Rejected

Neuropathic pain is an intractable chronic pain condition that is mainly caused by allodynia. We had previously reported that intra-plantar administration of bergamot essential oil (BEO) containing an aromatic compound significantly suppressed partial sciatic nerve ligation (PSNL)-induced mechanical allodynia opioid mu receptors in mice. However, it has also been reported that the inhalation of BEO reduced formalin-induced nociceptive responses. Therefore, we aimed to elucidate whether the analgesic action of BEO is mediated by olfactory stimulation through volatile components. In the current study, BEO was continuously administered with an osmotic pump during PSNL surgery, and the effects on mice behavior were examined pharmacologically using a double activity monitoring system, which can detect two-dimensional planar motion in a cage with an infrared beam sensor as well as active motion with a running wheel. Here, we report that the two-dimensional planar activity significantly increased in mice with PSNL in the light phase (from 8 o'clock to 20 o'clock) but not in the dark phase (from 20 o'clock to 8 o'clock) from the second day after surgery. However, this increase was not observed when BEO was continuously administered. The effect of BEO on the two-dimensional planar counts in mice with PSNL was antagonized by naloxone hydrochloride. Regarding the running wheel activity, the number of rotations decreased by PSNL in the dark phase from the 8th day after surgery. However, this was not apparent with BEO use. The effect of BEO on the number of rotations was also antagonized by naloxone hydrochloride. Furthermore, inhalation of BEO in PSNL mice did not affect mechanical allodynia or the two-dimensional planar motion or running wheel activities. These findings indicate that BEO exhibits an analgesic action, which is mediated by opioid receptors and not by the olfactory system.

The incidence of moderate to severe pain is high among patients undergoing spinal surgery. Nefopam can be used as an adjuvant analgesic postoperatively after spine surgery. The study aimed to assess the analgesic efficacy and side effects of nefopam on 24-hour postoperative morphine consumption after spine surgery. The study is a randomized, double-blinded, placebo-controlled trial. A total of 96 patients were randomized into 4 treatment groups, 24 each. In group 1, patients received normal saline before surgical incision and before the end of surgery. In group 2, patients received 30 mg nefopam before surgical incision and normal saline before the end of surgery. In group 3, patients received normal saline before surgical incision and 30 mg of nefopam before the end of surgery. In group 4, patients received 30 mg of nefopam in both timings. Patient-controlled analgesia morphine was used for the postoperative period. Outcomes were to determine 24-hour morphine consumption and incidence of side effects.   Of 96 patients enrolled, 21 in placebo-placebo, 22 in nefopam-placebo, 22 in placebo-nefopam and 21 in nefopam-nefopam groups completed the study. Analysis of the Kruskal-Wallis test shows no significant difference in 24-hour postoperative morphine consumption between four groups, which were 18 [IQR 13.5-29], 20 [IQR 11-28.3], 17 [IQR 11.5-28.5], 13 [IQR 8.5-18.5] mg., respectively (p = 0.223).  Incidence of side effects, including tachycardia, sedation, sweating and nausea/ vomiting, did not differ. Adding perioperative nefopam to opioid analgesic does not improve analgesic efficacy in patients who underwent spine surgery. Thai Clinical Trials Registry ID TCTR20171115001; registered on 15 November 2017.

Osteoid osteoma (OO) is a benign bone tumor that usually presents between 10 and 35 years of age. The metaphysis and diaphysis of the femur and tibia are the typical locations. The diagnosis is usually straightforward when images reveal a radiolucent nidus surrounded by reactive sclerosis. However, the diagnosis is more difficult when it occurs at atypical locations with nonspecific and misleading appearance on images. OO may mimic juvenile idiopathic arthritis (JIA), bone infection, or malignancy. We present a 14-year-old male with a 4-month history of left hip pain. His pain was worse with playing hockey and lacrosse and in the morning and sometimes woke him up at night. His examination was significant for pain with flexion and external rotation of the left hip and for mild limitation of full external rotation. Blood work revealed normal complete blood count, erythrocyte sedimentation rate, and C-reactive protein. Left hip X-ray was unremarkable. Left hip MR arthrogram showed marked edema of the medial and posterior walls of the left acetabulum. CT-guided biopsy of the left acetabulum showed unremarkable flow cytometry and chronic inflammatory component raising concern about chronic recurrent multifocal osteomyelitis (CRMO). Bone scan revealed focal increased uptake in the left acetabulum and no additional abnormality. Repeat MRI with intravenous contrast showed a left hip effusion, focal synovial enhancement in the medial left hip, and acetabula edema. The patient failed treatment for presumed JIA and CRMO with nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, methotrexate, and adalimumab. CT scan of the left hip was performed for further evaluation of the bone and showed 11 × 6 mm low attenuation focus with subtle internal nidus in the posteromedial aspect of the acetabular rim, suggestive of intra-articular OO. Radiofrequency ablation was performed with no complications, and the left hip pain improved. The atypical location resulted in delay of diagnosis for 12 months after presentation. We highlight the diagnostic pitfalls observed in atypical OO locations and the difficulties this creates with making the diagnosis. OO mimicking JIA has previously been described. We submit CRMO as another differential diagnosis which may be mimicked and demonstrate the vital role of CT scan in the diagnosis.

To develop a self-administered diagnostic screening questionnaire for lumbar spinal stenosis (LSS) consisting of items with high content validity and to investigate the diagnostic value of the questionnaire and the items.

Choosing an appropriate treatment for chronic pain remains problematic, and despite the available medication for its treatment, still, many patients complain about pain and appeal to the use of cannabis derivatives for pain control. However, few data have been provided to clinicians about the pharmacokinetic drug-drug interactions of cannabinoids with other concomitant administered medications. Therefore, the aim of this brief review is to assess the interactions between cannabinoids and pain medication through drug transporters (ATP-binding cassette superfamily members) and/or metabolizing enzymes (cytochromes P450 and glucuronyl transferases).

Transient receptor potential (TRP) are cation channels expressed in both non-excitable and excitable cells from diverse tissues, including heart, lung, and brain. The TRP channel family includes 28 isoforms activated by physical and chemical stimuli, such as temperature, pH, osmotic pressure, and noxious stimuli. Recently, it has been shown that TRP channels are also directly or indirectly activated by reactive oxygen species. Oxidative stress plays an essential role in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, and TRP channels are involved in the progression of those diseases by mechanisms involving changes in the crosstalk between Ca regulation, oxidative stress, and production of inflammatory mediators. TRP channels involved in nociception include members of the TRPV, TRPM, TRPA, and TRPC subfamilies that transduce physical and chemical noxious stimuli. It has also been reported that pain is a complex issue in patients with Alzheimer's and Parkinson's diseases, and adequate management of pain in those conditions is still in discussion. TRPV1 has a role in neuroinflammation, a critical mechanism involved in neurodegeneration. Therefore, some studies have considered TRPV1 as a target for both pain treatment and neurodegenerative disorders. Thus, this review aimed to describe the TRP-dependent mechanism that can mediate pain sensation in neurodegenerative diseases and the therapeutic approach available to palliate pain and neurodegenerative symptoms throughout the regulation of these channels.

Pituitary metastases (PM) are rare events and to date only very few cases of melanoma PM have been described in literature up to now. We describe the clinical history of a 33-year-old male patient who underwent surgical excision of an inter-scapular melanoma in 2008. The subsequent follow-up was negative for ~10 years. In September 2018, due to the onset of a severe headache, the patient underwent a brain magnetic resonance imaging, which showed an expansive mass in the saddle and suprasellar region with a maximum diameter of 17 mm. Pituitary function tests and visual field were normal. Worsening of the headache and the appearance of a left eye ptosis led the patient to surgical removal of the lesion in October 2018. The histological examination unexpectedly showed metastasis of the melanoma. Post-operative hormonal assessment showed secondary hypothyroidism and hypoadrenalism, which were both promptly treated, and a mild hypogonadism. Three months after surgery, a sellar MRI showed a persistent, increased pituitary mass (3 cm of diameter); fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) detected an increased radiopharmaceutical uptake in the sellar region. Due to the persistence of the disease and the evidence of a BRAF V600E mutation, in February 2019, the patient underwent a combined treatment with dabrafenib (a BRAF inhibitor) and trametinib (mitogen-activated extracellular signal-regulate kinase inhibitor). Sellar MRI performed 6 months later showed no evidence of mass in the sellar region. The patient was in a good clinical condition and did not complain of headaches or other symptoms; there were no significant side-effects from the anticancer therapy. After 13 months of treatment, the patient showed no recurrence of the disease on morphological imaging. Anticancer therapy was confirmed, replacement therapies with hydrocortisone and levothyroxine continued and the pituitary-gonadal axis was restored. This is a very interesting case, both for the rarity of the pituitary melanoma metastasis and for the singular therapeutic course carried out by the patient. This is the first case of a pituitary melanoma metastasis with BRAF mutation, successfully treated with the combination of dabrafenib and trametinib after incomplete surgical removal.

How has the storage of information shaped human cognition? We bring together current advances in cognitive science, the neurobiology of memory, and archeology to explore how storage of information affects consciousness. These fields strongly suggest that the increase in storage of information in the environment – which we call exosomatic storage of information – may have led to changes in human consciousness and human neurophysiology over time. To bring these findings together conceptually, we develop what we call a dialectical model of the relationship between storage of information and the development of human consciousness. Using the system of dialectic philosophy, we put forward that (a) environmental changes, consciousness, and neurophysiology develop together, (b) these changes were irreversible, (c) quantitative increases in exosomatic storage of information may have led to qualitative changes in human consciousness and neurophysiology, (d) these changes in turn affected how we see ourselves. Indeed, our capacity to store information exosomatically distinguishes us from other animals, and may be a key attribute of our self-awareness and therefore self-consciousness. Because metaphors are central to human thought and can help structure scientific inquiry, we illustrate our model using a metaphor of drops of silver on the back of a glass, eventually making a mirror – where successive quantitative change leads to an irreversible qualitative development in human consciousness. The dialectic model can offer new insights into the co-evolution of material culture and human beings through its broader philosophical foundations and explanatory power.

The risk factors, disease characteristics, severity, and mortality of COVID-19 are unclear, particularly in Egypt.

The aim: to compare the efficacy of pectoral nerve block type II and thoracic paravertebral block for analgesia during and after breast cancer surgery.