Pain
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Patients with chronic pain often have accompanying cognitive deficiency, which may reduce their quality of life and hamper efficient medical treatment. Alteration of extracellular glycine concentration may affect cognitive function and spinal pain signaling. In the present study, we assessed recognition memory by novel-object recognition and found that mice developing mechanical hypersensitivity after peripheral nerve injury exhibited impaired recognition ability for novelty, which was never observed in mice provided the selective glycine transporter 1 (GlyT1) inhibitor N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS) systemically. ⋯ These findings imply that chronic pain has a crucial influence on hippocampal plasticity related to cognitive function, and strongly suggest that increasing the extracellular level of glycine via blockade of GlyT1 is a potential therapeutic approach for chronic pain with memory impairment. Chronic pain crucially influences hippocampal plasticity related to cognitive function. Increasing the extracellular level of glycine via blockade of GlyT1 is a potential therapeutic approach for chronic pain with memory impairment.
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Pain catastrophizing is associated with enhanced temporal summation of pain (TS-Pain). However, because prior studies have found that pain catastrophizing is not associated with a measure of spinal nociception (nociceptive flexion reflex [NFR] threshold), this association may not result from changes in spinal nociceptive processes. The goal of the present study in healthy participants was to examine the relationship between trait (traditional) and state (situation-specific) pain catastrophizing and temporal summation of NFR (TS-NFR) and TS-Pain. ⋯ Trait catastrophizing was not related to TS-Pain or TS-NFR. Together, these results confirm prior studies that indicate that catastrophizing enhances pain via supraspinal processes rather than spinal processes. Moreover, because catastrophizing was associated with TS-Pain but not TS-NFR, caution is warranted when using pain ratings to infer temporal summation of spinal nociceptive processes.
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Regional decreases in grey matter volume as detected by magnetic resonance imaging-based volumetry have been reported in several clinical chronic pain cohorts. Here, we used voxel-based morphometry in a nonclinical cohort to investigate whether grey matter alterations also occur in older individuals (aged 40-85 years) from the general population. Based on self-report of pain, we identified 31 pain-free controls, 45 subjects with ongoing pain (low back pain, headache, or lower extremity joint pain) who had at least moderate pain on more than 3 days/month, and 29 individuals with past pain (stopped for >12 months). ⋯ No grey matter volume decreases were found in the group with pain that had stopped for >12 months. These results show that pain-related grey matter volume decreases are present in individuals from the general population. The lack of morphometric anomalies in subjects with past pain supports recent evidence suggesting that pain-related grey matter changes are reversible after cessation of pain.
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Patients with Parkinson's disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. ⋯ The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P<.02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities.
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Peripheral inflammation alters AMPA receptor (AMPAR) subunit trafficking and increases AMPAR Ca(2+) permeability at synapses of spinal dorsal horn neurons. However, it is unclear whether AMPAR trafficking at extrasynaptic sites of these neurons also changes under persistent inflammatory pain conditions. Using patch-clamp recording combined with Ca(2+) imaging and cobalt staining, we found that, under normal conditions, an extrasynaptic pool of AMPARs in rat substantia gelatinosa (SG) neurons of spinal dorsal horn predominantly consists of GluR2-containing Ca(2+)-impermeable receptors. ⋯ This increase was also accompanied by an inward rectification of AMPA-induced currents and enhancement of sensitivity to a highly selective Ca(2+)-permeable AMPAR blocker, IEM-1460. Electron microcopy and biochemical assays additionally showed an increase in the amount of GluR1 at extrasynaptic membranes in dorsal horn neurons 24h post-CFA. Taken together, our findings indicate that CFA-induced inflammation increases functional expression and proportion of extrasynaptic GluR1-containing Ca(2+)-permeable AMPARs in tonically firing excitatory dorsal horn neurons, suggesting that the altered extrasynaptic AMPAR trafficking might participate in the maintenance of persistent inflammatory pain.