Rejected

TRPV1 are involved in the control of the gastrointestinal (GI) functions and pain sensation. Their activation induces pain but it is followed by desensitization, which in turn causes analgesia. The studies from the last two decades indicate that TRPV1 are involved in visceral hypersensitivity in the GI tract and pathogenesis of irritable bowel syndrome (IBS). Therefore, the aim of this study is to assess the action of fast desensitizing agonist of TRPV1, palvanil (N-palmitoyl-vanillamine), in the murine GI tract and on nociception to evaluate its potential application in the therapy of IBS. The effect of palvanil on smooth muscle contractility was evaluated using organ baths. The impact of palvanil on intestinal secretion was assessed in Ussing chambers. In vivo, the action of palvanil (0.1-1 mg/kg) was assessed in whole GI transit, fecal pellet output, and colonic bead expulsion tests. The antinociceptive potency of palvanil was tested in the mustard oil-induced pain test. Palvanil inhibited colonic contractions (evoked by electrical field stimulation, EFS) and decreased the ion transport in the colon stimulated with forskolin. It did not affect secretion in experiments with veratridine. In vivo, palvanil prolonged whole GI transit at all doses tested. At the lower dose tested, it accelerated colonic motility during first 60 min following injection. By contrast, at the dose of 1 mg/kg, colonic motility was inhibited. Palvanil induced antinociceptive action at all tested doses in mustard oil-induced pain test. TRPV1 fast-desensitizing compounds, i.e., palvanil, may be promising agents in the therapy of IBS since it modulates intestinal motility and reduces visceral pain.

Inguinal hernia repair is one of the most commonly performed surgical procedures. Postoperative neuropathic groin pain is a potentially disabling complication and can be due to a neuroma of the ilioinguinal, iliohypogastric, and/or genitofemoral nerves. In this article, we present our operative technique-a retroperitoneal approach to the ipsilateral ilioinguinal, iliohypogastric, and genitofemoral nerves with neurectomy and proximal transposition of these nerves-for management of neuropathic pain. A retrospective review was performed of 12 of the patients who underwent this surgery at our institution. Three of 12 patients underwent a selective neurectomy, whereas 9 of 12 underwent a triple neurectomy; 3 of the 9 patients who underwent triple neurectomy also had a retroperitoneal peripheral nerve stimulator placed at the time of neurectomy. Pain visual analog scores (VASs) demonstrated significant improvement after neurectomy (preoperative pain VAS of 85 ± 11 vs postoperative pain VAS of 47 ± 32, P = 0.0027). Eight of 12 patients experienced partial or complete pain relief, whereas 4 of 12 patients had no pain relief. There were no major complications, and the minor complication rate was low for all patients and primarily related to peripheral nerve stimulator placement. This retroperitoneal approach to triple neurectomy for treatment of refractory groin pain in postoperative inguinal hernia repair patients is safe and effective for an otherwise devastating problem.

Ketamine is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor which also interacts with various other receptors that account for its myriad actions. Originally approved as a general anesthetic, it is being explored to be repurposed for numerous other indications such as depressive disorders, suicidal ideation, substance-use disorders, anxiety disorders, chronic pain, refractory status epilepticus, and bronchial asthma exacerbations. Numerous trials are ongoing for the same. The nasal spray of esketamine, a more potent S (+) enantiomer of ketamine, has been approved by the United States Food and Drug Administration (USFDA) for treatment-resistant depression along with the oral antidepressants. However, there are concerns about its safety on long term use, given its psychedelic effects and potential abuse. In this review, we discuss repurposing ketamine for potential therapeutic use and about the safety concerns related to ketamine and esketamine.

Brain function relies on the capacity of neurons to locally modulate each other at the level of synapses. Therefore, the exosomal pathway may constitute a well-designed mechanism for local and systemic interneuronal transfer of information within functional brain networks. Exosomes bind to and are endocytosed by neurons of different brain regions to play a definite role. The medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) brain regions are known to involve in pain modulation. Our study observes the roles of exosomal activity in these two dominant regions of the pain-related pathway, and there influence on the analgesic effects in CCI mice.

To evaluate the pharmacokinetic profile and tolerability of pitolisant, a selective histamine 3 (H)-receptor antagonist/inverse agonist, in children and adolescents with narcolepsy.

Osteoarthritis (OA) is a painful intractable disease that significantly affects patients' quality of life. However, current therapies, such as pain killers and joint replacement surgery, do not lead to cartilage protection. Mesenchymal stem cells (MSCs) have been proposed as an alternative strategy for OA therapy because MSCs can secrete chondroprotective and anti-inflammatory factors. However, interleukin-4 (IL-4), a potent anti-inflammatory cytokine, is barely produced by MSCs, and MSC therapy suffers from rapid MSC death following intra-articular implantation. MSCs in spheroids survive better than naïve MSCs in vitro and in vivo. IL-4-transfected MSCs in spheroids (IL-4 MSC spheroid) show increased chondroprotective and anti-inflammatory effects in an OA chondrocyte model in vitro. Following intra-articular implantation in OA rats, IL-4 MSC spheroids show better cartilage protection and pain relief than naïve MSCs. Thus, IL-4 MSC spheroid may potentiate the therapeutic efficacy of MSCs for OA.

To examine the rate of new and persistent opioid use after endocrine surgery operations SUMMARY OF BACKGROUND DATA:: A global epidemic of opioid misuse and abuse has been evolving over the past 2 decades with opioid use among surgical patients being a particularly difficult problem. Minimal data exists regarding opioid misuse after endocrine surgical operations.

To review the literature for the safety and efficacy of intralesional 5-fluorouracil (5-FU) in the management of oculofacial scars.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR).

Double pylorus is one of the rare endoscopic findings consisting of two communication channels between the gastric antrum and the first part of the duodenum. It has no specific signs and symptoms. It is usually detected incidentally during endoscopic examination performed with nonspecific dyspeptic complaints such as epigastric pain, nausea, vomiting, and bloating. But contrary to expectations our patient applied to the emergency department with the complaint of melena that had been going on for 3 days. Her hemoglobin value was 9.7 mg/dL, blood ure nitrogen value was 65 mg/dL. Rectal touch examination was compatible with melena. In the emergency endoscopy of the patient, two channels were seen in the pylorus region. In the accessory canal, there was an ulcer of 10 mm in size with adherent dots and white exudate. The biopsy was reported as chronic gastritis due to H.pylori infection. Ibuprofen treatment used by the patient was discontinued and the patient was given high double dose PPI and H.pylori eradication therapy. Double pylorus, which is usually found incidentally in endoscopy with nonspecific findings, may very rarely present with GI bleeding findings, as in our patient. It is necessary to avoid risk factors in double pylorus, to give antiulcer and H.pylori treatment in its presence for an optimal time regardless of whether the double pylorus continues or not.