(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders

The discovery of the endocannabinoidome (eCBome) is evolving gradually with yet to be elucidated functional lipid mediators and receptors. The diet modulates these bioactive lipids and the gut microbiome, both working in an entwined alliance. Mounting evidence suggests that, in different ways and with a certain specialisation, lipid signalling mediators such as N-acylethanolamines (NAEs), 2-monoacylglycerols (2-MAGs), and N-acyl-amino acids (NAAs), along with endocannabinoids (eCBs), can modulate physiological mechanisms underpinning appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition, and immunity. This knowledge has been primarily utilised in pharmacology and medicine to develop many drugs targeting the fine and specific molecular pathways orchestrating eCB and eCBome activity. Conversely, the contribution of dietary NAEs, 2-MAGs and eCBs to the biological functions of these molecules has been little studied. In this review, we discuss the importance of (Wh) olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N) utrition (WHEN), in the management of obesity and related disorders.

Case Series of Irritated Giant Acrochordons Arising from Skin Folds

BACKGROUND: Acrochordons are pedunculated papules or nodules with a soft consistency and smooth contour, sometimes apparently growths often hang on thin stalk, with the most acrochordons size was 2–5 mm. Occasionally, due to frictions of the pedicle, acrochordon can become inflamed, tender, and even gangrenous. CASE PRESENTATION: We report a case series of three giant acrochordons, first case, 19-year-old female come to my OPD clinic with a big mass on her left vagina, with pain and hot while being touched, and fever. On examination big nodule on the right labia mayor was found, with diameter 20 × 20 cm, short stalk, firm, warmed, and pain sensation while touched, with several excoriated skin surface. Second case, 23-year-old female presented in my OPD with a mass in her left vagina, associated with pain and several bleeding spots while being touched, with diameter of 5 × 5 cm. Third case, 31-year-old female consulted to OPD clinic with a year of history having a mass on her right buttock, which gradually increases in size and causing a light pain. On examination, short pedunculated nodule was found at the right buttock, diameter 10 × 6 cm, oval shape, firm, and several excoriated plaques. All cases were diagnosed as giant acrochordons and were performed excision. The previous studies state that the larger lesions of acrochordons in the groin or upper thighs maybe associated with diabetes mellitus and obese individuals. Due to the twisting or strangulated of the pedicle, all three cases of giant acrochordons become inflamed, tender, irritated, infarction, and even gangrenous. In general, it was advised to have the acrochordons removed, particularly in the skin fold of axillae, groin, or vagina, since they will gradually develop in size. CONCLUSION: Giant acrochordons usually relate to the growth hormone like activity. Hence, they may associate with endocrine disorder. It may occasionally become inflamed, tender, and even gangrenous due to frictions. General principle is to have the acrochordons removed, particularly in skin fold area.

Trans Vaginal Versus Trans Abdominal Ultrasound Guided Embryo Transfer in In vitro Fertilization and Intra Cytoplasmic Sperm Injection (IVF–ICSI)

Background: Embryo transfer (ET) refers to a step in the process of assisted reproduction in which one or several embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique, which is often used in connection with in vitro fertilization (IVF), has widely been used in animals or human. The aim of this study was to compare Trans abdominal ultrasound (TAUS) with Trans vaginal ultrasound (TVUS) methods for guidance of (ET) regarding clinical pregnancy rate and patient appreciation of pain during embryo transfer. Methods: This prospective, randomized, controlled study was conducted on 100 patients undergoing cryopreserved or fresh morula or blastocyte who were randomized (computer generated program) into 2 groups. Group I (the study group): 50 patients were subjected to embryo transfer under trans abdominal ultrasound guidance and Group II (controlled group): 50 patients were subjected to (ET) under (TAUS). Results: There were no statistically significant differences regarding fresh and cryopreserved. TVUS group demonstrated significant reduction of duration compared to TAUS ones. Minimal pain was observed in TVUS cases compared to TAUS ones. Higher success rate and lower failure rate were demonstrated in TVUS group compared to TAUS group. Conclusions: TVUS seems to have higher success rate with less pain sensation as well as shorter duration of the procedure in comparison with TAUS.

Understanding the Mechanism of Action of NAI-112, a Lanthipeptide with Potent Antinociceptive Activity

NAI-112, a glycosylated, labionine-containing lanthipeptide with weak antibacterial activity, has demonstrated analgesic activity in relevant mouse models of nociceptive and neuropathic pain. However, the mechanism(s) through which NAI-112 exerts its analgesic and antibacterial activities is not known. In this study, we analyzed changes in the spinal cord lipidome resulting from treatment with NAI-112 of naive and in-pain mice. Notably, NAI-112 led to an increase in phosphatidic acid levels in both no-pain and pain models and to a decrease in lysophosphatidic acid levels in the pain model only. We also showed that NAI-112 can form complexes with dipalmitoyl-phosphatidic acid and that Staphylococcus aureus can become resistant to NAI-112 through serial passages at sub-inhibitory concentrations of the compound. The resulting resistant mutants were phenotypically and genotypically related to vancomycin-insensitive S. aureus strains, suggesting that NAI-112 binds to the peptidoglycan intermediate lipid II. Altogether, our results suggest that NAI-112 binds to phosphate-containing lipids and blocks pain sensation by decreasing levels of lysophosphatidic acid in the TRPV1 pathway.

Amplified Vasodilatation within the Referred Pain Zone of Trigger Points Is Characteristic of Gluteal Syndrome—A Type of Nociplastic Pain Mimicking Sciatica

Gluteal syndrome (GS) mimicking sciatica is a new disease that has been recently recognized and included in the International Classification of Diseases, 11th Revision. The present study examines nociplastic pain involvement in GS and sciatica patients using a new Skorupska protocol (SP) test that provokes amplified vasodilatation in the area of expected muscle-referred pain. A positive test is confirmed if there is (i) a development of autonomic referred pain (AURP) and (ii) an increase in the delta of average temperature (Δ₸°) > 0.3 °C at the end of the stimulation and during the observation SP phases. Chronic GS (n = 20) and sciatica (n = 30) patients were examined. The SP test confirmed muscle-referred pain for (i) all GS patients with 90.6% positive thermograms (Δ₸° 0.6 ± 0.8 °C; maximum AURP 8.9 ± 13.6% (both p < 0.05)) and (ii) those sciatica (n = 8) patients who reported pain sensation during the test with 20.6% positive thermograms (Δ₸° 0.7 ± 0.7 °C; maximum AURP 15.1 ± 17.8% (both p < 0.05)). The remaining sciatica (n = 22) patients did not report pain during the test and presented a Δ₸° decrease and the AURP size below 1%. Conclusion: Amplified vasodilatation suggesting nociplastic pain involvement was confirmed for all GS and sciatica patients who reported painful sensations in the zone typical for gluteus minimus referred pain during the test.

Chronic Pain – What is it?

The brain stem and brain are involved in chronic pain processing and sensation. This may involve changes in gene expression through epigenetic alterations [1]. Chronic pain is also a learned experience which involves the brain [2]. In chronic pain, thresholds to pain sensation decrease such that pain may be produced by nonpainful stimuli.

Assessment of post-operative analgesia in modified radical mastectomy patients using surgical wound irrigation with 0.25% bupivacaine

Modified Radical Mastectomy is the widely followed treatment for operable breast cancers. Among the methods used to alleviate pain, irrigation of wound with 0.25% Bupivacaine is one of the under-utilized methods with good efficiency compared to other drugs.To evaluate the role of local irrigation of 0.25% bupivacaine in alleviating the post-operative pain. This observational study was conducted among 60 female patients who underwent Modified Radical Mastectomy in a tertiary care teaching hospital between January 2017 and July 2018. Thirty (30) patients were randomly allotted to control group, where the routine post-operative pain management was followed. Another 30 were randomly allotted to study group where, before closure of the wound, a 20G scalp vein set was used along the length of the incision with multiple punctures in it for continuous irrigation with 0.25% Bupivacaine. Post operatively Visual analogue scale was used to measure the pain sensation at every six hours for 24 hours. The adverse effects like pain, hematoma, wound dehiscence, infection was noted on all the post-operative days.Both the groups were similar with respect to basic parameters measured. There was a significant reduction in need for rescue analgesia in the study group. There was a significant difference in mean VAS score between both groups from 6 hour of surgery. Post-operative nausea and vomiting was significantly less in the study group. Irrigation of wound with 0.25% Bupivacaine is found to reduce the pain sensation with minimal side effects without systemic compromise.

Pathomechanisms of Paclitaxel-Induced Peripheral Neuropathy

Peripheral neuropathy is one of the most common side effects of chemotherapy, affecting up to 60% of all cancer patients receiving chemotherapy. Moreover, paclitaxel induces neuropathy in up to 97% of all gynecological and urological cancer patients. In cancer cells, paclitaxel induces cell death via microtubule stabilization interrupting cell mitosis. However, paclitaxel also affects cells of the central and peripheral nervous system. The main symptoms are pain and numbness in hands and feet due to paclitaxel accumulation in the dorsal root ganglia. This review describes in detail the pathomechanisms of paclitaxel in the peripheral nervous system. Symptoms occur due to a length-dependent axonal sensory neuropathy, where axons are symmetrically damaged and die back. Due to microtubule stabilization, axonal transport is disrupted, leading to ATP undersupply and oxidative stress. Moreover, mitochondria morphology is altered during paclitaxel treatment. A key player in pain sensation and axonal damage is the paclitaxel-induced inflammation in the spinal cord as well as the dorsal root ganglia. An increased expression of chemokines and cytokines such as IL-1β, IL-8, and TNF-α, but also CXCR4, RAGE, CXCL1, CXCL12, CX3CL1, and C3 promote glial activation and accumulation, and pain sensation. These findings are further elucidated in this review.