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Turkish Journal of Medical Sciences 2023Neuropathic pain (NP) is a type of chronic pain usually caused by damage to the somatosensory system. Bioactive antioxidant compounds, such as curcumin and ginger, are...
BACKGROUND/AIM
Neuropathic pain (NP) is a type of chronic pain usually caused by damage to the somatosensory system. Bioactive antioxidant compounds, such as curcumin and ginger, are widely preferred in the treatment of NP. However, the ingredient-based mechanism that underlies their pain-relieving activity remains unknown. The aim of this study was to investigate the therapeutic effects of trans-[6]-Shogaol and [6]-Gingerol active ingredients of the Roscoe extract on the spinal cord and cortex in the neuroinflammatory pathway in rats with experimental sciatic nerve injury.
MATERIALS AND METHODS
Forty-six volatile phenolic components were identified in ginger samples using gas chromatography-mass spectrometry analysis. Thirty 3-month-old male 250-300 g Wistar Albino rats were divided into three groups as (i) sham, (ii) chronic constriction injury (CCI), and (iii) CCI+ginger. NP was induced using the CCI model. A ginger extract treatment enriched with trans-[6]-shogaol and [6]-gingerol active ingredients was administered by gavage at 200 mg/kg/day for 7 days. On the 14th day of the experiment, locomotor activity was evaluated in open field and hyperalgesia in tail flick tests.
RESULTS
In behavioural experiments, a significant decrease was observed in the CCI group compared to the sham group, while a significant increase was observed in the CCI+ginger group compared to the CCI group (p < 0.05). In the spinal cord and cortex tissues, there was a significant increase in the TNF-α, IL-1β, and IL-18 neuroinflammation results of the CCI group compared to the sham group, while there was a significant decrease in the CCI+ginger group compared to the CCI group.
CONCLUSION
In this study, ginger treatment was shown to have a therapeutic effect on neuroinflammation against sciatic nerve damage.
Topics: Animals; Fatty Alcohols; Catechols; Neuralgia; Rats; Male; Rats, Wistar; Zingiber officinale; Disease Models, Animal; Cytokines; Plant Extracts; Sciatic Nerve; Spinal Cord
PubMed: 38813490
DOI: 10.55730/1300-0144.5728 -
Brain, Behavior, & Immunity - Health Jul 2024The nerve growth factor receptor, also referred to as tumour necrosis factor II and the p75 neurotrophin receptor (p75), serves pleiotropic functions in both the...
The nerve growth factor receptor, also referred to as tumour necrosis factor II and the p75 neurotrophin receptor (p75), serves pleiotropic functions in both the peripheral and central nervous system, involving modulation of immune responses, cell survival and cell death signalling in response to multiple ligands including cytokines such as TNFα, as well as proneurotrophins and mature neurotrophins. Whilst and studies have characterised various responses of the p75 receptor in isolated conditions, it remains unclear whether the p75 receptor serves to provide neuroprotection or contributes to neurotoxicity in neuroinflammatory and neurotrophin-deficit conditions, such as those presenting in schizophrenia. The purpose of this mini-review is to characterise the potential signalling mechanisms of the p75 receptor respective to neuropathological changes prevailing in schizophrenia to ultimately propose how specific functions of the receptor may underlie altered levels of p75 in specific cell types. On the basis of this evaluation, this mini-review aims to promote avenues for future research in utilising the therapeutic potential of ligands for the p75 receptor in psychiatric disorders, whereby heightened inflammation and reductions in trophic signalling mechanisms coalesce in the brain, potentially resulting in tissue damage.
PubMed: 38813083
DOI: 10.1016/j.bbih.2024.100796 -
Turkish Journal of Medical Sciences 2023Dorsal root ganglia (DRG) are structures containing primary sensory neurons. Intraganglionic (IG) and intrathecal (IT) applications are the most common methods used for... (Comparative Study)
Comparative Study
BACKGROUND/AIM
Dorsal root ganglia (DRG) are structures containing primary sensory neurons. Intraganglionic (IG) and intrathecal (IT) applications are the most common methods used for viral vector transfer to DRG. We aim to compare the efficiencies and pathological effects of IT and IG viral vector delivery methods to DRG, through in vivo imaging.
MATERIALS AND METHODS
Mice were divided into four groups of six each: IT, IG, IT-vehicle, and IG-vehicle. Adeno-associated virus (AAV) injection was performed for EGFP expression in IT/IG groups. DRGs were made visible through vertebral window surgery and visualized with multiphoton microscopy. After imaging, spinal cords and DRGs were removed and cleared, then imaged with light sheet microscopy.
RESULTS
No neuronal death was observed after IT injection, while the death rate was 17% 24 h after IG injection. EGFP expression efficiencies were 90%-95% of neurons in both groups. EGFP expression was only observed in targeted L2 DRG after IG injection, while it was observed in DRGs located between L1-L5 levels after IT injection.
CONCLUSION
IT injection is a more suitable method for labeling DRG neurons in neurodegenerative injury models. However, when the innervation of DRG needs to be specifically studied, IT injection reduces this specificity due to its spread. In these studies, IG injection is the most suitable method for labeling single DRG neurons.
Topics: Animals; Ganglia, Spinal; Injections, Spinal; Mice; Dependovirus; Green Fluorescent Proteins; Genetic Vectors; Male
PubMed: 38813001
DOI: 10.55730/1300-0144.5702 -
Frontiers in Oncology 2024Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs),...
BACKGROUND
Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs.
METHODS
Through confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested.
RESULTS
Through confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational super-resolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure.
CONCLUSION
We provide first evidence of the ANS as the principal non-tumor target of anti-GD2 mAbs in humans. We describe the development and modeling of the Step-Up protocol exploiting the tachyphylaxis phenomenon we demonstrate in patients using the SSR test.
PubMed: 38812778
DOI: 10.3389/fonc.2024.1380917 -
Turkish Journal of Medical Sciences 2024In this study, it was aimed to retrospectively compare the effect of greater occipital nerve (GON) block performed with ultrasonography using low (0.3%) and high (0.5%)... (Comparative Study)
Comparative Study
BACKGROUND/AIM
In this study, it was aimed to retrospectively compare the effect of greater occipital nerve (GON) block performed with ultrasonography using low (0.3%) and high (0.5%) concentrations of bupivacaine on pain scores and patient satisfaction in chronic migraine (CM).
MATERIALS AND METHODS
The mean number of days with pain, the mean duration of pain in the attacks, and the highest numerical rating scale (NRS) scores recorded in the 1 month preblock and 1 and 3 months postblock of 80 patients (40 for Group 1, 0.3% bupivacaine; 40 for Group 2, 0.5% bupivacaine) who underwent ultrasonography-guided GON block were recorded from the patient file data. According to the protocol applied by our clinic, GON block was applied to each patient 6 times with the same procedures, in total.
RESULTS
While there was a statistically significant difference between the groups in terms of the number of days with pain and the maximum NRS score in the 1-month preblock evaluation (p = 0.01, p < 0.001), at 3 months postblock, no statistical difference was observed in terms of the number of days with pain, duration of pain, or NRS score (p = 0.961, p = 0.108, and p = 0.567). In the intragroup evaluations, at 3 months postblock, the number of days with pain decreased from 17.5 days to 7 days in Group 1 and from 24.0 days to 8.0 days in Group 2. The duration of pain and maximum NRS values were statistically significantly decreased in the intragroup evaluation in both groups pre and postblock.
CONCLUSION
Complications arising from the procedure and the local anesthetic used are essential points to consider in applying GON block. In CM treatment using GON block application, a similar effect to the standard local anesthetic application (0.5%) can be achieved by administering local anesthetic at a lower dose (0.3%).
Topics: Humans; Bupivacaine; Female; Migraine Disorders; Male; Adult; Nerve Block; Anesthetics, Local; Retrospective Studies; Ultrasonography, Interventional; Middle Aged; Treatment Outcome; Pain Measurement; Chronic Disease; Patient Satisfaction
PubMed: 38812648
DOI: 10.55730/1300-0144.5782 -
Acta Neuropathologica Communications May 2024Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the...
Neurons pose a particular challenge to degradative processes like autophagy due to their long and thin processes. Autophagic vesicles (AVs) are formed at the tip of the axon and transported back to the soma. This transport is essential since the final degradation of the vesicular content occurs only close to or in the soma. Here, we established an in vivo live-imaging model in the rat optic nerve using viral vector mediated LC3-labeling and two-photon-microscopy to analyze axonal transport of AVs. Under basal conditions in vivo, 50% of the AVs are moving with a majority of 85% being transported in the retrograde direction. Transport velocity is higher in the retrograde than in the anterograde direction. A crush lesion of the optic nerve results in a rapid breakdown of retrograde axonal transport while the anterograde transport stays intact over several hours. Close to the lesion site, the formation of AVs is upregulated within the first 6 h after crush, but the clearance of AVs and the levels of lysosomal markers in the adjacent axon are reduced. Expression of p150Glued, an adaptor protein of dynein, is significantly reduced after crush lesion. In vitro, fusion and colocalization of the lysosomal marker cathepsin D with AVs are reduced after axotomy. Taken together, we present here the first in vivo analysis of axonal AV transport in the mammalian CNS using live-imaging. We find that axotomy leads to severe defects of retrograde motility and a decreased clearance of AVs via the lysosomal system.
Topics: Animals; Axonal Transport; Optic Nerve; Rats; Autophagy; Optic Nerve Injuries; Male; Axons; Nerve Degeneration; Rats, Sprague-Dawley; Female
PubMed: 38812004
DOI: 10.1186/s40478-024-01791-2 -
Scientific Reports May 2024Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition...
Despite treatment with levothyroxine, hypothyroidism and autoimmune thyroiditis (AIT) may be associated with reduced quality of life (QoL), an enigmatic condition referred to as "syndrome T". Peripheral neuropathy, described in untreated thyroid disease, could be a contributing mechanism. We analysed autonomic and somatosensory function in 29 patients with AIT and treated hypothyroidism and 27 healthy volunteers. They underwent heart rate variability (HRV) analysis and quantitative sensory testing (n = 28), comprising 13 parameters of small and large nerve fibre function and pain thresholds. Autonomic cardiovascular function was assessed in rest, deep respiration and orthostasis. Additionally, biomarkers for autoimmunity and thyroid function were measured. Anxiety, depression and QoL were assessed using validated questionnaires. 36% of the patients showed at least one sign of somatosensory small or large fibre dysfunction. 57% presented with mild hyperalgesia to at least one stimulus. Several markers of autonomic function and some detection thresholds were related to the antibody titres. Anxiety, depression scores and QoL correlated to antibody titres and HRV measures. Autonomic and somatosensory dysfunction indicate that in treated hypothyroidism and AIT a subgroup of patients suffers from neuropathic symptoms leading to impaired QoL. Additionally, mild hyperalgesia as a possible sensitisation phenomenon should be considered a target for symptomatic treatment.
Topics: Humans; Female; Male; Middle Aged; Adult; Autonomic Nervous System; Quality of Life; Thyroiditis, Autoimmune; Heart Rate; Hypothyroidism; Thyroxine; Aged; Somatosensory Disorders; Anxiety
PubMed: 38811750
DOI: 10.1038/s41598-024-63158-w -
BMC Ophthalmology May 2024We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia...
BACKGROUND
We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) with central nervous system (CNS) involvement.
CASE PRESENTATION
A 65-year-old Asian female with Ph-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased.
CONCLUSIONS
To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.
Topics: Humans; Female; Aged; Leukemic Infiltration; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Optic Nerve; Retinal Diseases; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Visual Acuity
PubMed: 38807037
DOI: 10.1186/s12886-024-03486-7 -
Pain Physician May 2024Radiofrequency thermocoagulation (RFT) of the thoracic nerve root is commonly employed in treating medication-refractory thoracic post-herpetic neuralgia (PHN). However,... (Comparative Study)
Comparative Study
BACKGROUND
Radiofrequency thermocoagulation (RFT) of the thoracic nerve root is commonly employed in treating medication-refractory thoracic post-herpetic neuralgia (PHN). However, RFT procedures' suboptimal pain relief and high occurrence of postoperative skin numbness present persistent challenges. Previous single-cohort research indicated that the low-temperature plasma coblation technique may potentially improve pain relief and reduce the incidence of skin numbness. Nevertheless, conclusive evidence favoring coblation over RFT is lacking.
OBJECTIVES
To compare the clinical outcomes associated with coblation to those associated with RFT in the treatment of refractory PHN.
STUDY DESIGN
Retrospective matched-cohort study.
SETTING
Affiliated Hospital of Capital Medical University.
METHODS
Sixty-eight PHN patients underwent coblation procedures between 2019 and 2020, and 312 patients underwent RFT between 2015 and 2020 in our department. A matched-cohort analysis was conducted based on the criteria of age, gender, weight, pain intensity, pain duration, side of pain, and affected thoracic dermatome. Pain relief was assessed using the numeric rating scale (NRS), the Medication Quantification Scale (MQS) Version III and the Neuropathic Pain Symptom Inventory (NPSI), which were employed to indicate pain intensity, medication burden, and comprehensive pain remission at 6, 12, and 24 months. Numbness degree scale scores and complications were recorded to assess safety.
RESULTS
We successfully matched a cohort of 59 patients who underwent coblation and an equivalent number of patients who underwent RFT as a PHN treatment. At the follow-up time points, both groups' NRS, MQS, and NPSI scores exhibited significant decreases from the pre-operation scores (P < 0.05). The coblation group's NRS scores were significantly lower than the RFT group's at the sixth and the twenty-fourth months (P < 0.05). At 24 months, the MQS values in the coblation group were significantly lower than those in the RFT group (P < 0.05). Furthermore, the coblation group's total intensity scores on the NPSI were significantly lower than the RFT group's at the 12- and 24-month follow-ups (P < 0.05). At 6 months, the coblation group's temporary intensity scores on the NPSI were significantly lower than the RFT group's (P < 0.05). Notably, the occurrence of moderate or severe numbness in the coblation group was significantly lower than in the RFT group at 6 and 12 months (P < 0.05). No serious adverse effects were reported during the follow-up.
LIMITATIONS
This analysis was a single-center retrospective study with a small sample size.
CONCLUSION
In this matched cohort analysis, coblation achieved longer-term pain relief with a more minimal incidence rate of skin numbness than did RFT. Further randomized controlled trials should be conducted to solidify coblation's clinical superiority to RFT as a PHN treatment.
Topics: Humans; Retrospective Studies; Neuralgia, Postherpetic; Male; Female; Middle Aged; Aged; Electrocoagulation; Spinal Nerve Roots; Pain Measurement
PubMed: 38805531
DOI: No ID Found