Pain
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Psychedelic serotonergic agonists such as psilocybin have recently been shown to produce sustained benefit in refractory depression, end of life anxiety, and addiction when administered in hallucinogenic doses and coupled with psychotherapy. Although it has been suggested that similar high-dose protocols may help chronic pain conditions, there are few published clinical trials of psychedelics for pain. The use of these agents in subpsychedelic doses for chronic pain management has received even less attention. ⋯ Furthermore, the efficacy of pain relief and, in some cases, the duration of the effect were magnified when coupled with functional exercise. In addition, in 1 case, repeated dosing seemed to produce increased relief, suggesting a possible long-term plasticity-mediated effect. These commonalities highlight psilocybin's therapeutic potential in the treatment of chronic pain that warrants further investigation.
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People with chronic pain often fear and avoid movements and activities that were never paired with pain. Safe movements may be avoided if they share some semantic relationship with an actual pain-associated movement. This study investigated whether pain-associated operant responses (movements) can become categorically associated with perceptually dissimilar responses, thus motivating avoidance of new classes of safe movements-a phenomenon known as category-based avoidance generalization. ⋯ This suggests that operant pain-related avoidance can generalize to safe behaviors, which are not perceptually, but categorically, similar to a pain-associated behavior. This form of pain-related avoidance generalization is problematic because category-based relations can be extremely wide reaching and idiosyncratic. Thus, category-based generalization of operant pain-related avoidance merits further investigation.
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Painful diabetic peripheral neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects; some are ineffective, and treatment with opioids is associated with use dependence and addiction. ⋯ Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin-induced diabetic rats and mini pigs without any adverse effects as compared with capsaicin at therapeutic doses, which induces intense pain during application. Resiniferatoxin cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated calcitonin gene-related peptide release in the skin samples of diabetic rats and mini pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.
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This study investigated the tolerability and preliminary efficacy of duloxetine as an alternative nonopioid therapeutic option for the prevention of persistent musculoskeletal pain (MSP) among adults presenting to the emergency department with acute MSP after trauma or injury. In this randomized, double-blind, placebo-controlled study, eligible participants (n = 78) were randomized to 2 weeks of a daily dose of one of the following: placebo (n = 27), 30 mg duloxetine (n = 24), or 60 mg duloxetine (n = 27). Tolerability, the primary outcome, was measured by dropout rate and adverse effects. ⋯ In both types of analyses, the size of the effect of duloxetine was larger in MVC vs non-MVC injury. Consistent with the role of stress systems in the development of chronic pain after traumatic stress, our data indicate duloxetine may be a treatment option for reducing the transition from acute to persistent MSP. Larger randomized controlled trials are needed to confirm these promising results.
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Randomized Controlled Trial
A double-blind phase II randomized controlled trial of an online cognitive bias modification for interpretation program with and without psychoeducation for people with chronic pain.
Cognitive bias modification for interpretation (CBM-I) is an effective intervention for anxiety, but there is only a single trial in people with chronic pain. The aim of this randomized controlled trial was to test CBM-I with and without psychoeducation for people with chronic pain. We randomized 288 participants to 4 groups comprising treatment (CBM-I vs placebo) with or without psychoeducation. ⋯ Cognitive bias modification of interpretation reduced stress but only for those who also received psychoeducation. This trial shows that CBM-I has promise in the management of pain, but there was limited evidence that psychoeducation improved the efficacy of CBM-I. Cognitive bias modification of interpretation was administered entirely remotely and is highly scalable, but future research should focus on paradigms that lead to better engagement of people with chronic pain with CBM-I.