Pain
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Randomized Controlled Trial
A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain.
Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans. ⋯ Liposomal CBD (20 mg/day) was as effective as the highest dose of nonliposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the 4-week analysis period. This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans are warranted.
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Randomized Controlled Trial
Attention to breath sensations does not engage endogenous opioids to reduce pain.
The endogenous opioidergic system is critically involved in the cognitive modulation of pain. Slow-breathing-based techniques are widely used nonpharmacological approaches to reduce pain. Yet, the active mechanisms of actions supporting these practices are poorly characterized. ⋯ Self-reported "focusing on the breath" was identified as the operational feature particularly unique to the mindfulness-meditation and slow paced-breathing, but not sham-mindfulness meditation. Across all individuals, attending to the breath was associated with naloxone insensitive pain-relief. These findings provide evidence that slow breathing combined with attention to breath reduces pain independent of endogenous opioids.
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Randomized Controlled Trial Multicenter Study
Efficacy and safety of propranolol for treatment of temporomandibular disorder pain: a randomized, placebo-controlled clinical trial.
Propranolol is a nonselective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18 to 65 years with temporomandibular disorder myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. ⋯ Propranolol was likewise efficacious for a ≥50% reduction in FPI (number-needed-to-treat = 6.1, P = 0.03). Adverse event rates were similar between treatment groups, except for more frequent fatigue, dizziness, and sleep disorder in the propranolol group. Propranolol was not different from placebo in reducing mean FPI but was efficacious in achieving ≥30% and ≥50% FPI reductions after 9 weeks of treatment among temporomandibular disorder participants.
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Randomized Controlled Trial
Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes.
We aimed to evaluate the efficacy of an enhanced mindfulness-based stress reduction (MBSR+) vs stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n = 50) with SMH (n = 48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then biweekly for another 8 weeks. ⋯ Reduction in headache-related disability was greater for MBSR+ (59.6 [95% CI, 57.9-61.3] to 54.6 [95% CI, 52.9-56.4]) than SMH (59.6 [95% CI, 57.7-61.5] to 57.5 [95% CI, 55.5-59.4]) (P = 0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. Enhanced mindfulness-based stress reduction is an effective treatment option for episodic migraine.
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Randomized Controlled Trial
Learning mechanisms in nocebo hyperalgesia: the role of conditioning and extinction processes.
Nocebo hyperalgesia is a clinically relevant phenomenon and may be formed as a result of associative learning, implemented by classical conditioning. This study explored for the first time distinct nocebo conditioning methods and their consequences for nocebo attenuation methods. Healthy participants (N = 140) were recruited and randomized to the following nocebo hyperalgesia induction groups: conditioning with continuous reinforcement (CRF), conditioning with partial reinforcement (PRF), and a sham-conditioning control group. ⋯ However, compared with CRF, conditioning with PRF resulted in more resistance to counterconditioning. These findings demonstrate that the more ambiguous learning method of PRF can induce nocebo hyperalgesia and may potentially explain the treatment resistance and chronification seen in clinical practice. Further research is required to establish whether attenuation with counterconditioning is generalizable to clinical settings.