The journal of pain : official journal of the American Pain Society
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GABAA receptors in the central nucleus of amygdala are involved in pain- and itch-related responses.
Itch and pain are unpleasant sensations that distress many patients with disease. However, most studies have focused on the neural mechanisms of pain, and much less effort has been devoted to itch. It has been reported that itch and pain might share a common pathway, and γ-aminobutyric acid type A (GABA(A)) receptors in the central nucleus of the amygdala (CeA) are involved in pain modulation. However, the contribution of GABAA receptors in the CeA to the modulation of itch remains poorly understood. Herein, we report that bilateral intra-CeA microinjection of a selective GABAA receptor agonist muscimol hydrochloride (Mus; 50 ng per side), but not a selective GABAA receptor antagonist bicuculline (Bic; 20 ng per side) or vehicle, showed significant analgesic effects, reflected by an increase in tail-flick latency and a decrease in allyl isothiocyanate (mustard oil)-evoked ipsilateral forelimb wipes. More importantly, rats subjected to intra-CeA infusion of Bic showed a significantly greater number of scratching bouts and time in acute and chronic pruritus animal models than control rats. Conversely, intra-CeA infusion of Mus in animal models dramatically decreased the number of scratching bouts and time compared with control rats. In addition, intra-CeA infusion of Bic or Mus at the current dose had no obvious effects on other behaviors including locomotor activity and spontaneous facial grooming in rats subjected to cheek microinjection of 5-hydroxytryptamine. Taken together, these results indicate that the GABA(A) receptor-mediated inhibitory system in the CeA is involved in itch modulation as well as is known in pain control. ⋯ Itch, especially chronic itch, remains a challenge in clinic. Results of this study showed that the GABAA receptors in the CeA play an important role in itch modulation, which might help us to better understand the mechanisms of itch and subsequently develop novel mechanisms-based strategies to treat chronic itch in clinic.
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Comparative Study
Reorganized Trunk Muscle Activity During Multi-Directional Floor Perturbations After Experimental Low Back Pain: A Comparison Of Bilateral Versus Unilateral Pain.
Low back pain changes trunk muscle activity after external perturbations but the relationship between pain intensities and distributions and their effect on trunk muscle activity remains unclear. The effects of unilateral and bilateral experimental low back pain on trunk muscle activity were compared during unpredictable multidirectional surface perturbations in 19 healthy participants. Pain intensity and distribution were assessed using a visual analogue scale (VAS) and pain drawings. Root mean square (RMS) of the electromyographic (EMG) signals from 6 trunk muscles bilaterally after each perturbation was extracted and averaged across perturbations. The difference (ΔRMS-EMG) and absolute difference (absolute ΔRMS-EMG) RMS from baseline conditions were extracted for each muscle during pain conditions and averaged bilaterally for back and abdominal muscle groups. Bilateral compared with unilateral pain induced higher VAS scores (P < .005) and larger pain areas (P < .001). Significant correlation was present between VAS scores and muscle activity during unilateral (P < .001) and bilateral pain (P < .001). Compared with control injections ΔRMS-EMG increased in the back (P < .03) and abdominal (P < .05) muscles during bilateral and decreased in the back (P < .01) and abdominal (P < .01) muscles during unilateral pain. Bilateral pain caused greater absolute ΔRMS-EMG changes in the back (P < .01) and abdominal (P < .01) muscle groups than unilateral pain. ⋯ This study provided novel observations of differential trunk muscle activity in response to perturbations dependent on pain intensity and/or pain distribution. Because of complex and variable changes the relevance of clinical examination of muscle activity during postural tasks is challenged.
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The Brief Pain Inventory (BPI) has been psychometrically evaluated worldwide in adult patients with cancer-related and chronic pain in several languages, but never in nursing home residents with chronic pain. To address this gap, we evaluated the validity of a modified version of the BPI, the BPI for nursing home residents (BPI-NHR) in individuals who resided in German nursing homes. One analytic sample included 137 nursing home residents (mean age, 83.3 years; SD, 8.0 years) without any missing values. An extended sample also included individuals with previous missing values that were substituted with the personal mean (n = 163; mean age, 83.3 years; SD, 8.3 years). Principal axis factoring with oblimin rotation was used to compute the final 2-factor solution for the substituted sample. These factors explained 71.7% of the variance. Internal consistency was calculated using Cronbach α, and showed excellent results. Concurrent validity was tested using nonparametric correlation analyses of the BPI-NHR with the pain medication scale. The present findings support the reliability and validity of the BPI-NHR for very old nursing home residents. Further evaluation of this measure is needed to examine face validity and the effect of multimorbidity on pain interference with function. ⋯ In this article we present psychometric properties of the BPI originally developed to assess cancer pain, extended to measure chronic nonmalignant pain in younger and middle-aged patients, and now further developed to measure pain intensity and interference with function among very old nursing home residents. Thus, the BPI-NHR might assist clinicians and researchers interested in assessment of pain intensity and interference in elderly individuals who reside in nursing homes.
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Depression, pain catastrophizing, and anxiety commonly co-occur with chronic pain. However, the degree to which improvement in these psychological comorbidities predicts subsequent pain outcomes and, in particular, the relative effects of these 3 psychological factors with respect to each other is only partially known. Longitudinal analysis of 250 primary care patients with chronic musculoskeletal pain enrolled in the Stepped Care to Optimize Pain care Effectiveness (SCOPE) trial was examined, using data gathered at baseline, and at 3 and 12 months. Mixed effects model repeated measures analyses were used to determine if changes in depression, pain catastrophizing, and anxiety predicted a subsequent reduction in pain intensity or interference and pain-related disability. Defining a clinically significant change as twice the standard error of measurement for each predictor, we found that a 2-standard error of measurement improvement in depression, pain catastrophizing, and anxiety resulted in, respectively, an effect size decrease in pain intensity or interference of .45, .33, and .12; a 14%, 12%, and 6% reduction in the number of pain-specific disability days; and a 43%, 30%, and 28% decreased likelihood of high disability (defined as ≥10 pain-specific disability days in the past 4 weeks). In summary, improvements in 3 common psychological comorbidities predicted better pain outcomes. ⋯ Because depression, pain catastrophizing, and anxiety commonly accompany chronic pain and might adversely affect pain outcomes, treatment of these modifiable psychological factors is warranted to optimize the effectiveness of pain-specific therapies.
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Expectation and previous experience are both well established key mediators of placebo and nocebo effects. However, the investigation of their respective contribution to placebo and nocebo responses is rather difficult because most placebo and nocebo manipulations are contaminated by pre-existing treatment expectancies resulting from a learning history of previous medical interventions. To circumvent any resemblance to classical treatments, a purely psychological placebo-nocebo manipulation was established, namely, the "visual stripe pattern-induced modulation of pain." To this end, experience and expectation regarding the effects of different visual cues (stripe patterns) on pain were varied across 3 different groups, with either only placebo instruction (expectation), placebo conditioning (experience), or both (expectation + experience) applied. Only the combined manipulation (expectation + experience) revealed significant behavioral and physiological placebo-nocebo effects on pain. Two subsequent experiments, which, in addition to placebo and nocebo cues, included a neutral control condition further showed that especially nocebo responses were more easily induced by this psychological placebo and nocebo manipulation. The results emphasize the great effect of psychological processes on placebo and nocebo effects. Particularly, nocebo effects should be addressed more thoroughly and carefully considered in clinical practice to prevent the accidental induction of side effects. ⋯ Even purely psychological interventions that lack any resemblance to classical pain treatments might alter subjective and physiological pain correlates. A manipulation of treatment expectation and actual treatment experience were mandatory to elicit this effect. Nocebo effects were especially induced, which indicated the necessity for prevention of accidental side effects besides exploitation of placebo responses.