YokoCo

Pharmaceutical opioid consumption has been increasing worldwide, but disparities in access to these medications exist. Few countries of the WHO Eastern Mediterranean Region have well defined pain management policies.

Multimorbidity among cluster headache (CH) patients is considered to be high, but large studies are lacking. The aims were to explore the occurrence of diagnosis-specific multimorbidity among CH patients and matched references and possible associations of this with their sickness absence and disability pension.

Significant recent progress in understanding rheumatoid arthritis (RA) pathogenesis has led to improved treatment and quality of life. The introduction of targeted-biologic and -synthetic disease modifying anti-rheumatic drugs (DMARDs) has also transformed clinical outcomes. Despite this, RA remains a life-long disease without a cure. Unmet needs include partial response and non-response to treatment in many patients, failure to achieve immune homeostasis or drug free remission, and inability to repair damaged tissues. RA is now recognized as the end of a multi-year prodromal phase in which systemic immune dysregulation, likely beginning in mucosal surfaces, is followed by a symptomatic clinical phase. Inflammation and immune reactivity are primarily localized to the synovium leading to pain and articular damage, but is also associated with a broader series of comorbidities. Here, we review recently described immunologic mechanisms that drive breach of tolerance, chronic synovitis, and remission.

Pain chronicity involves unpleasant experience in both somatosensory and affective aspects, accompanied with the prefrontal cortex (PFC) neuroplastic alterations. However, whether specific PFC neuronal ensembles underlie pain chronicity remains elusive. Here we identify a nociceptive neuronal ensemble in the dorsomedial prefrontal cortex (dmPFC), which shows prominent reactivity to nociceptive stimuli. We observed that this ensemble shows distinct molecular characteristics and is densely connected to pain-related regions including basolateral amygdala (BLA) and lateral parabrachial nuclei (LPB). Prolonged chemogenetic activation of this nociceptive neuronal ensemble, but not a randomly transfected subset of dmPFC neurons, induces chronic pain-like behaviors in normal mice. By contrast, silencing the nociceptive dmPFC neurons relieves both pain hypersensitivity and anxiety in mice with chronic inflammatory pain. These results suggest the presence of specific dmPFC neuronal ensembles in processing nociceptive information and regulating pain chronicity.

Infrapatellar fat pad (IFP)/ synovial fibrosis is closely associated with the clinical symptoms of joint pain and stiffness, which contribute to locomotor restriction in osteoarthritis (OA) patients. Hence, this study was designed to gain insight on whether losartan, a selective angiotensin II type 1 receptor (AT1R) antagonist, has therapeutic benefit to reverse IFP/synovial fibrosis and secondarily to attenuate pain behavior. In male Wistar rats with monoiodoacetic acid (MIA)-induced IFP/synovial fibrosis, a possible role for increased AT1R expression in the pathogenesis of IFP/synovial fibrosis was assessed over an 8-week period. Pain behavior comprised static weight bearing and von Frey paw withdrawal thresholds (PWTs), which were assessed once or twice weekly, respectively. Groups of MIA-rats received oral losartan (30-mg/kg; n = 8 or 100-mg/kg; n = 9) or vehicle (n = 9) for 28-days according to a prevention protocol. Animals were euthanized on day 28 and various tissues (IFP/synovium, cartilage and lumbar dorsal root ganglia (DRGs)) were collected for histological, immunohistochemical and western blot analyses. Administration of once-daily losartan for 28-days dose-dependently attenuated the development of static weight bearing. This was accompanied by reduced IFP/synovial fibrosis and suppression of TGF-β1 expression. Chronic treatment of MIA-rats with losartan had an anti-fibrotic effect and it attenuated pain behavior in this animal model.

Mesenchymal stem cells (MSCs)-derived exosomes have shown promise as a cell-free therapeutic strategy for neuropathic pain. This study was conducted to explore the potential mechanisms underlying the analgesic effects of MSC-derived exosomes in treating neuropathic pain.

Studies of individuals with non-cancer-related chronic pain, find that higher levels of psychological flexibility (PF) are associated with less distress, better functioning, and a better response to treatment. People diagnosed with cancer are at significantly increased risk of developing chronic cancer-related pain, the presence of which is associated with poorer health outcomes. Little is known about whether PF is applicable to cancer pain. The current study investigates the relationship between chronic cancer-related pain, distress and functioning, and three theoretical processes proposed by the PF model: pain acceptance, present-moment focus, and committed action.