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Imidazoline receptors historically referred to a family of nonadrenergic binding sites that recognize compounds with an imidazoline moiety, although this has proven to be an oversimplification. For example, none of the proposed endogenous ligands for imidazoline receptors contain an imidazoline moiety but they are diverse in their chemical structure. Three receptor subtypes (I, I, and I) have been proposed and the understanding of each has seen differing progress over the decades. I receptors partially mediate the central hypotensive effects of clonidine-like drugs. Moxonidine and rilmenidine have better therapeutic profiles (fewer side effects) than clonidine as antihypertensive drugs, thought to be due to their higher I/-adrenoceptor selectivity. Newer I receptor agonists such as LNP599 [3-chloro-2-methyl-phenyl)-(4-methyl-4,5-dihydro-3-pyrrol-2-yl)-amine hydrochloride] have little to no activity on -adrenoceptors and demonstrate promising therapeutic potential for hypertension and metabolic syndrome. I receptors associate with several distinct proteins, but the identities of these proteins remain elusive. I receptor agonists have demonstrated various centrally mediated effects including antinociception and neuroprotection. A new I receptor agonist, CR4056 [2-phenyl-6-(1-imidazol-1yl) quinazoline], demonstrated clear analgesic activity in a recently completed phase II clinical trial and holds great promise as a novel I receptor-based first-in-class nonopioid analgesic. The understanding of I receptors is relatively limited. Existing data suggest that I receptors may represent a binding site at the Kir6.2-subtype ATP-sensitive potassium channels in pancreatic -cells and may be involved in insulin secretion. Despite the elusive nature of their molecular identities, recent progress on drug discovery targeting imidazoline receptors (I and I) demonstrates the exciting potential of these compounds to elicit neuroprotection and to treat various disorders such as hypertension, metabolic syndrome, and chronic pain.
Learn More >Neuropathic pain is a debilitating condition caused by the abnormal processing of somatosensory input. Synaptic inhibition in the spinal dorsal horn plays a key role in that processing. Mechanical allodynia – the misperception of light touch as painful – occurs when inhibition is compromised. Disinhibition is due primarily to chloride dysregulation caused by hypofunction of the potassium-chloride co-transporter KCC2. Here we show, in rats, that excitatory neurons are disproportionately affected. This is not because chloride is differentially dysregulated in excitatory and inhibitory neurons, but, rather, because excitatory neurons rely more heavily on inhibition to counterbalance strong excitation. Receptive fields in both cell types have a center-surround organization but disinhibition unmasks more excitatory input to excitatory neurons. Differences in intrinsic excitability also affect how chloride dysregulation affects spiking. These results deepen understanding of how excitation and inhibition are normally balanced in the spinal dorsal horn, and how their imbalance disrupts somatosensory processing.
Learn More >In this study, we investigated whether illusionary body ownership over artificial hands and non-corporeal objects modulates pain perception. Previous research has yielded to mixed results, but has separated painful stimulation used to test pain perception from the stimulation that was used to induce the illusion. Here, we used a variant of the rubber hand illusion (RHI) paradigm and induced the illusion directly via a combination of visual and painful stimuli. We presented heat pain stimuli at the real hand and visual stimuli beneath a rubber hand (part1), or a glass ball (part2). Illusion ratings were higher and pain ratings were lower in the synchronous compared to the asynchronous condition in both parts of the experiment. This study demonstrated the successful induction of a body illusion using a new visual-thermal method with painful stimuli. We showed that the RHI and interestingly also the glass ball has an analgesic effect on the perception of the heat pain stimuli. Our data suggests that induced ownership over artificial limbs but also over non-corporeal objects can reduce the perceived pain perception. This might be mediated via a partial referral of the perceived location of pain or respectively a distribution of pain over two locations. Perspective: This article presents a new visual-thermal method with painful stimuli for the induction of the Rubber Hand Illusion. An illusionary body ownership over artificial hands and non-corporeal has an analgesic effects on the perception of pain. Similar approaches might be useful to alleviate chronic pain, but needs further testing.
Learn More >Opioids are prescribed more frequently than nonpharmacologic treatments for persistent musculoskeletal pain (MSP). We estimate the association between the supply of physical therapy (PT) and mental health (MH) providers and early nonpharmacologic service use with high-risk opioid prescriptions among Medicare beneficiaries with persistent MSP.
Learn More >Intra-epidermal nerve fibers (IENFs) are presumed to comprise mainly of itch-transmitting nerve fibers, and variations in their density have been studied in itch disorders; epidermal nerve fiber density is also a criterion in diagnosing small fiber neuropathy in clinical neurological practice. IENFs are typically identified with 2-dimensional (2D) histological slides, but 2D sections do not accurately represent nerves, which branch out in three-dimensions (3D).
Learn More >To investigate the effectiveness chronic pain self-management support with pain science education and exercise (COMMENCE) on improving function, pain interference, work status, pain intensity, fatigue, psychological factors associated with pain, health care visits, satisfaction, and perceived change compared to usual care.
Learn More >(i) To investigate the prevalence of poor sleep quality and (ii) to explore the associations between clinical, cognitive and emotional factors and quality of sleep in patients with chronic widespread pain (CWP) attending multidisciplinary treatment.
Learn More >Anti-inflammatory corticosteroids are a common treatment for different conditions involving chronic pain and inflammation. Clinically used steroids target the glucocorticoid receptor (GR) for its anti-inflammatory effects. We previously reported that GR in sensory neurons may play central roles in some pain models and that GR immunoreactivity signal in dorsal root ganglia (DRG) decreased after local inflammation of the DRG (a model of low back pain). In the current study, we aimed to determine if similar changes in GR signal also exist in a skin inflammation model, the complete Freund's adjuvant (CFA) model (a model of peripheral inflammatory pain), in which the terminals of the sensory neurons rather than the somata are inflamed.
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