Rejected

Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain based on tooth pulp stimulation. More specifically, we assessed the effects of intracerbroventricular (i.c.v.) and intraperitoneal (i.p.) administration of URB597 on the amplitude of evoked tongue jerks (ETJ) in rats. The levels of the investigated mediators anandamide (AEA), 2-arachidonyl glycerol (2-AG), Substance P (SP), calcitonin-gene-related peptide (CGRP), endomorphin-2 (EM-2) and fatty acid amide hydrolase (FAAH) inhibitor by URB597 and receptors cannabinoid type-1 receptors (CB1R), cannabinoid type-2 receptors (CB2R) and µ-opioid receptors (MOR) were determined in the mesencephalon, thalamus and hypothalamus tissues. We have shown that increasing endocannabinoid AEA levels by both central and peripheral inhibition of FAAH inhibitor by URB597 has an antinociceptive effect on the trigemino-hypoglossal reflex mediated by CB1R and influences the activation of the brain areas studied. On the other hand, URB597 had no effect on the concentration of 2-AG in the examined brain structures and caused a significant decrease in CB2R mRNA expression in the hypothalamus only. Tooth pulp stimulation caused in a significant increase in SP, CGRP and EM-2 gene expression in the midbrain, thalamus and hypothalamus. In contrast, URB597 administered peripherally one hour before stimulation decreased the mRNA level of these endogenous neuropeptides in comparison with the control and stimulation in all examined brain structures. Our results show that centrally and peripherally administered URB597 is effective at preventing orofacial pain by inhibiting AEA catabolism and reducing the level of CGRP, SP and EM-2 gene expression and that AEA and 2-AG have different species and model-specific regulatory mechanisms. The data presented in this study may represent a new promising therapeutic target in the treatment of orofacial pain.

The aims of this article were to describe 2 patients with a pathological diagnosis of differentiated exophytic vulvar intraepithelial lesion and to summarize the literature regarding this relatively new diagnosis.

The effectiveness and safety of memantine for headache are elusive, and this meta-analysis aimed to explore the influence of memantine versus placebo for headache.

Lumbar disc herniation (LDH) is a common chronic musculoskeletal disorder that seriously affects quality of life. The percutaneous endoscopic lumbar diskectomy (PELD) technique was developed to address spinal nerve root compression through direct visualization of pathological findings while minimizing tissue destruction upon exposure. It is an effective and safe treatment for LDH. However, recurrent LDH is a major concern after lumbar discectomy for primary LDH. A considerable number of clinical studies have reported that patients with LDH with radiculopathy could benefit from manual therapy. Shi's manual therapy (SMT) was established based on traditional Chinese medicine (TCM) theory and has been shown to have a superior effect in alleviating muscle tension and loosening joints to improve lumbar and leg pain, radiculopathy, stiffness, activity discomfort, and related disorders. However, there is a lack of high-quality clinical evidence to support this conclusion. The purpose of this study is to evaluate the efficacy and safety of the combination of Shi's manual therapy (SMT) and PELD for LDH with radiculopathy.

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference -3.8 mg, 95% CI -10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI -2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

Continuous peripheral nerve block, also known as "local anesthetic perineural infusion," refers to percutaneous placement of a catheter near a peripheral nerve or plexus followed by administration of a local anesthetic through a catheter to provide anesthesia, or analgesia for several days, in some cases even for a month. This report describes the case of a 7 year old boy with left elbow contracture with limited flexion and extension who was admitted to the Clinic of Pediatric Surgery for redressment of the elbow and physical therapy. An ultrasound-guided axillary brachial plexus block was performed, with placement of a non-tunneled perineural catheter. Redressment of the left elbow was performed twice and before each redressment boluses of local anesthetic were applied through the perineural catheter. Physical therapy was performed painlessly with continuous perineural infusion. On the 5th day of catheter placement, the perineural catheter was removed without any prior complications such as hematoma, infection, catheter dislocation or leakage of local anesthetic. Our goal is to minimize the psychological and physical trauma to the patient, no matter how immature the patient is. Continuous regional anesthesia in children is a safe technique in postoperative pain management that facilitates early mobilization due to its sufficient analgesia and better comfort. It can provide in-home treatment, with adequate education for patients and parents, and improve rehabilitation in children.

Transcranial Doppler (TCD) is an easy, non-invasive, and real-time monitoring device for detecting right-to-left shunts (RLS). Nonetheless, it has limited benefits in patients with poor temporal windows. Therefore, we aimed to investigate whether the basilar artery (BA) window was as effective as the middle cerebral artery (MCA) in detecting RLS during TCD monitoring. Overall, we enrolled 344 patients with stroke, transient ischemic attack, headache, or dizziness. MCA and BA were monitored using a modified headset. To investigate the feasibility of the suboccipital window in detecting RLS, we instituted an evaluation tool with three tiers to evaluate microembolic signals (MESs) during TCD monitoring. Tier 1: TCD monitoring of the MCA (bilaterally) in the resting state, tier 2: TCD monitoring of the MCA (bilaterally) while performing the Valsalva maneuver, and tier 3: TCD monitoring of the index MCA and BA while performing the Valsalva maneuver. In tiers 2 and 3, a high agreement rate of 0.808 and 0.809 (p < 0.001), respectively, on the weighted kappa index, and a high intra-class correlation coefficient of 0.982 and 0.986 (p < 0.001), respectively, were observed on detecting MESs. Our data suggests that the BA window is as effective as the MCA window for detecting RLS on TCD.

Median arcuate ligament syndrome (MALS) is a rare condition that is often overlooked as a result of its nonspecific symptoms. It is usually presented with nausea, bloating, abdominal postprandial pain, and weight loss. The diagnosis of MALS is usually delayed and made by excluding other causes for the symptoms. The diagnosis of this syndrome is based on clinical presentation and radiological findings on computer tomography angiography (CTA) or magnetic resonance angiography (MRA). Surgery is treatment of choice, with promising results from laparoscopic surgery.

A man in his 60s presented with a worsening headache, confusion and expressive dysphasia which, on admission, progressed to a falling Glasgow Coma Score and seizures. He was subsequently admitted to the intensive care unit. The clinical diagnosis was antibody-negative autoimmune encephalitis. Despite immunotherapy, the patient died 5 months after initial presentation and postmortem examination revealed he had CD8 encephalitis. This case demonstrates that CD8 encephalitis can present similarly to autoimmune encephalitis both clinically and on imaging. A brain biopsy would have revealed the diagnosis in life, although this would not have altered his treatment.

Real-world data in patients with moderate psoriasis treated with apremilast is limited.