Rejected

Many studies suggest opioid receptor (OPr) dimerization modulates the pharmacological properties of opiates. Specifically, heteromerization between OPr types has been reported to lead to changes in intracellular signaling. Thus, ligands targeting heteromers are expected to be novel therapeutic targets with reduced side effects. The heteromers of mu (MOPr) and delta (DOPr) are detected in brain regions involved in pain processing. The bivalent ligand or small molecule were identified as a MOPr-DOPr targeting ligand. These ligands exhibit antinociceptive properties similar to that of morphine with lesser antinociceptive tolerance as compared to morphine. Studies exploring the in vivo regulation of MOPr-DOPr heteromers, showed chronic morphine administration leads to an upregulation of these heteromers in select brain regions. Exploration of mechanisms underlying this phenomenon led us to the G protein-coupled receptor chaperone, RTP4, that is induced by chronic morphine and facilitates the heteromerization of MOPr and DOPr. In this review, I will introduce the simulated structure or property of MOPr-DOPr heteromer, its targeting ligands, and its intracellular regulatory mechanism that include a key molecule like RTP4 that could serve as a scaffold for the development of novel therapeutic drugs with reduced adverse effects, and hence may take place of the conventional clinical opioids.

Prolonged postoperative pyrexia (PPP) due to Mollaret's meningitis following endoscopic transsphenoidal surgery (eTSS) for an intracranial epidermoid cyst can be confused with postoperative meningeal infection after transsphenoidal resection, especially in the middle of the COVID-19 pandemic. Anosmia, as well as dysgeusia, cannot be evaluated in patients of eTSS for a while after surgery. We report a case of an infundibular epidermoid cyst with post-eTSS Mollaret's meningitis (MM). The post-eTSS MM caused vasopressin-analogue-resistant polyuria (VARP) in synchronization with PPP. A 59-year-old man experiencing recurrent headaches and irregular bitemporal hemianopsia over three months was diagnosed with a suprasellar tumor. The suprasellar tumor was an infundibular cyst from the infundibular recess to the posterior lobe of the pituitary, which was gross-totally resected including the neurohypophysis via an extended eTSS. Since awakening from general anesthesia after the gross total resection (GTR) of the tumor, the patient continuously had suffered from headache until the 13 postoperative day (POD13). The patient took analgesics once a day before the surgery and three times a day after the surgery until POD11. Pyrexia (37.5-39.5 degree Celsius) in synchronization with nonnephrogenic VARP remitted on POD18. Intravenous antibiotics had little effect on changes of pyrexia. Serum procalcitonin values (reference range <0.5 ng/mL) are 0.07 ng/mL on POD12 and 0.06 ng/mL on POD18. His polyuria came to react with sublingual desmopressin after alleviation of pyrexia. He left the hospital under hormone replacement therapy without newly added neurological sequelae other than hypopituitarism. After GTR of an infundibular epidermoid cyst, based on values of serum procalcitonin, post-eTSS MM can be distinguished from infection and can be treated with symptomatic treatments. The postoperative transient nonnephrogenic VARP that differs from usual central diabetes insipidus can react with sublingual desmopressin after alleviation of PPP in the clinical course of post-eTSS MM. An infundibular epidermoid cyst should be sufficiently resected in one sitting to minimize comorbidities, its recurrence, or postoperative MM to the utmost.

Pain is a common symptom among patients, and pain management is an important clinical practice topic. The mechanism of Huajiao (HJ; Maxim.) and its effective components for treating pain was explored using network pharmacology and molecular docking to verify its pain relief function in traditional medical practice.

Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury.

Pain is one of the most common causes of seeking medical care. In the day to day clinical practice, incidence of pain of some origin is next only to common cold. The average life span of an Indian has also increased and this population is vulnerable to chronic and cancer pain. Anaesthesiologists are well-versed with the art and science of treating pain and their role as pain physician is a natural extension of the professional work. 'Pain Medicine' is growing as a speciality. Last two decades have seen an explosive growth in the scientific study of pain and anaesthesiologists taking up pain medicine as a career. Postgraduate students can certainly adopt this super speciality. This article highlights the merits and depicts various aspects of 'pain medicine' as a career.

Femoral Nerve Block (FNB) and Adductor Canal Block (ACB) methods, which are regional analgesic techniques, are successfully used in postoperative pain control after total knee arthroplasty. This study aimed to compare adductor canal block method that was preoperatively used and femoral nerve block method in total knee arthroplasty (TKA) patients who underwent spinal anesthesia in terms of factors effecting patient satisfaction and determine whether these methods were equally effective or not.

Both lumbosacral plexus block (LSPB) and local infiltration analgesia (LIA) can provide postoperative analgesia for patients undergoing total hip arthroplasty (THA). The current study aimed to compare the differences between LSPB and LIA on postoperative pain and quality of life (QoL) in THA patients.

Molecular networks based on the abundance of mRNA at the gene level and pathway networks that relate families or groups of paralog genes have supported the understanding of interactions between molecules. However, multiple molecular mechanisms underlying health and behavior, such as pain signal processing, are modulated by the abundances of the transcript isoforms that originate from alternative splicing, in addition to gene abundances. Alternative splice variants of growth factors, ion channels, and G-protein-coupled receptors can code for proteoforms that can have different effects on pain and nociception. Therefore, networks inferred using abundance from more agglomerative molecular units (eg, gene family, or gene) have limitations in capturing interactions at a more granular level (eg, gene, or transcript isoform, respectively) do not account for changes in the abundance at the transcript isoform level.

Nefopam is a non-NSAIDs and opioid sparing centrally acting drug which is effective for a multimodal postoperative analgesia. The present study aimed to evaluate the analgesic efficacy of nefopam combined with parecoxib for gynecologic surgery.