Pain
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Randomized Controlled Trial Multicenter Study Comparative Study
Efficacy and safety of the α4β2 neuronal nicotinic receptor agonist ABT-894 in patients with diabetic peripheral neuropathic pain.
Preclinical and clinical studies suggest that neuronal nicotinic receptor (NNR) agonists may be a novel and effective therapy for numerous painful conditions. Analgesic efficacy and safety of the highly selective α(4)β(2) NNR agonist ABT-894 was evaluated in 2 separate randomized, double-blind, multicenter, placebo-controlled clinical trials in patients with diabetic peripheral neuropathic pain (DPNP). Study 1 (280 patients randomized) tested 1, 2, and 4 mg ABT-894 twice daily compared with placebo and 60 mg duloxetine once per day over 8 weeks of treatment. ⋯ All dose levels of ABT-894 were well tolerated, and no significant safety issues were identified. These results are in contrast to the outcome of a previously reported study of DPNP using the less selective α(4)β(2) NNR agonist ABT-594, which demonstrated efficacy compared with placebo, albeit with significant tolerability limitations. The failure of the highly selective α(4)β(2) NNR agonist ABT-894 indicates that it may not be possible to define a therapeutic index for this mechanism or that selectively targeting α(4)β(2) NNRs may not be a viable approach to treating neuropathic pain.
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Randomized Controlled Trial Comparative Study
Acute experimental endotoxemia induces visceral hypersensitivity and altered pain evaluation in healthy humans.
Growing evidence suggests that systemic immune activation plays a role in the pathophysiology of pain in functional bowel disorders. By implementing a randomized crossover study with an injection of endotoxin or saline, we aimed to test the hypothesis that endotoxin-induced systemic inflammation increases visceral pain sensitivity in humans. Eleven healthy men (mean ± standard error of the mean age 26.6 ± 1.1 years) received an intravenous injection of either lipopolysaccharide (LPS; 0.4 ng/kg) or saline on 2 otherwise identical study days. ⋯ Pain thresholds correlated with interleukin 6 at +1h (r=0.60, P<.05) and +3h (r=0.67, P<.05) within the LPS condition. This report is novel in that it demonstrates that a transient systemic immune activation results in decreased visceral sensory and pain thresholds and altered subjective pain ratings. Our results support the relevance of inflammatory processes in the pathophysiology of visceral hyperalgesia and underscore the need for studies to further elucidate immune-to-brain communication pathways in gastrointestinal disorders.
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Randomized Controlled Trial Comparative Study
Patients who display protective pain behaviors are viewed as less likable, less dependable, and less likely to return to work.
In the present study, participants (ie, observers) watched video sequences of patients with chronic back pain performing a physically demanding lifting task. Participants were asked to make judgments about patients' levels of pain and readiness to work. For each patient, observers were also asked to make judgments about personality traits relevant to work performance and employment. ⋯ Analyses also revealed that patients displaying protective pain behaviors were perceived as being significantly less likable, less dependable, and less ready to work than patients displaying other forms of pain behavior. Discussion addresses the processes by which pain behaviors might influence observers' judgments about patients' personality traits and readiness to work. Implications of the present findings for clinical practice and the management of patients presenting with pain conditions are also discussed.
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Randomized Controlled Trial Comparative Study
Effects of strength vs aerobic exercise on pain severity in adults with fibromyalgia: a randomized equivalence trial.
Strength training and aerobic exercise have beneficial effects on pain in adults with fibromyalgia. However, the equivalence of strengthening and aerobic exercise has not been reported. The primary aim of this randomized equivalence trial involving patients with fibromyalgia admitted to an interdisciplinary pain treatment program was to test the hypothesis that strengthening (n=36) and aerobic (n=36) exercise have equivalent effects (95% confidence interval within an equivalence margin ± 8) on pain, as measured by the pain severity subscale of the Multidimensional Pain Inventory. ⋯ Significant improvements in pain severity (P<.001), peak Vo(2) (P<.001), strength (P<.001), and pain thresholds (P<.001) were observed from baseline to week 3 in the intent-to-treat analysis; however, patients in the aerobic group (mean change 2.0 ± 2.6 mL/kg/min) experienced greater gains (P<.013) in peak Vo(2) compared to the strength group (mean change 0.4 ± 2.6 mL/kg/min). Knowledge of the equivalence and physiological effects of exercise have important clinical implications that could allow practitioners to target exercise recommendations on the basis of comorbid medical conditions or patient preference for a particular type of exercise. This study found that strength and aerobic exercise had equivalent effects on reducing pain severity among patients with fibromyalgia.
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Randomized Controlled Trial Comparative Study
Comparison of glutamate-evoked pain between the temporalis and masseter muscles in men and women.
Pain in myofascial temporomandibular disorder (TMD) can affect both the masseter and temporalis muscles. Glutamate injection into the masseter muscle evokes pain that is greater in men than in women and this pain is attenuated by co-injection of the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine (10 mmol/L) in men. Animal studies suggested that pain induced by peripheral NMDA receptor activation could differ between the temporalis and masseter muscles and between men and women. ⋯ Women reported significantly greater glutamate-evoked masseter muscle pain than men (P<.03). Co-injection of ketamine, at higher dose than previously used, was equally effective in attenuating glutamate-evoked pain from both muscles in both genders (P<.01). The current findings indicate that the characteristics of pain generated by intramuscular injection of glutamate vary for different masticatory muscles and may be partially generated through activation of peripheral NMDA receptors.