scholarly journals Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: A Dose-Dependent Effect

2015 ◽  
Vol 20 (6) ◽  
pp. 309-315 ◽  
Author(s):  
Meric Ben Boujema ◽  
Emilie Laboureyras ◽  
Jan Pype ◽  
Baptiste Bessière ◽  
Guy Simonnet

BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of theN-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief.METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats.RESULTS: Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg/kg to 300 mg/kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O.CONCLUSIONS: These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies.

1994 ◽  
Vol 40 (3) ◽  
pp. 45-47
Author(s):  
L. V. Tarasenko ◽  
S. V. Varga ◽  
V. N. Demchenko ◽  
Ye. V. Bolshova ◽  
N. D. Nosenko ◽  
...  

Radioactive 131Iwas injected in single doses 9.25, 37, and 92.5 kBq to prepubertal (30-day-old) male rats. Iodine incorporation in doses 37 and 92.5 kBq resulted in some functional changes in the reproductive system of mature rats: blood testosterone level increased, its hypothalamic aromatization intensified, and biologically active LH level in the blood dropped. Incorporation of 9.25 kBq of 131-I had no effect on male reproductive system. A possibility of direct injury to rat testicles by 131I incorporation is suggested.


Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Adithya Srikanthan ◽  
Teresa Maietta ◽  
Abigail Hellman ◽  
Vraj Patel ◽  
Alicia Clum ◽  
...  

Abstract INTRODUCTION Various rodent models have long been employed to study treatments for chronic pain. However, these studies have resulted in unsuccessful phase-I and II human trials that have failed to result in viable options for patients. Though limitations of animal models are no doubt one issue, lack of objective markers corresponding with pain relief play a role. Our lab has shown significant pain relief in a common peroneal nerve injury (CPNI) rat model following administration of external pulsed low-intensity focused ultrasound (liFUS), thus, establishing external liFUS as a promising technique for treatment of neuropathic pain. Current knowledge of liFUS effects are limited to observable behavioral changes, and little is known of the mechanism of action. To successfully translate this device into the clinic, we examine molecular changes in the inflammatory cascade. METHODS Male rats underwent CPNI to induce neuropathic pain. External liFUS treatment was performed on the L5 dorsal root ganglion (DRG) in the neuropathic model, which was determined from responses to Von Frey fibers (VFF). 24 h post liFUS treatment, L5 DRGs were obtained from 4 distinct cohorts: rats that underwent CPNI with liFUS, CPNI with sham liFUS, sham CPNI with liFUS, and sham CPNI sham liFUS (n = 4 for each group). Using a membrane-based sandwich immunoassay (Proteome Profiler Rat Cytokine Array Kit from R&D System), we assessed relative abundances of 6 anti-inflammatory cytokines and 16 pro-inflammatory cytokines. RESULTS CPNI resulted in an 82.5% decrease of tumor necrosis factor alpha (TNFa) and a 61.8% increase of macrophage inflammatory protein 1-alpha (MIP-1a). liFUS led to a 60% decrease in MIP-1a and a 40% increase in TNFa. Other changes in cytokines were not affected by CPNI or liFUS. CONCLUSION liFUS resulted in similar changes in TNFa and MIP-1a, as compared to spinal cord stimulation and other medical treatments for pain syndromes. Further work will examine inflammatory responses over time and in female rats.


2013 ◽  
Vol 5;16 (5;9) ◽  
pp. E577-E589
Author(s):  
Ying-Wei Wang

Background: Neuropathic pain induction by nerve injury has been shown by in vitro studies to be accompanied by synaptic strengthening in the anterior cingulate cortex (ACC) and has been shown by pharmacological studies in vivo to be prevented by blocking N-methyl-D-aspartate (NMDA) receptor-dependent ACC plasticity. These findings indicate that ACC neurons undergo nerve injury-induced synaptic modifications and further raise a new question about neuropathic pain-associated changes in neuronal activity in the ACC in vivo, particularly spontaneous neuronal oscillations – a process believed to be fundamental for many forms of brain function. Objective: In this study, we examined the change of spontaneous membrane-potential (MP) oscillations in the ACC in vivo in a neuropathic pain animal model of chronic constriction injury (CCI), which may account for neuropathic pain development, as well as pain hypersensitivity and spontaneous pain. Study Design: Experimental trial in rats. Methods: Neuropathic pain rats were produced by CCI surgery on the common sciatic nerve. Neuropathic pain-related behaviors were accessed by evoked responses to both mechanical and thermal stimuli, as well as spontaneous pain indicated by spontaneous foot lifting. In vivo wholecell recording was performed in both control and neuropathic pain rats under anaesthesia. MP and action-potential (AP) changes of layer II/III ACC pyramidal cells were measured in current-clamp mode. The level of anaesthesia was evaluated by monitoring respiratory and heart rates in some experiments. Results: Within 7 to 14 days after CCI surgery, the frequency of MP oscillations of ACC neurons was found to be significantly higher than that in control rats. Such an increase in oscillation frequency after surgery was not due to periphery transmission via the sciatic nerve subjected to CCI surgery and was indicated to be accounted for by neuronal modifications in the central nervous system. Furthermore, this increase was found to result in a higher overall level of MP excitation as well as an increase in spontaneous AP firing. Limitations: Our findings in MP and AP changes were obtained in anaesthetized brains; this issue remains to be further examined by using whole-cell recording in awake behaving animals. Conclusions: Neuropathic pain is accompanied by the increase in rates of spontaneous oscillations of ACC neurons. This change may be critical for neuropathic pain development, as well as pain hypersensitivity and spontaneous pain in neuropathic pain animals. Key Words: Neuropathic pain, anterior cingulate cortex, spontaneous activity, neuronal oscillation, chronic constriction injury


2020 ◽  
Vol 35 (9) ◽  
pp. 1989-1998
Author(s):  
Mohamed Salaheldien Mohamed Alayat ◽  
Mohammad Abubakar Basalamah ◽  
Wagih Gamal Eldin Abd-Elghany Elbarrany ◽  
Naser Ahmed Mahmoud El-Sawy ◽  
Ehab Mohamed Abdel-Kafy ◽  
...  

2000 ◽  
Vol 86 (3) ◽  
pp. 941-946 ◽  
Author(s):  
Josephine F. Wilson ◽  
Nicole R. Nugent ◽  
Jonathan E. Baltes ◽  
Sayaka Tokunaga ◽  
Tarik Canic ◽  
...  

To date, the effect of low doses of caffeine on aggression has not been systematically examined. Doses of caffeine greater than 30 mg/kg appear to reduce social interaction and aggression in all species studied. In a double blind study of the effects of low doses of caffeine on aggression, rats were housed four per cage, and aggressive behavior against an intruder was recorded during baseline and following administration of 2.5, 5, 10, and 20 mg/kg caffeine. Aggressive behavior was significantly increased following administration of the higher doses of caffeine. Doses of 5, 10, and 20 mg/kg caffeine all were effective in increasing pushing behavior, whereas doses of 5 and 10 mg/kg were most effective in increasing boxing behavior, and a dose of 10 mg/kg was significantly more effective than other doses in increasing chasing and roll-tumble-bite behaviors. Based on these results and other published reports, the inverted-U shaped dose-dependent effect of caffeine on aggression appears to apply, with aggressive behavior being most elevated following doses of 5–20 mg/kg caffeine, less elevated following 2.5 mg/kg or 30 mg/kg, and significantly reduced with doses above 40 mg/kg and at doses below 2.5 mg/kg.


Author(s):  
Shiva Naseri ◽  
Gabriele Griffanti ◽  
William C. Lepry ◽  
Vimal B. Maisuria ◽  
Nathalie Tufenkji ◽  
...  

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