Rejected

Neutrophils are peripheral immune cells that represent the first recruited innate immune defense against infections and tissue injury. However, these cells can also induce overzealous responses and cause tissue damage. Although the role of neutrophils activating the immune system is well established, only recently their critical implications in neuro-immune interactions are becoming more relevant. Here, we review several aspects of neutrophils in the bidirectional regulation between the nervous and immune systems. First, the role of neutrophils as a diffuse source of acetylcholine and catecholamines is controversial as well as the effects of these neurotransmitters in neutrophil's functions. Second, neutrophils contribute for the activation and sensitization of sensory neurons, and thereby, in events of nociception and pain. In addition, nociceptor activation promotes an axon reflex triggering a local release of neural mediators and provoking neutrophil activation. Third, the recruitment of neutrophils in inflammatory responses in the nervous system suggests these immune cells as innovative targets in the treatment of central infectious, neurological and neurodegenerative disorders. Multidisciplinary studies involving immunologists and neuroscientists are required to define the role of the neurons-neutrophils communication in the pathophysiology of infectious, inflammatory, and neurological disorders.

Postmenopausal osteoporosis is one of the most common types of osteoporosis resulting from estrogen deficiency in elderly women. Nonsteroidal anti-inflammatory drugs (NSAIDs) are important drugs for pain relief in patients with osteoporosis. In this study, we report for the first time that flufenamic acid, a clinically approved and widely used NSAID, not only has analgesic properties but also shows a significant effect in terms of preventing postmenopausal osteoporosis. Quantitative RT-PCR analysis showed that treatment with flufenamic acid significantly downregulated the genes associated with osteoclast differentiation. Meanwhile, RNA-sequencing and western blot analyses suggested that flufenamic acid could inhibit the bone resorption by suppressing the phosphorylation of MAPK pathways. Moreover, an ovariectomy (OVX)-induced bone-loss mouse model indicated that flufenamic acid might be a potent drug for preventing osteoporotic fractures, as verified by micro-CT scanning and histological analysis. Therefore, this study proposes an attractive and potent drug with analgesic properties for the prevention of postmenopausal osteoporosis.

Abdominal pain is a common cause for emergency department visits in the United States, and biliary tract disease is the fifth most common cause of hospital admission. Common causes of acute hepatobiliary include gallstones and its associated complications and multiple other hepatobiliary etiologies, including infectious, inflammatory, vascular, and neoplastic causes. Postoperative complications of the biliary tract can result in an acute abdomen. Imaging of the hepatobiliary tree is integral in the diagnostic evaluation of acute hepatobiliary dysfunction, and imaging of the biliary tree requires a multimodality approach utilizing ultrasound, computed tomography, nuclear medicine, and MR imaging.

The root of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, was mainly used in ancient times in the treatment of urinary calculi, recurrent headache and joint pain.

Podcast recording of Editorial Board Members Uazman Alam and Shazli Azmi live from the EASD 2019 conference in Barcelona (MP4 377292 kb).

JWH-018-Cl, JWH-018-Br and AM-2201 (JWH-018 halogenated-derivatives; JWH-018-R compounds) are synthetic cannabinoid agonists illegally marketed as "Spice", "K2", "herbal blend" and research chemicals for their cannabis-like psychoactive effects. In rodents, JWH-018 and its halogenated derivatives reproduce the typical effects of Δ-tetrahydrocannabinol (Δ-THC), i.e. hypothermia, analgesia, hypolocomotion and akinesia. Yet, the effects of JWH-018-R compounds on sensorimotor functions are still unknown. This study was designed to investigate the effect of an acute intraperitoneal (i.p.) administration of JWH-018-R compounds (0.01-6 mg/kg) on sensorimotor functions in mice and to compare them to those caused by the reference compound JWH-018 and Δ-THC. A well validated battery of behavioral tests was used to investigate the effects of these synthetic cannabinoids on the visual, auditory and tactile responses in mice, while the pre-pulse inhibition (PPI) test was used to investigate their effect on sensorimotor gating. The effect of the synthetic cannabinoids on spontaneous locomotion was also measured by a video tracking analysis to assess potential cannabinoid-induced motor impairment. Results showed that, similarly to JWH-018, systemic administration of JWH-018-R compounds inhibits sensorimotor and PPI responses at lower doses (0.01-0.1 mg/kg) and reduced spontaneous locomotion at intermediate/high doses (1-6 mg/kg). All effects were prevented by the administration of the selective cannabinoid CB receptor antagonist/inverse agonist AM-251 thus confirming a CB receptor-mediated action. Finding that lower doses of JWH-018-R compounds selectively impair sensorimotor and PPI responses without affecting locomotion should be carefully considered to better understand the potential danger that halogenated-derivatives of JWH-018 may pose to public health, with particular reference to decreased performance in driving and hazardous works.

Individuals with inflammatory bowel disease (IBD) are commonly diagnosed when they are between the ages of 18-29, a developmental period known as emerging adulthood. Typically, emerging adults are subsumed into the category of adults even though emerging adults have unique developmental needs. In this descriptive study of IBD in emerging adults, the aims were to (a) determine the prevalence of symptoms; (b) describe the severity of symptoms and their interference with daily activities; and (c) examine the association between individual symptom severity and presence of fatigue. Emerging adults with IBD were recruited using web-based convenience sampling. Sixty-one individuals met the inclusion criteria. They had a mean age of 24.7 and a disease duration of 6.4 years. The most prevalent symptoms reported were: fatigue (n = 44, 72.1%), abdominal cramps (n = 39, 63.9%), abdominal pain (n = 39, 63.9%), and diarrhea (n = 38, 62.3%). The symptom with the greatest severity and interference with daily activities was fatigue. Abdominal cramps, abdominal pain, diarrhea, passing gas, and abdominal tenderness were associated with fatigue when controlling for age, emerging adulthood, gender, time since diagnosis, and current steroid use. Among emerging adults with IBD, fatigue is the most prevalent symptom and is the symptom with the greatest severity and interference with daily activities. These results suggest a need for interventions aimed at reducing both fatigue and gastrointestinal symptoms among emerging adults with IBD.

The primary objective of this study was to investigate the effects of Pulsed RF application in the genicular nerve on pain and function in patients with osteoarthritis (OA) and its side effects.

Yokukansan is a traditional Japanese herbal medicine that has an antiallodynic effect in patients with chronic pain. However, the mechanisms by which yokukansan inhibits neuropathic pain are unclear.

To investigate the 20-year relationship between anxiety, depression and pain medication use. A total of 521 individuals reporting chronic pain from the National Survey of Midlife Development in the USA (MIDUS) study. Structural equation modeling of 20-year longitudinal survey data. Over 20 years, a bidirectional relationship between depression and anxiety in individuals with chronic pain was indicated. Pain medication utilization predicted later use at 10 years. Pain medication use was not strongly related to later anxiety; however, heightened anxiety was associated with later use. Depression and anxiety show an extensive long-term bidirectional relationship. While there was little indication of a relationship between pain medication use and later negative mood, anxiety was associated with subsequent pain medication use.