scholarly journals The Human SCN10AG1662S Point Mutation Established in Mice Impacts on Mechanical, Heat, and Cool Sensitivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Celeste Chidiac ◽  
Yaping Xue ◽  
Maria del Mar Muniz Moreno ◽  
Ameer Abu Bakr Rasheed ◽  
Romain Lorentz ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Radiant Heat ◽  
Mutant Mice ◽  
Tail Flick ◽  
Heat Sensitivity ◽  
Behavioral Tests ◽  
Fiber Density ◽  
Tail Flick Test ◽  
Nociceptive Neurons ◽  
Intraepidermal Nerve Fiber Density

The voltage-gated sodium channel NAV1.8 is expressed in primary nociceptive neurons and is involved in pain transmission. Mutations in the SCN10A gene (encoding NAV1.8 channel) have been identified in patients with idiopathic painful small fiber neuropathy (SFN) including the SCN10AG1662S gain-of-function mutation. However, the role of this mutation in pain sensation remains unknown. We have generated the first mouse model for the G1662S mutation by using homologous recombination in embryonic stem cells. The corresponding Scn10aG1663S mouse line has been analyzed for Scn10a expression, intraepidermal nerve fiber density (IENFD), and nociception using behavioral tests for thermal and mechanical sensitivity. The Scn10aG1663S mutants had a similar Scn10a expression level in dorsal root ganglia (DRG) to their wild-type littermates and showed normal IENFD in hindpaw skin. Mutant mice were more sensitive to touch than wild types in the von Frey test. In addition, sexual dimorphism was observed for several pain tests, pointing to the relevance of performing the phenotypical assessment in both sexes. Female homozygous mutants tended to be more sensitive to cooling stimuli in the acetone test. For heat sensitivity, male homozygous mutants showed shorter latencies to radiant heat in the Hargreaves test while homozygous females had longer latencies in the tail flick test. In addition, mutant males displayed a shorter reaction latency on the 54°C hot plate. Collectively, Scn10aG1663S mutant mice show a moderate but consistent increased sensitivity in behavioral tests of nociception. This altered nociception found in Scn10aG1663S mice demonstrates that the corresponding G1662 mutation of SCN10A found in SFN patients with pain contributes to their pain symptoms.

scholarly journals Inactivation of TNF-α ameliorates diabetic neuropathy in mice

2011 ◽  
Vol 301 (5) ◽  
pp. E844-E852 ◽  
Author(s):  
Isamu Yamakawa ◽  
Hideto Kojima ◽  
Tomoya Terashima ◽  
Miwako Katagi ◽  
Jiro Oi ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Caspase 3 ◽  
Tail Flick ◽  
Nerve Function ◽  
Fiber Density ◽  
Tail Flick Test ◽  
Intraepidermal Nerve Fiber Density ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Nerve Fiber Density

Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis of diabetic neuropathy. We inactivated TNF-α to determine if it is a valid therapeutic target for the treatment of diabetic neuropathy. We effected the inactivation in diabetic neuropathy using two approaches: by genetic inactivation of TNF-α (TNF-α−/− mice) or by neutralization of TNF-α protein using the monoclonal antibody infliximab. We induced diabetes using streptozotocin in wild-type and TNF-α−/− mice. We measured serum TNF-α concentration and the level of TNF-α mRNA in the dorsal root ganglion (DRG) and evaluated nerve function by a combination of motor (MNCV) and sensory (SNCV) nerve conduction velocities and tail flick test, as well as cytological analysis of intraepidermal nerve fiber density (IENFD) and immunostaining of DRG for NF-κB p65 serine-276 phosphorylated and cleaved caspase-3. Compared with nondiabetic mice, TNF-α+/+ diabetic mice displayed significant impairments of MNCV, SNCV, tail flick test, and IENFD as well as increased expression of NF-κB p65 and cleaved caspase-3 in their DRG. In contrast, although nondiabetic TNF-α−/− mice showed mild abnormalities of IENFD under basal conditions, diabetic TNF-α−/− mice showed no evidence of abnormal nerve function tests compared with nondiabetic mice. A single injection of infliximab in diabetic TNF-α+/+ mice led to suppression of the increased serum TNF-α and amelioration of the electrophysiological and biochemical deficits for at least 4 wk. Moreover, the increased TNF-α mRNA expression in diabetic DRG was also attenuated by infliximab, suggesting infliximab's effects may involve the local suppression of TNF-α. Infliximab, an agent currently in clinical use, is effective in targeting TNF-α action and expression and amelioration of diabetic neuropathy in mice.

The Local Antinociceptive Actions of Nonsteroidal Antiinflammatory Drugs in the Mouse Radiant Heat Tail-Flick Test

2007 ◽  
Vol 104 (4) ◽  
pp. 927-935 ◽  
Author(s):  
Ahmet Dogrul ◽  
S Ezgi G??lmez ◽  
M Salih Deveci ◽  
Husamettin Gul ◽  
Michael H. Ossipov ◽  
...  
Keyword(s):  
Radiant Heat ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Tail Flick ◽  
Antiinflammatory Drugs ◽  
Tail Flick Test

Ginger (Zingiber officinale Roscoe) Elicits Antinociceptive Properties and Potentiates Morphine-Induced Analgesia in the Rat Radiant Heat Tail-Flick Test

2010 ◽  
Vol 13 (6) ◽  
pp. 1397-1401 ◽  
Author(s):  
Reza Sepahvand ◽  
Saeed Esmaeili-Mahani ◽  
Ardeshir Arzi ◽  
Bahram Rasoulian ◽  
Mehdi Abbasnejad
Keyword(s):  
Zingiber Officinale ◽  
Radiant Heat ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Zingiber Officinale Roscoe

scholarly journals Evaluation of central and peripheral analgesic activity of amitriptyline in mice

2019 ◽  
Vol 8 (7) ◽  
pp. 1622
Author(s):  
Ishteyaque Ahmad ◽  
Md. Nazer Hasan ◽  
Ajitesh Kumar Mishra
Keyword(s):  
Analgesic Activity ◽  
Antidepressant Drug ◽  
Radiant Heat ◽  
Comparable Efficacy ◽  
Control Group ◽  
Tail Flick ◽  
Tail Flick Test ◽  
Writhing Test ◽  
Significant Difference ◽  
Tail Clip

Background: Pain is one of the most frequent reasons for visiting a doctor. Large-scale studies in Western countries have shown that a fifth of the adult population suffer from chronic pain. Treatment of pain, still a major problem in clinical practice. Despite several available analgesics, unrelieved pain remains a major health care issue. Amitriptyline is a tricyclic antidepressant drug, which is regarded as adjuvant analgesic. There is a common consensus among the researchers on analgesic effect of amitriptyline which is mediated by central pathway but for the peripheral mechanism no conclusive evidence exists till now.Methods: To establish the analgesic mechanism of amitriptyline we tried to evaluate the analgesic activity on different mice models for central (Radiant heat tail flick test and Haffner’s tail clip method) and peripheral analgesia (Writhing test). We also compare the effects of amitriptyline with standard drugs for central and peripheral analgesia.Results: Both in Radiant heat tail flick test and Haffner’s tail clip method we found that the amitriptyline showed significant (p<0.05 to p<0.001) activity as compared to control and diclofenac group. But in comparison to pentazocin group amitriptyline didn’t show significant difference in the reaction time. In acetic acid induced writhing test amitriptyline group mice showed 41.09% reduction in number of writhes as compared to control group. While the standard control (Diclofenac) showed reduction of 65.17% as compared to control. So, amitriptyline showed comparable efficacy towards reduction in number of writhes with that of diclofenac.Conclusions: The results revealed that amitriptyline has significant analgesic activity which is mediated by modulation of both the central and peripheral pathways.

scholarly journals TO STUDY THE ANTINOCICEPTIVE EFFECT OF CINNARIZINE ALONE AND IN COMBINATION WITH TRAMADOL IN ALBINO RATS BY TAIL FLICK METHOD

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Rajiv Kumar ◽  
Aasim Shakeel ◽  
Manju Gari ◽  
Uma Shankar Prasad Keshri
Keyword(s):  
Reaction Time ◽  
Opioid Analgesic ◽  
Antinociceptive Effect ◽  
Radiant Heat ◽  
Antinociceptive Activity ◽  
Albino Rats ◽  
Tail Flick ◽  
Withdrawal Time ◽  
Tail Flick Test ◽  
Standard Drug

Background: Pain is the most common reason for physician consultation in most countries. It is a major symptom in many medical conditions, and can interfere with a person's quality of life and general functioning. Acute pain is usually managed with medications such as analgesics and anesthetics. Cinnarizine is a piperazine derivative and Tramadol is an opioid analgesic. Cinnarizine is also a calcium channel blocker. So, in the present study an attempt has been made to access the antinociceptive activity of Cinnarizine alone & in combination with standard drug Tramadol with the hope of pharmacological synergism and better relief from pain. Material & Methods: 4 rats in 6 groups were weighed & colour coded. Basal reaction time to radiant heat was taken. Tail withdrawal time was recorded as the end point. Reaction time was taken at 0, 30 & 60 minutes on day 0, 7, 14, 21 & 28. Result: All observation were done by the ANOVA followed by post hoc Tukey’s. It is seen that Cinnarizine alone (in both doses) has antinociceptive activity but that is not statistically significant. But when it is given along with Tramadol it potentiates antinociceptive activity of Tramadol which is statistically significant. Conclusion: The result of this study conclude that Cinnarizine alone has antinociceptive activity in both doses (i.e 2.5mg/kg & 5mg/kg) but it is statistically not significant. Tramadol shows higher antinociception with Cinnarizine in dose of 5mg/kg than with 2.5mg/kg. Keywords: Antinociception, Cinnarizine, Tramadol, Tail flick test, Albino rats

scholarly journals Analgesic and Antipyretic Activities of Methanol Extract and Its Fraction from the Root ofSchoenoplectus grossus

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nirmal Kumar Subedi ◽  
S. M. Abdur Rahman ◽  
Mohammad Ahsanul Akbar
Keyword(s):  
Acetic Acid ◽  
Petroleum Ether ◽  
Methanol Extract ◽  
Diclofenac Sodium ◽  
Radiant Heat ◽  
Tail Flick ◽  
Dependent Manner ◽  
Tail Flick Test ◽  
Standard Drug ◽  
Pain Models

The study aims to evaluate analgesic and antipyretic activities of the methanol extract and its different fractions from root ofSchoenoplectus grossususing acetic acid induced writhing and radiant heat tail flick method of pain models in mice and yeast induced pyrexia in rats at the doses of 400 and 200 mg/kg. In acetic acid writhing test, the methanol extract, petroleum ether, and carbon tetrachloride fractions produced significant (P<0.001andP<0.05) inhibition of writhing responses in dose dependent manner. The methanol extract at 400 and 200 mg/kg being more protective with 54% and 45.45% of inhibition compared to diclofenac sodium of 56% followed by petroleum ether fractions of 49.69% and 39.39% at the same doses. The extracts did not produce any significant antinociceptive activity in tail flick test except standard morphine. When studied on yeast induced pyrexia, methanol and petroleum ether fractions significantly lowered the rectal temperature time dependently in a manner similar to standard drug paracetamol and distinctly more significant (P<0.001) after second hour. These findings suggest that the root extracts ofS. grossuspossess significant peripherally acting analgesic potential and antipyretic property. The phytochemical screening showed the presence of flavonoids, alkaloids, and tannins.

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