Accepted

Global cerebral ischemia/reperfusion (I/R) provokes inflammation that augments neuropathic pain. Cilostazol (CLZ) has pleiotropic effects including neuroprotection in several ravaging central disorders; nonetheless, its potential role in transient central ischemic-induced allodynia and hyperalgesia has not been asserted before. Rats were allocated into 4 groups; sham, sham + CLZ, and 45 min-bilateral carotid occlusion followed by a 48 h-reperfusion period either with or without CLZ (50 mg/kg; p.o) post-treatment. CLZ prolonged latency of hindlimb withdrawal following von Frey filaments, 4 °C cold, and noxious mechanical stimulations. Histopathological alterations and the immunoexpression of glial fibrillary acidic protein induced by I/R were reduced by CLZ in the anterior cingulate cortex (ACC) area, while, CLZ enhanced intact neuronal count. Meanwhile, CLZ modulated cerebral cortical glutamate, dopamine neurotransmission, and transient receptor potential ankyrin 1 (TRPA1). CLZ anti-inflammatory potential was mediated by the downregulated p65 NF-κB and sirtuin-1 enhancement to reduce nucleotide-binding domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), active caspase-1, and interleukin-1β, indicative of inflammasome deactivation. It also revealed an antioxidant capacity via boosting nuclear factor E2-related factor (Nrf2) enhancing glutathione through forkhead box protein O3a (FOXO3a) reduction. Additionally, CLZ triggered neuronal survival by promoting the p-content of Akt, TrkB, and CREB as well as BDNF content. A novel approach of CLZ in hindering global cerebral I/R-mediated neuropathy is firstly documented herein to forward its adjunct action via deactivating the NLRP3 inflammasome, besides enhancing Nrf2 axis, neuronal survival, and dopamine neurotransmission as well as inhibiting TRPA1 and excitotoxicity.

Abdominal pain, which is a form of visceral pain, is a highly prevalent symptom worldwide frequently occurring following food ingestion. Its pathophysiology is complex and many factors, including intestinal environmental cues, the immune system, or the molecular composition of foods, can influence the development of postprandial abdominal pain. Due to the poor efficacy of drug treatments, current strategies are often limited to the exclusion of culprit food(s) from the diet. However, there are two important limitations to this approach. Firstly, patients suffering from food-induced abdominal pain usually recognise several food items as the cause of their gastrointestinal symptoms. Secondly, not all offending foods can always be identified by these patients. Newly identified mechanisms involving neuro-immune interactions and their communication with the intestinal microbiota shed light on the development of new therapeutic strategies. In this Mini-review, I highlight these novel mechanisms and discuss the relevance of such findings.

Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis.

Alcohol use disorder (AUDs) commonly co-occurs in patients with chronic pain, and a major barrier to achieving abstinence and preventing relapse is the emergence of hyperalgesia during alcohol withdrawal. Elucidating novel therapeutic approaches to target hyperalgesia associated with alcohol withdrawal could have important implications for the treatment of AUD. Here we examined the role of 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid (eCB) signaling in the regulation of hyperalgesia associated with alcohol withdrawal in mice and tested the hypothesis that pharmacological augmentation of 2-AG signaling could reduce hyperalgesia during withdrawal.

Chronic pain is a multifaceted disorder genuinely entangled with psychic and psychosomatic symptoms, which are typically involved in the processes of chronification. The impingement syndrome of the shoulder is no exception to this rule, but several studies have shown respective peculiarities among those with pain and impingement of the shoulder. Notably, chronic pain is a lateralized experience, and, similarly, its psychosomatic correlates may be attached to the hemispheres functionally.

To explore the clinical value of ultrasound combined with C-arm guiding selective semilunar ganglion radiofrequency thermocoagulation via the foramen ovale for trigeminal neuralgia.