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The aim of the present study was to explore the pain modulation effects of motor imagery (MI) and action observation (AO) of specific neck therapeutic exercises both locally, in the cervical region, and remotely. A single-blind, placebo clinical trial was designed. A total of 30 patients with chronic neck pain (CNP) were randomly assigned to an AO group, MI group, or placebo observation (PO) group. Pain pressure thresholds (PPTs) of C2/C3, trapezius muscles, and epicondyle were the main outcome variables. Secondary outcomes included heart rate measurement. Statistically significant differences were observed in PPTs of the cervical region in the AO and MI groups between the preintervention and first postintervention assessment. Significant differences were found in the AO group in the epicondyle between the preintervention, first and second post-intervention assessments. Regarding heart rate response, differences were found in the AO and MI groups between the preintervention and average intervention measurements. AO and MI induce immediate pain modulation in the cervical region and AO also induces remote hypoalgesia. OA appears to lead to greater pain modulation as well as a greater heart rate response, however, both should be clinically considered in patients with CNP.
Learn More >The dorsal root ganglia (DRG) contain the somas of first-order sensory neurons critical for somatosensation. Due to technical difficulties, DRG neuronal activity in awake behaving animals remains unknown. Here, we develop a method for imaging DRG at cellular and subcellular resolution over weeks in awake mice. The method involves the installation of an intervertebral fusion mount to reduce spinal movement, and the implantation of a vertebral glass window without interfering animals' motor and sensory functions. In vivo two-photon calcium imaging shows that DRG neuronal activity is higher in awake than anesthetized animals. Immediately after plantar formalin injection, DRG neuronal activity increases substantially and this activity upsurge correlates with animals' phasic pain behavior. Repeated imaging of DRG over 5 weeks after formalin injection reveals persistent neuronal hyperactivity associated with ongoing pain. The method described here provides an important means for in vivo studies of DRG functions in sensory perception and disorders.
Learn More >Mouse models of rare monogenic forms of migraine provide a unique experimental system to study the cellular and circuit mechanisms of the primary brain dysfunctions causing a migraine disorder. Here, we discuss the migraine-relevant phenotypes and the migraine-relevant functional alterations in the brain of five genetic mouse models of migraine, four of which carry mutations derived from patients with familial hemiplegic migraine (FHM) and the fifth carry a mutation from patients with both phenotypically normal MA and familial advanced sleep phase syndrome (FASPS). We focus on the latter mouse model, in which a ubiquitous serine-threonine kinase is mutated, and on two mouse models of pure FHM, in which a voltage-gated calcium channel controlling neurotransmitter release at most brain synapses and a Na/K ATPase that is expressed mainly in astrocytes in the adult brain are mutated, respectively. First, we describe the behavioral phenotypes of the genetic animal models and review the evidence that an increased susceptibility to experimentally induced cortical spreading depression (CSD) is a key migraine-relevant phenotype common to the five models. Second, we review the synaptic alterations in the cerebral cortex of the genetic models of migraine and discuss the mechanisms underlying their increased susceptibility to CSD. Third, we review the alterations in the trigeminovascular pain pathway and discuss possible implications for migraine pain mechanisms. Finally, we discuss the insights into migraine pathophysiology obtained from the genetic models of migraine, in particular regarding the mechanisms that make the brain of migraineurs susceptible to the ignition of "spontaneous" CSDs. Although the reviewed functional studies support the view of migraine as a disorder of the brain characterized by dysfunctional regulation of the excitatory/inhibitory balance in specific neuronal circuits, much work remains to be done in the genetic mouse models e.g. to identfy the relevant dysfunctional circuits and to establish whether and how the alterations in the function of specific circuits (in the cerebral cortex and/or other brain areas) are state-dependent and may, in certain conditions, favor CSD ignition and the migraine attack.
Learn More >Receptor-type ion channels are critical for detection of noxious stimuli in primary sensory neurons. Transient receptor potential (TRP) channels mediate pain sensations and promote a variety of neuronal signals that elicit secondary neural functions (such as calcitonin gene-related peptide [CGRP] secretion), which are important for physiological functions throughout the body. In this review, we focus on the involvement of TRP channels in sensing acute pain, inflammatory pain, headache, migraine, pain due to fungal infections, and osteo-inflammation. Furthermore, action potentials mediated via interactions between TRP channels and the chloride channel, anoctamin 1 (ANO1), can also generate strong pain sensations in primary sensory neurons. Thus, we also discuss mechanisms that enhance neuronal excitation and are dependent on ANO1, and consider modulation of pain sensation from the perspective of both cation and anion dynamics.
Learn More >Exergames are non-immersive versions of virtual reality that involve physical exercise and have shown several benefits on physical fitness and quality of life in women with fibromyalgia. However, the effects on brain dynamics are still unknown.
Learn More >Genome-wide-association studies in chronic low back pain patients identified sepiapterin reductase as a high interest target for developing new analgesics. Here we used F NMR fragment screening for the discovery of novel, ligand-efficient SPR inhibitors. We report the crystal structures of six chemically diverse inhibitors complexed with SPR, identifying relevant interactions and binding modes in the sepiapterin pocket. Exploration of our initial fragment screening hit led to double-digit nanomolar inhibitors of SPR with excellent ligand efficiency.
Learn More >Opioids are the primary choice for managing chronic cancer pain. However, many nonopioid therapies are currently prescribed for chronic cancer pain with little published evidence comparing their efficacy.
Learn More >Psychological approaches to the management of chronic pain have proven to be very effective in allowing patients to better manage their symptoms and with overall functioning.
Learn More >We aimed to compare serum biomarkers of inflammation, redox status and cartilage degradation between chronic low back pain (cLBP) patients with and without Modic 1 changes. We used a convenience sample of patients recruited from a single center, case-control study, conducted in a tertiary care center. From December, 2014 to May, 2016, 2,292 patients were consecutively screened, 34 met inclusion criteria and were prospectively enrolled in the present study. Cases (n = 13) were defined as patients with Modic 1 changes detected on MRI and controls (n = 21) as cLBP patients without (Modic 0). To assess serum biomarkers of inflammation, redox status and cartilage degradation, fasting serum samples were collected in a standardized manner and analyzed by immunoassays and spectrophotometry. Mean (95% CI) age was 44.1 (40.0-48.1) years and mean LBP duration was 72.5 (53.0-91.9) months. Serum biomarkers of inflammation (IL-1β, IL-6, IL-8 and TNF-α), redox status (total thiols, advanced oxidation protein products and carbonyl groups) and cartilage degradation (Coll2-1 and Coll2-1NO) did not differ between cLBP patients with and without Modic 1 changes. In summary, we did not find any differences in serum biomarkers between cLBP patients with and without Modic 1 changes. Interpretation is limited by convenience sampling and small sample size.
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