Pain
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Randomized Controlled Trial
Effects of hypnosis, cognitive therapy, hypnotic cognitive therapy, and pain education in adults with chronic pain: a randomized clinical trial.
Chronic pain is a significant health problem worldwide with limited pharmacological treatment options. This study evaluated the relative efficacy of 4 treatment sessions each of 4 nonpharmacological treatments: (1) hypnotic cognitive therapy (using hypnosis to alter the meaning of pain); (2) standard cognitive therapy; (3) hypnosis focused on pain reduction, and (4) pain education. One hundred seventy-three individuals with chronic pain were randomly assigned to receive 4 sessions of 1 of the 4 treatments. ⋯ Pretreatment to posttreatment improvements were observed across the 4 treatment conditions on the secondary outcomes of pain interference and depressive symptoms, with some return towards pretreatment levels at 12-month follow-up. No significant between-group differences emerged in omnibus analyses, and few statistically significant between-group differences emerged in the planned pairwise analyses, although the 2 significant effects that did emerge favored hypnotic cognitive therapy. Future research is needed to determine whether the significant differences that emerged are reliable.
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The opioid epidemic has plagued the United States with high levels of abuse and poor quality of life for chronic pain patients requiring continuous use of opioids. New drug discovery efforts have been implemented to mitigate this epidemic; however, new medications are still limited by low efficacy and/or high side effect and abuse potential. Intermittent fasting (IF) has recently been shown to improve a variety of pathological states, including stroke and neuroinflammation. ⋯ Seeking a mechanism for these improvements, we found that the mu-opioid receptor showed enhanced efficacy and reduced tolerance in the spinal cord and periaqueductal gray, respectively, from IF mice using a S-GTPγS coupling assay. These improvements in receptor function were not due to changes in mu-opioid receptor protein expression. These data suggest that a daily IF diet may improve the therapeutic index of acute and chronic opioid therapies for pain patients in the clinic, providing a novel tool to improve patient therapy and reduce potential abuse.
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Chronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive, and emotional information and in conditioned pain modulation. We previously reported widespread epigenetic reprogramming in the PFC many months after nerve injury in rodents. ⋯ Hundreds of differentially methylated genes were identified, including many with known function in pain. Pathway analysis revealed enrichment in genes related to stimulus response at early time points, immune function at later time points, and actin and cytoskeletal regulation throughout the time course. These results emphasize the importance of considering pain chronicity in both pain research and in treatment optimization.
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Classical Ehlers-Danlos syndrome (cEDS) is a connective tissue disorder caused by heterozygous mutations in one of the type V collagen-encoding genes, COL5A1 or COL5A2. cEDS is characterized by generalized joint hypermobility and instability, hyperextensible, fragile skin, and delayed wound healing. Chronic pain is a major problem in cEDS patients, but the underlying mechanisms are largely unknown, and studies in animal models are lacking. Therefore, we assessed pain-related behaviors in haploinsufficient Col5a1 mice, which clinically mimic human cEDS. ⋯ We observed a significant decrease in intraepidermal nerve fiber density, with fewer nerves crossing the epidermis, and a decreased total nerve length of Col5a1 mice compared to WT. In summary, male and female Col5a1 mice show hypersensitivity to mechanical stimuli, indicative of generalized sensitization of the nervous system, in conjunction with an aberrant organization of cutaneous nociceptors. Therefore, Col5a1 mice will provide a useful tool to study mechanisms of pain associated with cEDS.