RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

Magar, Shital; Nayak, Deepika; Mahajan, Umesh B; Patil, Kiran; Shinde, Sachin D.; Goyal, Sameer N.; Swaminarayan, Shivang; Patil, Chandragouda R.; Ojha, Shreesh; Kundu, Chanakya Nath

doi:10.1038/s41598-018-31971-9

Cited by 10 publications

(5 citation statements)

References 57 publications

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“…It is noted that TNF-a plays an important role in regulating neuropathic pain in vivo experiments using various animal models. 17,[26][27][28][29] The mechanisms by which TNF-a mediates mechanical and thermal hyperalgesia include a direct sensitization effect of TNF-a and/or sensitization of inflammatory mediators evoked by TNF-a on ion channels in sensory neurons. 14,15 TNFa activates multiple signaling pathways, including the p38-MAPK and JNK pathways, 9 which are recognized as important regulators of inflammatory pain.…”

Section: Discussionmentioning

confidence: 99%

Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1

et al. 2019

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Background Pain is one of the most common and distressing symptoms suffered by patients with progression of bone cancer; however, the mechanisms responsible for hyperalgesia are not well understood. The purpose of our current study was to determine contributions of the sensory signaling pathways of inflammatory tumor necrosis factor-α and interleukin-6 and downstream transient receptor potential ankyrin 1 (TRPA1) to neuropathic pain induced by bone cancer. We further determined whether influencing these pathways can improve bone cancer pain. Methods Breast sarcocarcinoma Walker 256 cells were implanted into the tibia bone cavity of rats to induce mechanical and thermal hyperalgesia. ELISA and western blot analysis were used to examine (1) the levels of tumor necrosis factor-α and interleukin-6 in dorsal root ganglion and (2) protein expression of tumor necrosis factor-α and interleukin-6 receptors (TNFR1 and IL-6R) and TRPA1 as well as intracellular signals (p38-MAPK and JNK). Results Tumor necrosis factor-α and interleukin-6 were elevated in the dorsal root ganglion of bone cancer rats, and expression of TNFR1, IL-6R, and TRPA1 was upregulated. In addition, inhibition of TNFR1 and IL-6R alleviated mechanical and thermal hyperalgesia in bone cancer rats, accompanied with downregulated TRPA1 and p38-MAPK and JNK. Conclusions We revealed specific signaling pathways leading to neuropathic pain during the development of bone cancer, including tumor necrosis factor-α-TRPA1 and interleukin-6-TRPA1 signal pathways. Overall, our data suggest that blocking these signals is beneficial to alleviate bone cancer pain.

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Section: Discussionmentioning

confidence: 99%

Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1

et al. 2019

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“…q) This conductive aspect may also enable permanent pattern imprinting of molecular vibration in the water-layer structure and therefore may also explain the memory aspects of activated water that have been recently shown in independent reports (Montagnier et al, 2017;Magar et al, 2018, Tang et al, 2018.…”

Section: Discussionmentioning

confidence: 82%

“…Coherent imprints induce specific polymerase activity as if the physical DNA segments were present (see Figure 9). This idea is supported by a recent report in Nature (Magar et al 2018) showing that an aqueous solution of a toxin can be ultra-diluted without losing its pharmacological activity. Both studies may imply that somehow activity is stored in coherent domains of the water molecular matrix due to the previous interaction with the specific 3-D conformation (in-formation) of these protein structures.…”

Section: Water Molecules Affect Bio-molecular Processesmentioning

confidence: 80%

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2020

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This paper addresses the question whether electromagnetic frequencies associated with pure water are similar to those of biological systems. A literature survey was performed on intrinsic frequencies of water molecules measured across the electromagnetic spectrum using various spectroscopic technologies. The registered frequencies were plotted on an algorithmic generalized music (GM) scale, described by a quantum entangled wave function, and compared with earlier detected electromagnetic frequency patterns revealed in various biological systems. The meta-analysis shows that semi-harmonic frequency patterns found in purified water are very similar to those found in biological systems. A metaanalysis of about 700 measured frequencies of pure water shows that 192 subsequent first and second derivatives of spectral frequency curves of water molecules can be precisely positioned at the proposed lines of the calculated pattern of coherent eigenfrequencies with an error of 0.45% and statistical significance of p < 0.02. A new order parameter characteristic for water molecule assembly has been revealed, which implies quantum coherency and entanglement. This is in line with the already evidenced and published universal order that we called the GM-scale. Following these findings, we may assume that water molecule assembly shows electromagnetic and electronic collective states that contain "quantum imprints or molds" for living cells. A potential explanation for this feature is that water molecules are ordered in a partially distorted tetrahedral geometry, which yields a specific network structure. Since water molecules have a comparable distribution of coherent electromagnetic field (EMF) bands to that of fluid assemblies in living cells, a resonant wave interaction is expected between the cytoplasm and surrounding water molecules. Evidence of a new quantum wave equation of coherence for water molecules has been found, that is defined as a physical principle: E n = ħ ω ref 2 n+p 3 m .

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“…These injuries have been shown to be the basis of aging, neurodegenerative diseases and tumorigenesis [36]. At present, the removal of excessive ROS has also been considered as an effective treatment for neuropathic pain [37]. The mechanisms of pain relief mainly include increased intracellular Ca 2+ , phosphorylation of NMDA receptors and up-regulation of apoptotic genes, such as bax, caspase-3, caspase-9 and apoptotic protease-activating factor-1 (Apaf-1).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviated neuropathic pain in dorsal root ganglion neurons by inhibition of anaerobic glycolysis activity and enhancement of ROS tolerance

et al. 2020

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Neuropathic pain is a kind of chronic pain that is triggered or caused primarily by damage to the nervous system and neurological dysfunction. It’s known that dexmedetomidine is a new type of highly selective alpha2-adrenoceptor agonist with sedation, anti-anxiety, analgesic and other effects. However, the function and mechanism of dexmedetomidine on neuropathic pain are not clear. Rat DRG neurons were isolated and identified using immunofluorescence assay. Following treatment with H2O2, dexmedetomidine or ROS inhibitor (NAC), the apoptosis and ROS levels were examined by flow cytometery; apoptosis- and anaerobic glycolysis-related proteins were determined by Western blot assay; glucose consumption, pyruvic acid, lactic acid and ATP/ADP ratios were also measured. The results revealed that dexmedetomidine inhibited H2O2-induced apoptosis and reactive oxygen species (ROS) in rat DRG neurons and in addition, dexmedetomidine down-regulated the expression levels of anaerobic glycolysis-related proteins, significantly reduced glucose, pyruvic acid and lactic acid levels. It also increased the ATP/ADP ratio in H2O2-treated rat dorsal root ganglion (DRG) neurons. Moreover, we also demonstrated that ROS inhibitor (NAC) also inhibited H2O2-induced apoptosis and anaerobic glycolysis in rat DRG neurons. In conclusion, dexmedetomidine suppressed H2O2-induced apoptosis and anaerobic glycolysis activity by inhibiting ROS, in rat DRG neurons. Therefore, dexmedetomidine might play a pivotal role in neuropathic pain by the inhibition of ROS.

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RETRACTED ARTICLE: Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats

Cited by 10 publications

References 57 publications

Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1

Roles of tumor necrosis factor-α and interleukin-6 in regulating bone cancer pain via TRPA1 signal pathway and beneficial effects of inhibition of neuro-inflammation and TRPA1

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Dexmedetomidine alleviated neuropathic pain in dorsal root ganglion neurons by inhibition of anaerobic glycolysis activity and enhancement of ROS tolerance

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