YokoCo

The control of neuropathic pain is a leading challenge in modern medicine. Traditional medicine has, for a long time, used natural compounds such as nutraceuticals for this purpose, and extensive evidence has supported their role in controlling oxidative stress and persistent pain-related inflammation. Nutraceuticals are natural products belonging to the food sector whose consumption could be related to physiological benefits. Indeed, they are used to improve health, prevent chronic diseases, and delay the aging process. Here, we report a systematic review and meta-analysis to provide a more comprehensive report on the use of nutraceuticals in neuropathic pain, including evaluating confounding factors. A search of the literature has been conducted on principal databases (PubMed, MEDLINE, EMBASE, and Web of Science) following the PRISMA statement, and we retrieved 484 articles, 12 of which were selected for the meta-analysis. The results showed that administration of natural drugs in animals with neuropathic pain led to a significant reduction in thermal hyperalgesia, measured in both the injured paw (SMD: 1.79; 95% CI: 1.41 to 2.17; < 0.0001) and in the two paws (SMD: -1.74; 95% CI: -3.36 to -0.11; = 0.036), as well as a reduction in mechanical allodynia and hyperalgesia (SMD: 1.95, 95% CI: 1.08 to 2.82; < 0.001) when compared to controls. The results of the review indicate that nutraceutical compounds could be clinically relevant for managing persistent neuropathic pain.

Pain, usually caused by a strong or disruptive stimulus, is an unpleasant sensation that serves as a warning to organisms. To adapt to extreme environments, some terrestrial animals have evolved to be inherently insensitive to pain. Cetaceans are known as supposedly indifferent to pain from soft tissue injury representatives of marine mammals. However, the molecular mechanisms that explain how cetaceans are adapted to pain in response to seawater environment remain unclear. Here, we performed a molecular evolutionary analysis of pain-related genes in selected representatives of cetaceans. gene was identified to be pseudogenized in all odontocetes (toothed whales) except from (sperm whales), and relaxed selection of this gene was detected in toothed whales with pseudogenized . In addition, positive selection was detected in pain perception (i.e., , , , and ) and analgesia (i.e., , , , and ) genes among the examined cetaceans. In this study, potential convergent amino acid substitutions within predicted proteins were found among the examined cetaceans and other terrestrial mammals, inhabiting extreme environments (e.g., V441I of TRPV1 in cetaceans and naked mole rats). Moreover, specific amino acid substitutions within predicted sequences of several proteins were found in the studied representatives of cetaceans (e.g., F56L and D163A of ASIC3, E88G of GRK2, and F159L of OPRD1). Most of the substitutions were located within important functional domains of proteins, affecting their protein functions. The above evidence suggests that cetaceans might have undergone adaptive molecular evolution in pain-related genes through different evolutionary patterns to adapt to pain, resulting in greater sensitivity to pain and more effective analgesia. This study could have implications for diagnosis and treatment of human pain.

The transversus abdominis plane (TAP) block causes desensitization of the abdominal wall and peritoneum. Of all the approaches proposed to perform it, the two-injection-point TAP showed the best results in terms of the area reached by the anesthetic solution. However, to date, no clinical data exist. The aim of this study was to evaluate the intra- and postoperative analgesic efficacy of a two-injection-point TAP block in dogs undergoing laparoscopic ovariectomy. A total of 26 animals were assigned to receive general inhalation anesthesia (control group), and 26 dogs were assigned to general inhalation anesthesia combined with TAP block (TAP group). The ultrasound-guided TAP block was carried out with a subcostal and cranial-to-ilium injection per hemiabdomen. The end-tidal concentration of isoflurane (EtISO) was recorded at different moments during the surgery. Postoperative pain was assessed at different time points during the first 24 h after surgery. The control group required significantly higher EtISO concentration during the ovarian resection and showed higher postoperative pain scores than the TAP group. Fewer dogs in the TAP group required intra- or postoperative rescue analgesia. TAP block can be implemented to improve postoperative pain management after laparoscopy, reducing the dosage of the systemic drugs used and, hence, their possible side effects.

Colic, a condition affecting the gastrointestinal tract of horses, manifests as severe pain and may be a life-threatening condition. It is possible to distinguish between an acute, disposable process, as well as recurrent colic symptoms (abdominal pain) caused by an ongoing chronic inflammatory process. This paper presents a retrospective analysis of the histopathological findings of duodenal and rectal samples taken from horses with recurrent colic, with the aim to determine the frequency and extent of inflammation. The samples, i.e., duodenal biopsy (60 samples) and rectal biopsy (17 samples), were taken from 77 horses showing recurrent colic symptoms. Histopathological examination included staining with hematoxylin and eosin. The examination included evaluation of the superficial epithelium, mucosal lamina propria, and submucosa. All samples from the duodenum and rectum showed the presence of leukocyte infiltration in the mucosal lamina propria. The most frequently observed cellular infiltration was a moderate infiltration consisting of lymphocytes and plasma cells in duodenum and mixed populations of plasma cells, lymphocytes, and eosinophilia in the rectum. Mott cells were also noted among the inflammatory infiltrates. More than one-fourth of the horses were found to have shortened intestinal villi. The results presented here showed the involvement of inflammation in the course of recurrent colic, which can be both its cause (by impairing motility and absorption) and its effect (as a result of obstruction or ischemia).

Nocebo effects are thought to influence the rate of reported adverse events (AEs) and subject withdrawal in both the treatment and placebo groups of randomized clinical trials (RCTs). Neuromodulators are commonly prescribed to treat disorders of gut-brain interaction (DGBIs), but adherence to these medications is often limited by side effects such as headache, dry mouth, fatigue, and altered bowel habits. We performed a systematic review and meta-analysis to assess the proportion and risk difference of patients who experienced side effects leading to withdrawal in the placebo arm versus the treatment arm of RCTs of neuromodulators for DGBIs. We also sought to estimate the risk of developing any AE in the placebo arm of these studies as well as the rate of specific individual adverse events.

Evaluation of drug safety during pregnancy is dependent on the number of exposed women during routine clinical practice with data available for analysis. We examined medication fills in pregnant and nonpregnant women within select disease cohorts: general population, migraine, diabetes, and hyperlipidemia to explore the potential use of claims data to assess medication use and safety during pregnancy.

Meniere's disease (MD) represents one of the vertigo disorders characterized by triad symptoms (recurrent vertigo, fluctuating hearing loss, tinnitus or ear fullness). The diagnosis of MD relies on the accurate and detailed taking of medical history, and the differentiation between MD and vestibular migraine (VM) is of critical importance from the perspective of the treatment efficacy. VM is a highly prevalent vertigo condition and its typical symptoms (headache, vestibular symptoms, cochlear symptoms) mimic those of MD. Furthermore, the misdiagnosis in MD and VM could lead to VM patients mistakenly receiving the traumatic treatment protocol designed for MD, and sustaining unnecessary damage to the inner ear. Fortunately, thanks to the advances in examination technologies, the barriers to their differentiation are being gradually removed. These advances enhance the diagnostic accuracy of vertigo diseases, especially VM and MD. This review focused on the differentiation of VM and MD, with an attempt to synthesize existing data on the relevant battery of differentiation diagnosis (covering core symptoms, auxiliary tests [audiometry, vestibular tests, endolymphatic hydrops tests]) and longitudinal follow-up. Since the two illnesses are overlapped in all aspects, no single test is sufficiently specific on its own, however, patterns containing all or at least some features boost specificity.

To examine the effects of photobiomodulation (PBM) in healthy volunteers using photonic stimulation of acupuncture points on conditioned pain modulation (CPM), temporal summation of pain (TSP), and offset analgesia (OA), which reflect some aspects of endogenous pain modulation. We included 15 men and 15 women (age, 31.5 [27.3-37.0], body mass index, 25.7 [24.4-27.1], Fitzpatrick skin typing, II: 20, III: 8, IV: 2). CPM, TSP, and OA were evaluated after a sham procedure (control session) and after acupuncture point stimulation (LI4 and LI10 on the non-dominant forearm) using linear polarized near-infrared light irradiation (LPNILI; wavelengths peaked at approximately 1000 nm, output: 1.4 W/cm, spot diameter: 10 mm, spot size: 1.02 cm, maximum temperature: 40.5 °C, pulse width: 1 s, frequency: 0.2 Hz) (PBM session). Differences in CPM, TSP, and OA between the two sessions were evaluated by the paired t-test and Fisher's exact test (statistical significance: p < 0.05). Values indicate median [interquartile range]. LPNILI significantly increased CPM in all participants (control session: 12.1 [-4.5-37.4], PBM session: 23.9 [8.3-44.8], p < 0.05) and women (control session: 16.7 [-3.4-36.6], PBM session: 38.7 [24.6-52.1], p < 0.05). The CPM effect increment was significantly higher in women than in men (p = 0.0253). LPNILI decreased TSP in participants with higher TSP ratios (p = 0.0219) and increased OA in participants with lower OA scores (p = 0.0021). LPNILI enhanced endogenous pain modulation in healthy volunteers, particularly in women, as evaluated using CPM. CPM, TSP, and OA evaluations are potentially useful for discriminating PBM responders from non-responders.

We describe a case of chronic tophaceous gout affecting the spine, hands, elbows, feet, and knees in a 67-year-old man with serum urate levels at 549 µmol/L whose response to treatment was successfully mapped using dual-energy computed tomography (DECT). The patient presented with exacerbation of acute-on-chronic lumbar back pain. He had received a diagnosis of gout 3 years prior to this presentation yet was not on any urate-lowering therapy. The patient received febuxostat 80 mg and colchicine 0.3 mg once daily and underwent DECT to assess baseline monosodium urate (MSU) burden. At baseline, MSU deposits were seen in the hands, elbows, feet, knees, and lumbar spine including the left L5-S1 facet joint encroaching onto the neural foramen. After 2.5 years of treatment, serum urate level was within the target range (< 360 µmol/L), and the patient underwent a follow-up DECT that revealed almost full resolution of MSU deposition in the spine, including the MSU-burdened facet joint and neural foramen in the lumbar spine, in addition to all the affected peripheral joints. This case is the first report of radiological evidence of nearly complete resolution of MSU deposits in spinal gout on DECT after urate-lowering therapy treatment, which demonstrates the utility of this imaging modality as a non-invasive investigational point-of-care imaging modality for mapping treatment response and identifying the etiology of back pain in a patient with chronic tophaceous spinal gout.

Neuropathic pain arises from injuries to the nervous system. It affects 20% of the adult US population and poses a major socioeconomic burden yet remains exceedingly difficult to treat. Current therapeutic approaches have limited efficacy and a large side effect profile that impedes their ability to treat neuropathic pain effectively. Preclinical research over the last 30 yr has established the critical role that pro-inflammatory neuro-immune cell interactions have in the development and maintenance of neuropathic pain arising from various etiologies. Pro-inflammatory neuro-immune cell interactions also underlie the development of adverse side effects of opioids and the loss of their efficacy to treat pain. Evidence from work in our lab and others in preclinical animal models have shown that signaling from the bioactive sphingolipid, sphingosine-1-phosphate (S1P), through the S1P receptor subtype 1 (S1PR1) modulates neuro-immune cell interactions. Here, we discuss how targeting S1P/S1PR1 signaling with S1PR1 antagonists already Food and Drug Administration-approved or in clinical trials for multiple sclerosis can provide a viable pharmacotherapeutic approach to reduce neuro-immune cell inflammatory signaling and potentially treat patients suffering neuropathic pain and the adverse effects of opioids.