Pain
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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.
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TRPA1 is an ion channel of the TRP family that is expressed in some sensory neurons. TRPA1 activity provokes sensory symptoms of peripheral neuropathy, such as pain and paraesthesia. We have used a grease gap method to record axonal membrane potential and evoked compound action potentials (ECAPs) in vitro from human sural nerves and studied the effects of mustard oil (MO), a selective activator of TRPA1. ⋯ Capsaicin caused a profound reduction in C fibre conduction in both species but had no effect on the amplitude of the A component. Lidocaine (30 mM) depolarized rat saphenous nerves acutely, and when rat nerves were pretreated with 30 mM lidocaine to mimic the exposure of human nerves to local anaesthetic during surgery, the effects of MO were abolished whilst the effects of capsaicin were unchanged. This study demonstrates that the local anaesthetic lidocaine desensitizes TRPA1 ion channels and indicates that it may have additional mechanisms for treating neuropathic pain that endure beyond simple sodium channel blockade.
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It has been estimated that up to 54% of the variance in postoperative pain experience may be predicted with preoperative pain responses to experimental stimuli, with suprathreshold heat pain as the most consistent test modality. This study aimed to explore whether 2 heat test paradigms could predict postoperative pain after total knee arthroplasty (TKA). Patients scheduled for elective, unilateral, primary TKA under spinal anesthesia were consecutively included in this prospective, observational study. ⋯ A weak correlation [rho (95% confidence interval); P value] was observed between pain from POD 1 to 7 and pain response to short [rho=0.25(0.04 to 0.44); P=.02] and to long [rho=0.27 (0.07 to 0.46); P=.01] heat pain stimulation. However, these positive correlations were not supported by the linear and logistic regression analyses, in which only anxiety, preoperative pain, and pain catastrophizing were significant explanatory variables (but with low R-squares; 0.05 to 0.08). Pain responses to 2 types of preoperative heat stimuli were not independent clinically relevant predictors for postoperative pain after TKA.
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Randomized Controlled Trial
Specifying the nonspecific components of acupuncture analgesia.
It is well known that acupuncture has pain-relieving effects, but the contribution of specific and especially nonspecific factors to acupuncture analgesia is less clear. One hundred one patients who developed pain of ≥ 3 on a visual analog scale (VAS, 0 to 10) after third molar surgery were randomized to receive active acupuncture, placebo acupuncture, or no treatment for 30 min with acupuncture needles with potential for double-blinding. Patients' perception of the treatment (active or placebo) and expected pain levels (VAS) were assessed before and halfway through the treatment. ⋯ Expected pain levels accounted for significant and progressively larger amounts of the variance in pain ratings after both active and placebo acupuncture (up to 69.8%). This is the first study to show that under optimized blinding conditions, nonspecific factors such as patients' perception of and expectations toward treatment are central to the efficacy of acupuncture analgesia and that these factors may contribute to self-reinforcing effects in acupuncture treatment. To obtain an effect of acupuncture in clinical practice, it may therefore be important to incorporate and optimize these factors.
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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.