Pain
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Spinal nociception can be facilitated by 5-HT2 receptors in neuropathic pain. We investigated the involvement of glutamate receptors in dorsal neuron hyperexcitation that is promoted by 5-HT2B receptor (5-HT2BR) after spinal nerve ligation (SNL) in the rat. Augmentation of C-fiber-evoked potentials by spinal superfusion with 5-HT2BR agonist BW 723C86 in nerve-ligated rats was impeded by co-administration of NMDA receptor (NMDAR) antagonist D-AP5, but not by mGluR1/5 antagonist AIDA or mGluR2/3 antagonist LY 341495. ⋯ Chronic blockade of 5-HT2BR with selective antagonist SB 204741 after SNL bilaterally decreased the following: (i) PKCγ up-regulation in synaptic fraction, (ii) phosphorylation of NMDAR subunit NR1 (serine 889) in synaptic fraction, and (iii) co-localization of both PKCγ and phosphorylated NR1 with postsynaptic marker PSD-95. Chronic delivery of SB 204741 bilaterally attenuated thermal and mechanical allodynia occurring after SNL, particularly at day 2 post injury. These findings suggest that transient activation of the PKCγ/NMDAR pathway is critically involved in 5-HT2BR-mediated facilitation in the SNL model of neuropathic pain.
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Chronic widespread pain (CWP) is a complex condition characterized by central hyperexcitability and altered descending control of nociception. However, nociceptive input from deep tissues is suggested to be an important drive. N-Acylethanolamines (NAEs) are endogenous lipid mediators involved in regulation of inflammation and pain. ⋯ This is the first study demonstrating that CNSP and CWP differ in levels of NAEs in response to a low-force exercise which induces pain. Increases in pain intensity as a consequence of low-force exercise were associated with low levels of PEA and SEA in CNSP and CWP. These results indicate that PEA and SEA have antinociceptive roles in humans.
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This study aimed to investigate the modulating effects of emotional context on pain perception in 16 patients with fibromyalgia syndrome (FMS) and 16 healthy control (HC) subjects. An infrared laser was used to apply individually adapted painful stimuli to the dorsum of the left hand. The emotional background of the painful stimuli was modulated by concurrent presentations of negative, neutral, and positive picture stimuli selected from the International Affective Picture System. ⋯ In contrast, FMS patients showed a quadratic trend for pain intensity ratings indicating a lack of pain reduction by the positive pictures. In addition, the FMS patients showed less activation in secondary somatosensory cortex, insula, orbitofrontal cortex, and anterior cingulate cortex during the positive picture pain trials. Our results suggest that fibromyalgia patients are less efficient in modulating pain by positive affect and may benefit less from appetitive events than healthy control subjects.
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The lack of efficacy of rehabilitative approaches to the management of chronic whiplash-associated disorders (WAD) may be in part due to heterogeneity of the clinical presentation of this patient population. The aim of this study was to identify homogeneous subgroups of patients with chronic WAD on the basis of symptoms of PTSD and sensory hypersensitivity and to compare the clinical presentation of these subgroups. Successive k-means cluster analyses using 2, 3 and 4 cluster solutions were performed by using data for 331 (221 female) patients with chronic (>3 months) WAD. ⋯ The nPnH cluster was the largest cluster, comprising 43.5% of the sample. The PH cluster had significantly worse disability, pain intensity, self-reported mental health status and cervical range of motion in comparison to the nPnH and nPH clusters. These data provide further evidence of the heterogeneity of the chronic WAD population and the association of a more complex clinical presentation with higher disability and pain in this patient group.
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To explore whether chronic pain is associated with cardiovascular risk factors and identify whether increased distribution or intensity of pain is associated with cardiovascular risk, participants in Generation Scotland: The Scottish Family Health study completed pain questionnaires recording the following: presence of chronic pain, distribution of pain, and intensity of chronic pain. Blood pressure, lipids, blood glucose, smoking history, waist-hip ratio, and body mass index were recorded; Framingham 10-year coronary heart disease (CHD) risk scores were calculated and a diagnosis of metabolic syndrome derived. Associations between chronic pain and cardiovascular risk were explored. ⋯ However, cardiovascular disease risk factors contributing to metabolic syndrome were more prevalent in those reporting high-intensity chronic pain. This large population-based study has demonstrated that chronic pain, and in particular high-intensity chronic pain, is associated with an increased prevalence of cardiovascular risk factors and metabolic syndrome. The 10-year CHD risk score and metabolic syndrome correlate well with increased pain intensity, but not with widespread pain.