Accepted

Rheumatoid arthritis is a chronic autoimmune disease that mainly affects the facet joints. Elderly-onset rheumatoid arthritis appears to exhibit symptoms similar to those of polymyalgia rheumatica, characterized by morning stiffness and pain in the shoulder and hip joints. Both diseases develop in the elderly, and it is sometimes challenging to distinguish them. Here, we identify the differences in pathogenesis between elderly-onset rheumatoid arthritis and polymyalgia rheumatica to assist with a clear differential diagnosis and effective early intervention.

In patients with sickle cell disease (SCD), negative physical and emotional experiences result from intense chronic and acute pain episodes, but factors underlying these, and their interactions, are not well understood. The arginine vasopressin receptor 1a gene () single nucleotide polymorphism rs10877969 has been previously associated with aspects of acute pain and stress related pain. In this study, we tested for associations between this SNP, thermal and pressure pain thresholds, clinical pain, and stress in people with SCD.

One social mechanism by which marginalization is enacted is via ostracism. Recent research has demonstrated ostracism's impact on physical health, but little is known about the relationship between accumulated lifetime experiences of ostracism and pain. Despite recent calls for added attention to social modulation of pain and social indicators of pain disparities, the impact of specific social factors on pain-including those of ostracism-are not well understood. Results of laboratory studies on the effects of acute ostracism experiences on pain sensitivity have been mixed. However, these studies have not considered lived and repeated experiences of ostracism, and primarily included single static measures of pain sensitivity. Additionally, inclusion and representation of the relationship between ostracism experiences and pain among people with minoritized identities are lacking in the current literature. In this study, we explored accumulated lifetime experiences of ostracism as a potential contributing factor to enhanced pain and one social mechanism by which societal inequity may create and maintain inequity in pain. We extracted measures of lifetime experiences of ostracism from six studies focused on social factors and (non-chronic) pain conducted between 2016 and 2020 ( = 505 adults). To retain and examine diversity within the sample, we used moderation and within-group analyses. Results indicate that greater experiences of lifetime ostracism are associated with lower cold pain tolerance, but not other pain measures, in the whole sample. Moderation and within-group analyses reveal opposing patterns of results between populations included in the extant literature (White participants, convenience samples) and those under-represented in the scientific literature (racialized groups, community samples). This study provides an example of a diversity science approach to examining social indicators of pain, illustrates the limited generalizability of previous studies on ostracism and pain, and highlights the need for increased representation and inclusion to understand mechanisms of pain and inequity.

Musculoskeletal spinal disorders significantly impact patient populations from everyday workers to military soldiers. Effective treatment is critical to minimize the time between injury and returning to work and daily activities. Injection of amniotic membrane/umbilical cord (AMUC) tissue has demonstrated great potential in reducing patients' pain and has become an increasingly popular treatment option for painful orthopedic disorders.

Despite the prevalence of opioid misuse, opioids remain the frontline treatment regimen for severe pain. However, opioid safety is hampered by side-effects such as analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, or reward. These side effects promote development of opioid use disorders and ultimately cause overdose deaths due to opioid-induced respiratory depression. The intertwined nature of signaling via μ-opioid receptors (MOR), the primary target of prescription opioids, with signaling pathways responsible for opioid side-effects presents important challenges. Therefore, a critical objective is to uncouple cellular and molecular mechanisms that selectively modulate analgesia from those that mediate side-effects. One such mechanism could be the transactivation of receptor tyrosine kinases (RTKs) via MOR. Notably, MOR-mediated side-effects can be uncoupled from analgesia signaling via targeting RTK family receptors, highlighting physiological relevance of MOR-RTKs crosstalk. This review focuses on the current state of knowledge surrounding the basic pharmacology of RTKs and bidirectional regulation of MOR signaling, as well as how MOR-RTK signaling may modulate undesirable effects of chronic opioid use, including opioid analgesic tolerance, reduced analgesia to neuropathic pain, physical dependence, and reward. Further research is needed to better understand RTK-MOR transactivation signaling pathways, and to determine if RTKs are a plausible therapeutic target for mitigating opioid side effects.

Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

The dynamic vascular responses during cortical spreading depolarization (CSD) are causally related to pathophysiological consequences in numerous neurovascular conditions, including ischemia, traumatic brain injury, cerebral hemorrhage, and migraine. Monitoring of the hemodynamic responses of cerebral penetrating vessels during CSD is motivated to understand the mechanism of CSD and related neurological disorders. Six SD rats were used, and craniotomy surgery was performed before imaging. CSDs were induced by topical KCl application. Ultrasound dynamic ultrafast Doppler was used to access hemodynamic changes, including cerebral blood volume (CBV) and flow velocity during CSD, and further analyzed those in a single penetrating arteriole or venule. The CSD-induced hemodynamic changes with typical duration and propagation speed were detected by ultrafast Doppler in the cerebral cortex ipsilateral to the induction site. The hemodynamics typically showed triphasic changes, including initial hypoperfusion and prominent hyperperfusion peak, followed by a long-period depression in CBV. Moreover, different hemodynamics between individual penetrating arterioles and venules were proposed by quantification of CBV and flow velocity. The negative correlation between the basal CBV and CSD-induced change was also reported in penetrating vessels. These results indicate specific vascular dynamics of cerebral penetrating vessels and possibly different contributions of penetrating arterioles and venules to the CSD-related pathological vascular consequences. We proposed using ultrasound dynamic ultrafast Doppler imaging to investigate CSD-induced cerebral vascular responses. With this imaging platform, it has the potential to monitor the hemodynamics of cortical penetrating vessels during brain injuries to understand the mechanism of CSD in advance.