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Deep brain stimulation (DBS) of the subthalamic nucleus, pallidum, and thalamus is an established therapy for various movement disorders. Limbic targets have also been increasingly explored for their application to neuropsychiatric and cognitive disorders. The brainstem constitutes another DBS substrate, although the existing literature on the indications for and the effects of brainstem stimulation remains comparatively sparse. The objective of this review was to provide a comprehensive overview of the pertinent anatomy, indications, and reported stimulation-induced acute and long-term effects of existing white and grey matter brainstem DBS targets. We systematically searched the published literature, reviewing clinical trial articles pertaining to DBS brainstem targets. Overall, 164 studies describing brainstem DBS were identified. These studies encompassed 10 discrete structures: periaqueductal/periventricular grey (n = 63), pedunculopontine nucleus (n = 48), ventral tegmental area (n = 22), substantia nigra (n = 9), mesencephalic reticular formation (n = 7), medial forebrain bundle (n = 8), superior cerebellar peduncles (n = 3), red nucleus (n = 3), parabrachial complex (n = 2), and locus coeruleus (n = 1). Indications for brainstem DBS varied widely and included central neuropathic pain, axial symptoms of movement disorders, headache, depression, and vegetative state. The most promising results for brainstem DBS have come from targeting the pedunculopontine nucleus for relief of axial motor deficits, periaqueductal/periventricular grey for the management of central neuropathic pain, and ventral tegmental area for treatment of cluster headaches. Brainstem DBS has also acutely elicited numerous motor, limbic, and autonomic effects. Further work involving larger, controlled trials is necessary to better establish the therapeutic potential of DBS in this complex area.
Learn More >Even though current prescribing trends reveal that high-dose opioid prescribing and opioid prescribing in general has decreased, sustained efforts are needed to help providers adopt and maintain safe prescribing behaviors. The purpose of this four-year type 2 effectiveness-implementation hybrid stepped wedge cluster randomized trial is to: (1) compare the clinical and cost effectiveness of electronic medical record-based clinical decision support [EMR-CDS] versus additional integrated, collaborative behavioral health [EMR-CDS + BHI-CCM] for opioid management of patients with co-morbid chronic non-cancer pain with depression or anxiety; and (2) examine facilitators and barriers to implementing these interventions within 35 primary care clinics in a integrated delivery health system. The EMR-CDS alerts providers to employ opioid risk mitigation and safe prescribing practices at the point of care. The BHI-CCM consists of primary care embedded community health workers for case management; licensed clinical social workers for cognitive behavioral therapy, and a clinical pharmacist for medication management who provide care management via telemedicine (virtual video or audio only visits) under the guidance of a consulting psychiatrist. The primary outcome is reduction in the percentage of patients with average daily opioid dose ≥50 mg morphine equivalent. Secondary outcomes include changes in service utilization, patient reported outcomes and processes of care. The investigators anticipate that study results will elucidate the role of technology versus care team optimization in changing opioid prescribing behaviors. The investigators further anticipate that integrated mental/behavioral health care will increase value-based care and the efficiency with which guideline concordant care is delivered.
Learn More >This study aimed to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effects of cytotoxic T lymphocyte-associated antigen-4Ig (CTLA-4Ig) administration in ovariectomized (OVX) mice. Eight-week-old female ddY mice were assigned to three groups: sham-operated mice (SHAM) treated with vehicle, OVX mice treated with vehicle (OVX), and OVX mice treated with CTLA-4Ig (CTLA-4Ig). Vehicle or CTLA-4Ig was injected intraperitoneally, starting immediately after surgery. After 4 weeks of treatment, mechanical sensitivity was examined, and the bilateral hind limbs were removed and evaluated by micro-computed tomography, immunohistochemical analyses, and messenger RNA expression analysis. Ovariectomy induced bone loss and mechanical hyperalgesia in the hindlimbs. CTLA-4Ig treatment prevented bone loss in the hindlimbs compared to vehicle administration in the OVX group. Moreover, mechanical hyperalgesia was significantly decreased in the CTLA-4Ig treatment group in comparison to the OVX group. The expression levels of tumor necrosis factor-α (TNF-α) and sclerostin (SOST), as well as the number of osteoclasts, were increased, and the expression level of Wnt-10b was decreased in the OVX group compared with the SHAM group, whereas these parameters were improved in the CTLA-4Ig group compared with the OVX group. The novelty of this research is that CTLA-4Ig administration prevented bone loss and mechanical hyperalgesia induced by ovariectomy in the hindlimbs.
Learn More >Acupuncture is a complex multi-component treatment that has shown promise for the treatment of Fibromyalgia (FM), however, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. We sought to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved.
Learn More >The pervasive use of opioid compounds for pain relief is rooted in their utility as one of the most effective therapeutic strategies for providing analgesia. While the detrimental side effects of these compounds have significantly contributed to the current opioid epidemic, opioids still provide millions of patients with reprieve from the relentless and agonizing experience of pain. The human experience of pain has long recognized the perceived unpleasantness entangled with a unique sensation that is immediate and identifiable from the first-person subjective vantage point as "painful." From this phenomenological perspective, how is it that opioids interfere with pain perception? Evidence from human lesion, neuroimaging, and preclinical functional neuroanatomy approaches is sculpting the view that opioids predominately alleviate the affective or inferential appraisal of nociceptive neural information. Thus, opioids weaken pain-associated unpleasantness rather than modulate perceived sensory qualities. Here, we discuss the historical theories of pain to demonstrate how modern neuroscience is revisiting these ideas to deconstruct the brain mechanisms driving the emergence of aversive pain perceptions. We further detail how targeting opioidergic signaling within affective or emotional brain circuits remains a strong avenue for developing targeted pharmacological and gene-therapy analgesic treatments that might reduce the dependence on current clinical opioid options.
Learn More >To evaluate the efficacy, tolerability, and safety of eptinezumab 100 and 300 mg compared with placebo in patients with the dual diagnosis of chronic migraine (CM) and medication-overuse headache (MOH).
Learn More >Many health care systems are beginning to encourage patients to use complementary and integrative health (CIH) therapies for pain management. Many clinicians have anecdotally reported that patients combining self-care CIH therapies with practitioner-delivered therapies report larger health improvements than do patients using practitioner-delivered or self-care CIH therapies alone. However, we are unaware of any trials in this area.
Learn More >The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care.
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