Rejected

In Japan, 14 opioids with a variety of dosage forms, such as oral preparation, injection, transdermal patch, transmucosal and suppository are clinically available as analgesics, and their use properly depends on the type and degree of pain and patient condition. Fundamentally, strong opioids are restricted to only treatment of cancer pain, while the indication of fentanyl transdermal patch and oxycodone tamper resistant tablet has been expanded for the treatment of non-cancer chronic pain. In US, the additional indication of opioids to chronic pain has led to prolongation and generalization of opioid use, which may contribute to "opioid crisis" in which opioid-related death strikingly increased due to opioid abuse and overdose-induced respiratory depression. Currently, opioid-related abuse and death have not been evident in Japan, while abuse of antitussive opioids (codeine and dihydrocodeine) are recently seen as a problem, which may suggest the sense of guilt to abuse legally-uncontrolled drugs (ex. weak opioids, antitussives or hypnotics) may be low in Japanese. In this review, I will summarize current status and issues in clinical use of opioid analgesics, and will talk about the necessity and expectation for development of novel analgesics without serious adverse reactions such as addiction and respiratory depression.

Traumatic spinal cord injury (SCI) causes severe motor dysfunction and persistent central neuropathic pain (Nep), which has not yet been effectively cured. Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and contributes to the immune-suppressive in tumor microenvironment. However, the role of PD-L1 in regulating inflammatory response and Nep after SCI remains unclear. A growing amount of researches have begun to investigate the effect of PD-L1 on macrophages and microglia in recent years. Considering the pivotal role of macrophages/microglia in the inflammatory response after SCI, we proposed the hypothesis that PD-L1 improved the recovery of locomotor and sensory functions after SCI through regulating macrophages and microglia.

The root of C. Y. Cheng et T. M. Ai is traditionally used as an analgesic and anti-inflammatory agent to treat pain, rheumatoid arthritis, and bone fractures. However, neither its effects on osteoarthritis (OA) nor its effects on the arthritic cartilage tissue transcriptome have not been fully investigated. In this study, we used a rat model of monosodium iodoacetate- (MIA-) induced OA to investigate the therapeutic effects of a ethanolic extract (DAE, 200 mg/kg for 21 days). The study first assessed joint diameter, micro-CT scans, and histopathological analysis and then conducted gene expression profiling using RNA sequencing in articular cartilage tissue. We found that DAE treatment ameliorates OA disease phenotypes; it reduced the knee joint diameter and prevented changes in the structural and histological features of the joint, thereby showing that DAE has a protective effect against OA. Based on the results of gene expression profiling and subsequent pathway analysis, we found that several canonical pathways were linked to DAE treatment, including WNT/β-catenin signaling. Taken together, the present results suggest molecular mechanism, involving gene expression changes, by which DAE has a protective effect in a rat model of MIA-induced OA.

Paclitaxel-induced peripheral neuropathy (PIPN) is a common and intractable side effect of the conventional chemotherapeutic agent paclitaxel. Acupuncture has been reported as an effective alternative therapy in treatment of PIPN in both basic studies and clinical trials. However, there is a lack of comprehensive surveys to summarize the action of acupuncture in management of PIPN. In this review, we briefly demonstrate the basic pathology of PIPN, which includes the activation of ion channels, mitochondrial dysfunction, disruption of axonal transport and also neuro-inflammatory involvement. Meanwhile, we review both the clinical and basic studies as an emphasis to give a general overview of the therapeutic effect of acupuncture against PIPN. Finally, we summarize the current known mechanisms underlying the action of acupuncture against PIPN mainly at peripheral and spinal levels, which include various neurotransmitters, multiple receptors, different types of enzymes and molecules. In conclusion, acupuncture could be considered as a potential alternative therapy in treatment of PIPN, and further clinical and experimental studies are called for in the future.

Illusions and hallucinations are commonly encountered in both daily life and clinical practice. In this chapter, we review definitions and possible underlying mechanisms of these phenomena and then review what is known about specific conditions that are associated with them, including ophthalmic causes, migraine, epilepsy, Parkinson's disease, and schizophrenia. We then discuss specific syndromes including the Charles Bonnet syndrome, visual snow syndrome, Alice in Wonderland syndrome, and peduncular hallucinosis. The scientific study of illusions and hallucinations has contributed significantly to our understanding of how eye and brain process vision and contribute to perception. Important concepts are the distinction between topologic and hodologic mechanisms underlying hallucinations and the involvement of attentional networks. This chapter examines the various ways in which pathological illusions and hallucinations might arise in relation to the phenomenology and known pathology of the various conditions associated with them.

Intrahepatic cholestasis of pregnancy (ICP) is a common disorder in the second half of pregnancy characterized by pruritus and elevated serum bile acids (BAs) with spontaneous resolution after delivery. ICP carries a risk of adverse effects on the fetus which correlates with the degree of BA elevation. ICP occurs in genetically susceptible women as the reproductive hormones increase during pregnancy. Ursodeoxycholic acid is still considered the first-line treatment for ICP though it is of unproven benefit in preventing adverse effects on the fetus. Fetal complications, such as stillbirth, increase with gestational age, so preterm delivery is generally performed in cases of severe ICP, defined as BA levels above 40 μmol/L. ICP may recur in future pregnancies and is associated with an increased risk for future hepatobiliary, immune mediated, and cardiovascular diseases. Children born of mothers with ICP have normal development but may have a risk for subsequent metabolic disease.

Actinomycosis can be one of the causes of persistent periradicular lesions. This is the report of a patient who was first referred with complaint of pain in maxillary right incisors. A standard root canal therapy was carried out. Unluckily, the patient returned with recurrent symptoms; therefore, surgical endodontic retreatment was decided. While the large periradicular lesion was curetted, a whitish yellow granule-like material came out from the periapical area that was submitted for histopathological examination. The apices of both maxillary right incisors were resected. Root-end cavities were sealed with calcium-enriched mixture (CEM) cement. Finally, the remaining large defect was filled with natural bone substitutes. Since the histopathological diagnosis revealed actinomycotic infection, oral penicillin V was prescribed for four weeks. At two-year recall, the bone healing process was completed. Apical actinomycosis can cause therapy-resistant lesions. Root-end surgery employing CEM and bone substitutes might be an effective method to help bone healing in large periradicular lesions.

The recent data have shown that in addition to biological and psychosocial mechanisms, individual pain perception can be altered by satiety level as well. Some studies confirm that there is a relationship between being fed by sucrose and hyperalgesia in animals, while others show that ketogenic diet can be associated with decreased pain sensitivity to thermal stimuli. It can be argued that the effect of satiety level on pain perception is mediated by gastrointestinal hormones and endogenous opioids. Pharmacological stimulation of kappa-opioid receptors decreases stress and promotes analgesia. Accordingly, these changes can be inhibited by applying antagonists. Our study aims to assess pain perception induced by mechanical experimental irritation in women during different satiety levels in follicular phase of ovarian-menstrual cycle. The sample of the study was comprised of volunteer students aged 18-23 (women, mean age 19,5±2,9). Ovarian-menstrual cycle of the women participating in the research were evaluated using the questionnaires. All the studies were performed in the follicular phase of menstrual cycle (7-11 days of the cycle). At the first stage, study was conducted in starvation state – after 10-12 hours after the last meal, the second stage – in primary, sensory-motor satiety 20-30 minutes after a mixed meal intake. Every participant has been offered a standard, mixed meal (including proteins, fats, carbohydrates). Mechanical pain sensitivity was evaluated using computerized algometer – AlgoMed (Medoc, Ltd, Ramat Yishai, Israel), which was delivering mechanical stimuli to the participants; Meanwhile, mechanical pressure threshold, mechanical pain threshold and pain tolerance threshold were determined. According to this data, the reason of relatively diminished pain perception during primary satiety should be alterations of gastrointestinal tract that take place after food ingestion: Mechano- and chemoreceptors of initial segments in digestive system, particularly in stomach and in duodenum get irritated; that is followed by activation of several humoral factors and duodenal afferentation. In addition, by some authors duodenal release of cholecystokinin is believed to be hypothetical cause of decreased pain sensitivity after 20-30 minutes from the last mixed meal and is thought to have antinociceptive effect on endogenous opioid system.

Cardiovascular drugs are used to treat arterial hypertension, hyperlipidemia, arrhythmias, heart failure, and coronary artery disease. They also include antiplatelet and anticoagulant drugs that are essential for prevention of cardiogenic embolism. Most neurologic complications of the cardiovascular drugs are minor or transient and are far outweighed by the anticipated benefits of treatment. Other neurologic complications are more serious and require early recognition and management. Overtreatment of arterial hypertension may cause lightheadedness or fatigue but often responds readily to dose adjustment or an alternative drug. Other drug complications may be more troublesome as in myalgia associated with statins or headache associated with vasodilators. The recognized bleeding risk of the antithrombotics requires careful calculation of risk/benefit ratios for individual patients. Many neurologic complications of cardiovascular drugs are well documented in clinical trials with known frequency and severity, but others are rare and recognized only in isolated case reports or small case series. This chapter draws on both sources to report the adverse effects on muscle, nerve, and brain associated with commonly used cardiovascular drugs.

Inhalational anesthesia and propofol-based total intravenous anesthesia (TIVA) are the two most popular methods of general anesthesia with distinct characteristics that may affect quality of recovery (QOR) differently. This study compared QOR after corrective lower limb osteotomy between desflurane-based inhalational anesthesia and propofol-based TIVA.