The journal of pain : official journal of the American Pain Society
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We have recently shown that the prolongation of prostaglandin E2 hyperalgesia in a preclinical model of chronic pain-hyperalgesic priming-is mediated by release of cyclic adenosine monophosphate from isolectin B4-positive nociceptors and its metabolism by ectonucleotidases to produce adenosine. The adenosine, in turn, acts in an autocrine mechanism at an A1 adenosine receptor whose downstream signaling mechanisms in the nociceptor are altered to produce nociceptor sensitization. We previously showed that antisense against an extracellular matrix molecule, versican, which defines the population of nociceptors involved in hyperalgesic priming, eliminated the prolongation of prostaglandin E2 hyperalgesia. To further evaluate the mechanisms at the interface between the extracellular matrix and the nociceptor's plasma membrane involved in hyperalgesia prolongation, we interrupted a plasma membrane molecule involved in versican signaling, integrin β1, with an antisense oligodeoxynucleotide. Integrin β1 antisense eliminated mechanical hyperalgesia induced by an adenosine A1 receptor agonist, cyclopentyladenosine, in the primed rat. We also disrupted a molecular complex of signaling molecules that contains integrin β1, lipid rafts, with methyl-β-cyclodextrin, which attenuated the prolongation without affecting the acute phase of prostaglandin E2 hyperalgesia, while having no effect on cyclopentyladenosine hyperalgesia. Our findings help to define the plasma membrane mechanisms involved in a preclinical model of chronic pain. ⋯ The present study contributes to a further understanding of mechanisms involved in the organization of messengers at the plasma membrane that participate in the transition from acute to chronic pain.
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Randomized Controlled Trial Comparative Study
Effectiveness of jyoti meditation for patients with chronic neck pain and psychological distress--a randomized controlled clinical trial.
Chronic neck pain is a common medical complaint partly mediated by psychosocial distress and having a high socioeconomic impact. There is preliminary evidence that stress reduction by meditation might be beneficial in chronic pain syndromes. We aimed to evaluate the effectiveness of an 8-week meditation program (jyoti meditation) in patients with chronic neck pain by means of a randomized clinical trial. Eighty-nine patients (aged 49.7 ± 10.5 years, 73 female) with chronic neck pain who scored >40 mm on a 100-mm visual analog scale and had concomitant increased perceived stress were randomized to an 8-week meditation program (jyoti meditation) with weekly 90-minute classes (n = 45) or to a home-based exercise program (n = 44) with a wait list offer for meditation. Both groups were instructed to practice at home. Outcomes were assessed at baseline and after 8 weeks. Primary outcome measure was change of mean pain at rest (visual analog scale score) from baseline to week 8. Secondary outcomes included pain at motion, functional disability, pain-related bothersomeness, perceived stress, quality of life, and psychological outcomes. Patients had neck pain for a mean of 11 years. Eighteen patients in the meditation group and 16 patients in the exercise group were lost to follow-up. Meditation training significantly reduced pain when compared to the exercise group after 8 weeks (reduction of 45.5 ± 23.3 mm to 21.6 ± 17.2 mm in the meditation group, and 43.8 ± 22.0 mm to 37.7 ± 21.5 mm in the exercise group; mean difference: 13.2 mm [95% confidence interval: 2.1, 24.4; P = .02]). Pain-related bothersomeness decreased more in the meditation group (group difference 11.0 mm [95% confidence interval: 1.0, 21.0; P = .03]). No significant treatment effects were found for pain at motion, psychological scores, and quality of life, although the meditation group showed nonsignificant greater improvements compared to the exercise group. In conclusion, meditation may support chronic pain patients in pain reduction and pain coping. Further well-designed studies including more active control comparisons and longer-term follow-up are warranted. ⋯ This article presents the results of a randomized controlled trial on the clinical effects of an 8-week meditation program or self-care exercise in patients with chronic neck pain. Meditation reduced pain at rest but not disability and might be a useful treatment option for pain management of chronic neck pain.
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Spatial summation of pain is well accepted but surprisingly understudied. Area-based summation refers to the increase in pain evoked by increasing the area of stimulation. Distance-based summation refers to the increase in pain evoked by increasing the distance between multiple stimuli. Although transcutaneous electrical stimulation has several advantages over other experimental pain paradigms, whether or not this modality evokes spatial summation remains unknown. We aimed to answer this question in order to lay the foundation for critical studies of spatial summation. Twenty-five healthy participants received stimuli on their forearm, and the primary outcome, pain intensity, was compared across 5 spatial configurations-1 with a single stimulus and 4 paired configurations at 0-, 5-, 10-, and 20-cm separations. Importantly, the potential confounder of a proximal-distal gradient in nociceptive sensitivity was removed in this study. Pain intensity was higher in response to the paired stimuli than in response to the single stimulus (P < .001), and the paired stimuli separated by 5, 10 and 20 cm, evoked greater pain than stimuli at a separation of 0 cm (P < .001), thus confirming both area- and distance-based summation, respectively. We conclude that transcutaneous electrical stimulation is appropriate for future investigations of spatial summation. ⋯ Distance-based summation is likely implicated in some clinical pain. However, current understanding for spatial summation is limited. This study demonstrates that transcutaneous electrical stimulation is safe, feasible, and valid for future investigations of spatial summation and will allow critical questions to be answered.
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Peer-reviewed publications of randomized clinical trials (RCTs) are the primary means of disseminating research findings. "Spin" in RCT publications is misrepresentation of statistically nonsignificant research findings to suggest treatment benefit. Spin can influence the way readers interpret clinical trials and use the information to make decisions about treatments and medical policies. The objective of this study was to determine the frequency with which 4 types of spin were used in publications of analgesic RCTs with nonsignificant primary analyses in 6 major pain journals. In the 76 articles included in our sample, 28% of the abstracts and 29% of the main texts emphasized secondary analyses with P values <.05; 22% of abstracts and 29% of texts emphasized treatment benefit based on nonsignificant primary results; 14% of abstracts and 18% of texts emphasized within-group improvements over time, rather than primary between-group comparisons; and 13% of abstracts and 10% of texts interpreted a nonsignificant difference between groups in a superiority study as comparable effectiveness. When considering the article conclusion sections, 21% did not mention the nonsignificant primary result, 22% were presented with no uncertainty or qualification, 30% did not acknowledge that future research was required, and 8% recommended the intervention for clinical use. ⋯ This article identifies relatively frequent "spin" in analgesic RCTs. These findings highlight a need for authors, reviewers, and editors to be more cognizant of how analgesic RCT results are presented and attempt to minimize spin in future clinical trial publications.
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The widely used Adult Responses to Children's Symptoms measures parental responses to child symptom complaints among youth aged 7 to 18 years with recurrent/chronic pain. Given developmental differences between children and adolescents and the impact of developmental stage on parenting, the factorial validity of the parent-report version of the Adult Responses to Children's Symptoms with a pain-specific stem was examined separately in 743 parents of 281 children (7-11 years) and 462 adolescents (12-18 years) with chronic pain or pain-related chronic illness. Factor structures of the Adult Responses to Children's Symptoms beyond the original 3-factor model were also examined. Exploratory factor analysis with oblique rotation was conducted on a randomly chosen half of the sample of children and adolescents as well as the 2 groups combined to assess underlying factor structure. Confirmatory factor analysis was conducted on the other randomly chosen half of the sample to cross-validate factor structure revealed by exploratory factor analyses and compare it to other model variants. Poor loading and high cross-loading items were removed. A 4-factor model (Protect, Minimize, Monitor, and Distract) for children and the combined (child and adolescent) sample and a 5-factor model (Protect, Minimize, Monitor, Distract, and Solicitousness) for adolescents was superior to the 3-factor model proposed in previous literature. Future research should examine the validity of derived subscales and developmental differences in their relationships with parent and child functioning. ⋯ This article examined developmental differences in the structure of a widely used measure of caregiver responses to chronic pain or pain-related chronic illness in youth. Results suggest that revised structures that differ across developmental groups can be used with youth with a range of clinical pain-related conditions.