebiotics, synbiotics, and anti-inflammatory foods and spices as part of an evidence-based strategy that targets inflammation and pain in common orthopedic conditions. Implementing these strategies avoids adverse effects associated with nonsteroidal anti-inflammatory drugs and minimizes the potential for opioid use. This review focuses exclusively on human trials studying the effects of gut microbiome alterations to address pain and inflammatory markers in common orthopedic conditions: osteoarthritis, rheumatoid arthritis, fractures/osteoporosis, and bone pain associated with chemotherapy. Individualized supplementation strategies can be further explored with the information in this review. [. 20XX;XX(X):xx-xx.].
Learn More >Harris (1999) proposed that pain can arise in the absence of tissue damage because changes in the cortical representation of the painful body part lead to incongruences between motor intention and sensory feedback. This idea, subsequently termed the sensorimotor theory of pain, has formed the basis for novel treatments for pathological pain. Here we review the evidence that people with pathological pain have changes to processes contributing to sensorimotor function: motor function, sensory feedback, cognitive representations of the body and its surrounding space, multisensory processing, and sensorimotor integration. Changes to sensorimotor processing are most evident in the form of motor deficits, sensory changes, and body representations distortions, and for Complex Regional Pain Syndrome (CRPS), fibromyalgia, and low back pain. Many sensorimotor changes are related to cortical processing, pain, and other clinical characteristics. However, there is very limited evidence that changes in sensorimotor processing actually lead to pain. We therefore propose that the theory is more appropriate for understanding why pain persists rather than how it arises.
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