Rejected

Osteoclasts are unique and vital bone cells involved in bone turnover. These cells are active throughout the individual's life and play an intricate role in growth and remodeling. However, extra-label bisphosphonate use may impair osteoclast function, which could result in skeletal microdamage and impaired healing without commonly associated pain, affecting bone remodeling, fracture healing, and growth. These effects could be heightened when administered to growing and exercising animals. Bisphosphonates (BPs) are unevenly distributed in the skeleton; blood supply and bone turnover rate determine BPs uptake in bone. Currently, there is a critical gap in scientific knowledge surrounding the biological impacts of BP use in exercising animals under two years old. This may have significant welfare ramifications for growing and exercising equids. Therefore, future research should investigate the effects of these drugs on skeletally immature horses.

To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy and safety of isosorbide mononitrate (IMN) in promoting cervical ripening during labour induction.

Hypermobile Ehlers Danlos Syndrome (hEDS)/hypermobility spectrum disorders (HSD) are incapacitating and painful syndromes involving a generalized connective tissue disorder with joint hypermobility and musculoskeletal complications. A neuropathic component is clinically likely given frequent burning sensations, hypoesthesia, or allodynia. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A-I and C-fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series Na20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing. In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data.A small fiber neuropathy was definite (both abnormal IENFD and QST) in 40/69 patients (58%), possible (one abnormal test) in 23/69 patients (33%) and excluded (both normal) in only 6/69 patients (9%). These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research. This article is protected by copyright. All rights reserved.

Commonly utilized pain therapeutics like opioid medications exert dangerous side effects and lack effectiveness in treating some types of pain. Ketamine is also used to treat pain, but side effects limit its widespread use. (2,6)-hydroxynorketamine (HNK) is a ketamine metabolite that potentially shares some beneficial behavioral effects of its parent drug without causing significant side effects. This study compared the profile and potential mechanisms mediating the antinociception activity of ketamine and (2,6)-HNK in C57BL/6J mice. Additionally, this study compared the reversal of mechanical allodynia by (2,6)-HNK with gabapentin in a model of neuropathic pain. Unlike the near-immediate and short-lived antinociception caused by ketamine, (2,6)-HNK produced late-developing antinociception 24 hours following administration. Pharmacological blockade of AMPA receptors with NBQX prevented the initiation and expression of (2,6)-HNK antinociception, suggesting the involvement of AMPA receptor-dependent glutamatergic mechanisms in the pain reduction-like responses. Blockade of opioid receptors with naltrexone partially prevented the antinociceptive effect of ketamine but was ineffective against (2,6)-HNK. Furthermore, (2,6)-HNK did not produce dystaxia, even when tested at doses five times greater than those needed to produce antinociception, indicating a superior safety profile for (2,6)-HNK over ketamine. Additionally, (2,6)-HNK reversed mechanical allodynia in an SNI model of neuropathic pain with similar short-term efficacy to gabapentin (within 4 hours) while outperforming gabapentin 24 hours after administration. These findings support the further study of (2,6)-HNK as a potentially valuable agent for treating different types of pain and establish certain advantages of (2,6)-HNK treatment over ketamine and gabapentin in corresponding assays for pain. The ketamine metabolite (2,6)-HNK produced antinociception in male and female mice 24 hours after administration via activation of AMPA receptors. The effects of (2,6)-HNK differed in time course and mechanism and presented a better safety profile than ketamine. (2,6)-HNK also reversed allodynia in SNI-operated animals within 4 hours of treatment onset, with a duration of effect lasting longer than gabapentin. Taken together, (2,6)-HNK demonstrates the potential for development as a non-opioid analgesic drug.

We investigated the classification of diabetic peripheral neuropathy (DPN) patients by subjective symptoms and identification of the relationship between the patterns and intensities of symptoms and the clustered groups of DPN patients.

Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL.

This randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210-a linear peptide derived from subcommissural organ-spondin-and explored the effects on blood/urine biomarkers and cerebral activity.

This study's purpose was to determine if ondansetron can prevent pruritus after administration of intrathecal morphine in children, as has been demonstrated in adults.

Postherpetic neuralgia (PHN) is a painful condition that persists for 1 month or more after herpes zoster rash has healed. Radiofrequency thermocoagulation (RF-TC) provides analgesia by destroying the dorsal root ganglion and blocking the pain upload pathway; nonetheless, the concomitant neurological-related side effects and recurrence remain a concern.

In this randomized, blinded study, we evaluated the effects of different programmed intermittent epidural bolus (PIEB) volumes for labor analgesia on the incidence of breakthrough pain and other analgesic outcomes.