The journal of pain : official journal of the American Pain Society
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Emotional regulation is an important variable in the experience of pain. Currently, there are no experimental investigations of the relation between emotional regulation and pain. The goal of the present study work was to analyze differences in pain perception and mood generated by the cold-pressor (CPT) experimental paradigm in women with high and low emotional regulation. Two groups of women were formed as a function of their level of emotional regulation: women with high emotional repair (N = 24) and women with low emotional repair (N = 28), all of whom performed the CPT. The results show that the women with a high score in emotional repair reported having experienced less sensory pain and affective pain during the immersion, as well as a more positive affective state before beginning the task. During the experimental task, they also reported a better mood, thus displaying lower impact of the experience of pain. ⋯ Emotional regulation is proposed as a key element to manage the emotional reaction that accompanies the experience of acute pain experimentally induced by the CPT experimental paradigm in a sample of healthy women.
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Clinical and preclinical data concur that sleep disruption causes hyperalgesia, but the brain mechanisms through which sleep and pain interact remain poorly understood. Evidence that pontine components of the ascending reticular activating system modulate sleep and nociception encouraged the present study testing the hypothesis that hypocretin-1 (orexin-A) and an adenosine receptor agonist administered into the pontine reticular nucleus, oral part (PnO) each alter thermal nociception. Adult male rats (n = 23) were implanted with microinjection guide tubes aimed for the PnO. The PnO was microinjected with saline (control), hypocretin-1, the adenosine A(1) receptor agonist N(6)-p-sulfophenyladenosine (SPA), the hypocretin receptor-1 antagonist N-(2-Methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl-urea (SB-334867), and hypocretin-1 plus SB-334867. As an index of antinociceptive behavior, the latency (in seconds) to paw withdrawal away from a thermal stimulus was measured following each microinjection. Compared to control, antinociception was significantly increased by hypocretin-1 and by SPA. SB-334867 increased nociceptive responsiveness, and administration of hypocretin-1 plus SB-334867 blocked the antinociception caused by hypocretin-1. These results suggest for the first time that hypocretin receptors in rat PnO modulate nociception. ⋯ Widely distributed and overlapping neural networks regulate states of sleep and pain. Specifying the brain regions and neurotransmitters through which pain and sleep interact is an essential step for developing adjunctive therapies that diminish pain without disrupting states of sleep and wakefulness.
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Randomized Controlled Trial
A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers.
Desensitization of nociceptive sensory nerve endings is the basis for the therapeutic use of capsaicin in neuropathic pain syndromes. This study evaluated the pharmacodynamic effects of a single 60-minute application of NGX-4010, a high-concentration (8% w/w) capsaicin patch, on both thighs of healthy volunteers. Epidermal nerve fiber (ENF) density and quantitative sensory testing (QST) using thermal, tactile, and sharp mechanical-pain (pinprick) stimuli were evaluated 1, 12 and 24 weeks after capsaicin exposure. After 1 week, there was about an 80% reduction of ENF density compared to unexposed sites. In addition, there was about an 8% increase in tactile thresholds compared to baseline and the proportion of stimuli reported as sharp mechanical pain decreased by about 15 percentage points. Twelve weeks after exposure to capsaicin, ENF regeneration was evident, but not complete, and sharp mechanical-pain sensation and tactile thresholds did not differ from unexposed sites. Nearly full (93%) ENF recovery was observed at 24 weeks. No statistically significant changes in heat- or cold-detection thresholds were observed at any time point. NGX-4010 was generally well tolerated. Transient, mild warming or burning sensations at the site of application were common adverse effects. ⋯ This article evaluates the effect of a single 60-minute NGX-4010 application on ENF density and QST in healthy volunteers followed for 24 weeks. The results help predict the long-term safety of NGX-4010 applications in patients.
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This study compared recalled average pain, assessed at the end of the day, with the average of real-time pain ratings recorded throughout the day among patients with osteoarthritis (OA). Participants (N = 157) with hand, hip, or knee OA completed electronic pain diaries on 1 weekend day and 1 weekday. Diaries included at least 7 pain ratings per day, immediately after waking and every 2 hours following, using a visual analog scale (VAS) scored as 1 to 100 (scores not seen by participants). At the end of each diary day, participants rated their average pain that day on the same VAS. Pearson correlations examined associations between recalled average pain and the average of real-time pain ratings that day. Mixed models, including interaction terms, examined whether associations between recalled and actual average pain ratings differed according to the following patient characteristics: joint site, age, race, gender, study enrollment site, and pain catastrophizing. Correlations between recalled and actual average pain ratings were r = .88 for weekdays and r = .86 for weekends (P < .0001). In mixed models, there were no significant interaction terms for any patient characteristics. In summary, patients with OA accurately recalled their average pain over a 1-day period, and this did not differ according to any patient characteristics examined. ⋯ This study showed that patients with OA accurately recalled their average pain over a single-day period, and this did not differ according to patient characteristics. Results of this study indicate that end-of-day recall is a practical and valid method for assessing patients' average pain during a day.
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Peripheral nerve injury leads to neuropathic pain, but the underlying mechanisms are not clear. The TRPV1 channel expressed by nociceptors is one receptor for noxious heat and inflammatory molecules. Lumbar 4 (L4) spinal nerve ligation (SNL) in mice induced persistent heat hyperalgesia 4 to 10 days after injury. The heat hypersensitivity was completely reversed by the TRPV1 antagonist A-425619. Furthermore, DRG neurons were isolated from the injured L4 ganglia or adjacent L3 ganglia 4 to 10 days after L4 SNL. Whole-cell patch-clamp recordings were performed and heat stimuli (22 degrees C to 50 degrees C/3 s) were applied to the soma. Neurons were classified by soma size and isolectin-B4 (IB4) binding. Among directly injured L4 neurons, SNL increased the percentage of small-diameter IB4-positive neurons that were heat-sensitive from 13% (naive controls) to 56% and conversely decreased the proportion of small IB4-negative neurons that were heat-sensitive from 66% (naive controls) to 34%. There was no change in IB4 binding in neurons from the injured ganglia. Surprisingly, in neurons from the adjacent L3 ganglia, SNL had no effect on the heat responsiveness of either IB4-positive or negative small neurons. Also, SNL had no effect on heat responses in medium-large-diameter neurons from either the injured or adjacent ganglia. ⋯ TRPV1 function is upregulated in IB4-positive sensory neurons, and TRPV1 is responsible for the behavioral heat hypersensitivity in the spinal nerve ligation model. Because IB4-positive neurons may contribute to the emotional perception of pain, TRPV1 antagonists, targeting both sensory and affective pain components, could have broad analgesic effects.