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The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the molecular expression profiles of mRNAs in neurons, glia and infiltrating immune cells. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Previously, we have shown that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg/kg) reduces inflammation of the sciatic nerve and relieves pain-like behavior for up to 6 days. Here, we use this targeted therapy to explore the impact on mRNA expression changes in both pain and pain-relieved states. Sciatic nerve tissue recovered from CCI animals is used to evaluate the mRNA expression profiles utilizing quantitative PCR. We observe mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine expression. Furthermore, genes associated with adhesion of macrophages, as well as changes in the neuronal and glial mRNAs are observed. Moreover, genes associated with neuropathic pain including Maob, Grin2b/NMDAR2b, TrpV3, IL-6, Cacna1b/Ca2.2, Itgam/Cd11b, Scn9a/Na1.7, and Tac1 were all found to respond to the celecoxib loaded nanoemulsion during pain relief as compared to those animals that received drug-free vehicle. These results demonstrate that by targeting macrophage production of PGE at the site of injury, pain relief includes partial reversal of the gene expression profiles associated with chronic pain.
Learn More >Observing pain in others can enhance our own pain. Two aspects of this effect remain unknown or controversial: first, whether it depends on the 'painfulness' of the visual stimulus; second, whether it reflects a genuine bias in perception or rather a bias in the memory encoding of the percept. Pain ratings and vegetative skin responses were recorded while 21 healthy volunteers received electric nociceptive shocks under three experimental conditions: (i) observing a painful contact between the body and a harmful object; (ii) observing a non-painful body contact, (iii) observing a control scene where the body and the object are not in contact. Pain reports and vegetative responses were enhanced exclusively when the subjects observed a painful body contact. The effect on perception was immediate, abated 3 sec after the shock, and positively correlated with the magnitude of vegetative arousal. This suggests that (a) hyperalgesia during observation of painful scenes was induced by their pain-related nature, and not by the simple body contact, and (b) hyperalgesia emerged from a very rapid bias in the perceptual encoding of the stimulus, and was not the result of a retrospective bias in memory recollection. Observing pain-depicting scenes can modify the processing of concomitant somatic stimuli, increasing their arousal value and shifting perception toward more painful levels.
Learn More >The World Health Organization Disability Assessment Schedule (WHODAS) 2.0 is a generic instrument to assess disability. Pain and psychological factors seem to play a pronounced disabling role in fibromyalgia (FM). There are few studies that investigate the factors associated with disability in patients with fibromyalgia from the patient's perspective. Information about FM disability using self-reported questionnaires is limited. This study aimed to assess the relationship between the ordinal response variable (degree of disability), and four explanatory variables: pain intensity, depression, anxiety, and alexithymia.
Learn More >Pharmacology and optogenetics are widely used in neuroscience research to study the central and peripheral nervous systems. While both approaches allow for sophisticated studies of neural circuitry, continued advances are, in part, hampered by technology limitations associated with requirements for physical tethers that connect external equipment to rigid probes inserted into delicate regions of the brain. The results can lead to tissue damage and alterations in behavioral tasks and natural movements, with additional difficulties in use for studies that involve social interactions and/or motions in complex 3-dimensional environments. These disadvantages are particularly pronounced in research that demands combined optogenetic and pharmacological functions in a single experiment. Here, we present a lightweight, wireless, battery-free injectable microsystem that combines soft microfluidic and microscale inorganic light-emitting diode probes for programmable pharmacology and optogenetics, designed to offer the features of drug refillability and adjustable flow rates, together with programmable control over the temporal profiles. The technology has potential for large-scale manufacturing and broad distribution to the neuroscience community, with capabilities in targeting specific neuronal populations in freely moving animals. In addition, the same platform can easily be adapted for a wide range of other types of passive or active electronic functions, including electrical stimulation.
Learn More >The current study aimed to validate the parent-proxy IMPACT-III (IMPACT-III-P) in a sample of youth diagnosed with inflammatory bowel disease (IBD). Parent-proxy report measures are standard for pediatric psychosocial assessment, and the IMPACT-III-P will provide a more comprehensive representation of HRQOL. Reliability and validity analyses were conducted.
Learn More >Tibial fracture is associated with inflammatory reaction leading to severe pain syndrome. Bradykinin receptor activation is involved in inflammatory reactions, but has never been investigated in fracture pain.
Learn More >The Fc gamma receptor I (FcγRI; CD64) is the high-affinity receptor of the immunoglobulin G protein (IgG). It is usually expressed in immune cells and has recently been identified to distribute in the nervous system and play critical roles in various neurological disorders. Presently, the impacts of FcγRI in neuropathic pain was largely unknown. Here, we aimed to investigate the impacts of FcγRI in neuropathic pain through pain-related neurobehavioral studies and underlying mechanisms by biochemical methods in animal and cell models. Specifically, we first utilized the chronic constriction injury (CCI) rat model that displayed neuropathic pain related symptoms and signs, including thermal hyperalgesia and mechanical allodynia. These neurobehavioral defects were significantly attenuated by the anti-FcγRI antibody, which was associated with reduced levels of neuropeptide substance P, C, and TNF-α. Furthermore, we validated our animal findings using the embryonically neural crest-originated PC12 cell model. We found that stimulation of the IgG immune complex led to increased levels of FcγRI and inflammatory mediators, which were attenuated by the anti-FcγRI antibody in these cells. Collectively, our results from animal and cell-based studies suggest that FcγRI is a critical player for peripheral nerve injury-induced neuropathic pain by mediating pain-related immunological events, which therefore may provide a new therapeutic target for protection against chronic pain.
Learn More >The STarT Back Screening Tool (SBT) identifies patients with low back pain (LBP) at risk of a worse prognosis of persistent disabling back pain, and thereby facilitates triage to appropriate treatment level. However, the SBT does not consider the pain distribution, which is a known predictor of chronic widespread pain (CWP). The aim of this study was to determine if screening by the SBT and screening of multisite chronic widespread pain (MS-CWP) could identity individuals with a worse prognosis. A secondary aim was to analyze self-reported health in individuals with and without LBP, in relation to the combination of these two screening tools.
Learn More >Trunk muscle dysfunction is often regarded as a key feature of non-specific chronic low back pain (NSCLBP) despite being poorly understood and variable with increases, decreases and no change in muscle activity reported. Differences in thoraco-lumbar kinematics have been observed in motor control impairment NSCLBP subgroups (Flexion Pattern, Active Extension Pattern) during static postures and dynamic activities. However, potential differences in muscle activity during functional tasks has not been established in these subgroups to date.
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