Pain
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Randomized Controlled Trial
Pain response to cannabidiol in induced acute nociceptive pain, allodynia, and hyperalgesia by using a model mimicking acute pain in healthy adults in a randomized trial (CANAB I).
Preclinical studies have demonstrated the analgesic potential of cannabidiol (CBD). Those suggesting an effect on pain-processing receptors have brought CBD back into focus. This study assessed the effect of CBD on acute pain, hyperalgesia, and allodynia compared with placebo. ⋯ Pain ratings (mean ± SD) did not differ significantly after CBD application compared with placebo (5.2 ± 0.7 vs 5.3 ± 0.7, P-value 0.928), neither did the areas of hyperalgesia and allodynia differ significantly after CBD application compared with placebo (hyperalgesia 23.9 ± 19.2 cm2 vs 27.4 ± 17.0 cm2, P-value 0.597; allodynia 16.6 ± 13.1 cm2 vs 17.3 ± 14.1 cm2, P-value 0.884). The CBD whole blood level (median, first to third quartile) was 2.0 µg/L (1.5-5.1) 60 minutes and 5.0 µg/L (4.0-10.4) 130 minutes after CBD application. Although the oral application of 800-mg CBD failed to show a significant effect, it is important to focus future research on different dosing, routes of administration, and CBD as a part of multimodal treatment strategies before negating its effects on acute pain.
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Randomized Controlled Trial
Efficacy and safety of single-dose DFN-15 for treatment of acute postsurgical dental pain: a randomized, double-blind, placebo-controlled study.
The analgesic efficacy and safety of DFN-15, a new oral liquid formulation of celecoxib with more rapid absorption than the capsule, were evaluated in the treatment of acute pain in adult patients after dental surgery. In this randomized, double-blind, placebo-controlled, dose-ranging study, 120 otherwise healthy adults who underwent the extraction of bilateral impacted mandibular third molar teeth and experienced moderate to severe pain postsurgery were randomly assigned, in a 1:1:1:1 ratio, to receive one dose of either placebo or DFN-15 at 3 doses: 62.5, 125, and 250 mg. Participants were evaluated at prespecified time points over 8 hours after study drug administration, using several instruments, including the 11-point Numerical Pain Rating Scale, 5-point Pain Relief Scale, and 5-point Treatment Satisfaction Scale. ⋯ All 3 doses of DFN-15 were significantly superior to placebo in SPID6 (least square mean difference over placebo: -756.6, -1120.7, and -1355.1, P < 0.0001 for all comparisons). In addition, DFN-15 was generally superior to placebo in other endpoints, including reduction of pain intensity, speed and magnitude of pain relief, treatment satisfaction, and rescue medication use. DFN-15 was similar to placebo in the incidence of adverse events with no apparent dose-related effects.
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Clinically significant new or worsening pain (CSNWP) is a common, yet often overlooked, sequelae of sexual assault. Little is known regarding factors influencing the development of CSNWP in sexual assault survivors. The current study used data from a recently completed prospective study to evaluate whether posttraumatic alterations in arousal and reactivity in the early aftermath of sexual assault influence the transition from acute to clinically significant new or worsening persistent pain. ⋯ A structural equation model adjusted for age, race, past trauma exposure, and preassault pain levels suggested that posttraumatic alterations in arousal/reactivity symptoms 1 week after assault partially mediated the transition from acute to persistent CSNWP. A significant portion (41%) of women sexual assault survivors develop CSNWP 6 weeks postassault. Posttraumatic arousal/reactivity symptoms in the early aftermath of assault contribute to CSNWP development; such symptoms are potential targets for secondary preventive interventions to reduce chronic postassault pain.
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Exercise and pain neuroscience education (PNE) have both been used as standalone treatments for chronic musculoskeletal pain. The evidence supporting PNE as an adjunct to exercise therapy is growing but remains unclear. The aim of this systematic review and meta-analysis was to evaluate the effect of combining PNE and exercise for patients with chronic musculoskeletal pain, when compared with exercise alone. ⋯ Long-term outcomes (>12 weeks) were only available for 2 studies and therefore were not suitable for meta-analysis. Meta-analysis revealed a significant difference in pain (weighted mean differences, -2.09/10; 95% confidence interval [CI], -3.38 to -0.80; low certainty), disability (standardized mean difference, -0.68; 95% CI, -1.17 to -0.20; low certainty), kinesiophobia (standardized mean difference, -1.20; CI, -1.84 to -0.57; moderate certainty), and pain catastrophizing (weighted mean differences, -7.72; 95% CI, -12.26 to -3.18; very low certainty) that favoured the combination of PNE and exercise. These findings suggest that combining PNE and exercise in the management of chronic musculoskeletal pain results in greater short-term improvements in pain, disability, kinesiophobia, and pain catastrophizing relative to exercise alone.
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The effects of expectations on pain perception are often studied using large differences in pain probabilities between experimental conditions, although they may be far more subtle in clinical contexts and, therefore, more difficult to detect. The current study aimed to investigate at which point subtle differences in pain probabilities can be detected and lead to differentiable expectations and perceptions. Furthermore, we investigated whether instructions can aid learning from experience and enhance subsequent pain modulatory effects. ⋯ As revealed by drift diffusion modeling, learning from experience was insufficient for the development of a bias towards low pain even when it was highly likely. By contrast, when explicit information was provided, perception became more nuanced with the direction and extent of bias, capturing the subtle differences in pain probabilities. These findings highlight that the use of instructions to foster the detection of subtle pain improvements during pain treatment to enhance their cognitive pain modulatory effects warrant further investigation.