Autonomic Recalibration: A Promising Approach for Alleviating Myofascial Pain Explored in a Retrospective Case Series.

This retrospective case series introduces autonomic recalibration (AR) as a novel approach for alleviating chronic myofascial pain. The manuscript explores the rationale, theory, and practice of AR, which targets the autonomic nervous system (ANS) to restore homeostasis and reduce pain. The involvement of the ANS in pain modulation and the role of autonomic imbalance in chronic pain are discussed, emphasizing the potential benefits of addressing autonomic dysregulation through AR. The technique combines manual interventions and patient education, relying on neuroplastic adaptations. Three diverse case reports are presented to illustrate the effectiveness of AR in patients with different sources of pain. Each case presents a unique clinical scenario, including a nine-year-old male diagnosed with spondylolisthesis, a 68-year-old male with a history of abdominal surgeries, and a 56-year-old male with chronic low back pain following lumbar fusion surgery. In all cases, AR resulted in pain relief, improved sleep, and restoration of functional abilities. These findings support the potential of AR as an effective alternative approach for myofascial pain. Further research is warranted to validate these outcomes and investigate the underlying mechanisms of AR.

Mechanisms of cannabinoid tolerance.

Cannabis has been used recreationally and medically for centuries, yet research into understanding the mechanisms of its therapeutic effects has only recently garnered more attention. There is evidence to support the use of cannabinoids for the treatment of chronic pain, muscle spasticity, nausea and vomiting due to chemotherapy, improving weight gain in HIV-related cachexia, emesis, sleep disorders, managing symptoms in Tourette syndrome, and patient-reported muscle spasticity from multiple sclerosis. However, tolerance and the risk for cannabis use disorder are two significant disadvantages for cannabinoid-based therapies in humans. Recent work has revealed prominent sex differences in the acute response and tolerance to cannabinoids in both humans and animal models. This review will discuss evidence demonstrating cannabinoid tolerance in rodents, non-human primates, and humans and our current understanding of the neuroadaptations occurring at the cannabinoid type 1 receptor (CB1R) that are responsible tolerance. CB1R expression is downregulated in tolerant animals and humans while there is strong evidence of CB1R desensitization in cannabinoid tolerant rodent models. Throughout the review, critical knowledge gaps are indicated and discussed, such as the lack of a neuroimaging probe to assess CB1R desensitization in humans. The review discusses the intracellular signaling pathways that are responsible for mediating CB1R desensitization and downregulation including the action of G protein-coupled receptor kinases, ß-arrestin2 recruitment, c-Jun N-terminal kinases, protein kinase A, and the intracellular trafficking of CB1R. Finally, the review discusses approaches to reduce cannabinoid tolerance in humans based on our current understanding of the neuroadaptations and mechanisms responsible for this process.

Differential Response in Ethanol Behaviors of Female Rats Given Various Weight Loss Surgeries.

AIMS: Currently, the only effective treatment for morbid obesity and its comorbidities is weight loss surgery (WLS). Growing evidence suggests that different types of WLS, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), have differential effects on alcohol consumption in humans and rats. Thus, we aimed to directly compare the effects of these two surgical procedures, for the first time in female rats, and to determine whether presence or absence of the ghrelin-producing stomach tissue has critical influence on postoperative alcohol intake. METHODS: We performed two experiments using an identical behavioral protocol, a continuous-access two-bottle choice protocol for various concentrations of ethanol (EtOH). In Experiment 1, 23 high fat diet (HFD) obese, female rats were randomized to three groups: RYGB, SG or sham-operated food-restricted (Sham) controls. In Experiment 2, HFD obese female rats received either sham (n = 11) or a modified RYGB surgery where the remnant stomach was removed (RYGB-X; n = 12). RESULTS: SG rats drank significantly less than RYGB for 4, 6 and 8% and significantly less than Sham for 6, 8 and 8% reinstatement. RYGB-X consumed significantly less EtOH than Sham across all concentrations, reaching significance for 6 and 8% reinstatement. CONCLUSION: These findings confirm reduced EtOH consumption by female SG rats as opposed to increased intake following RYGB, and provide the first experimental evidence that the remnant stomach in the RYGB procedure is contributory. Future studies in rats and humans are warranted to confirm that ghrelin plays a critical role in susceptibility to AUD development following WLS.