Nitrous Oxide Revisited

2005 ◽  
Vol 103 (4) ◽  
pp. 845-854 ◽  
Author(s):  
Philippe Richebé ◽  
Cyril Rivat ◽  
Cyril Creton ◽  
Jean-Paul Laulin ◽  
Pierre Maurette ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Morphine Tolerance ◽  
Acute Tolerance ◽  
Dependent Manner ◽  
Analgesic Effects ◽  
Pain Models ◽  
Opioid Induced Hyperalgesia ◽  
Incisional Pain ◽  
Fentanyl Administration ◽  
Dose Dependent

Background Although opioids are unsurpassed analgesics for surgery, they also induce an N-methyl-D-aspartate-dependent enhancement of postoperative hyperalgesia. Because nitrous oxide (N2O) has anti-N-methyl-D-aspartate properties, the purpose of this study was to evaluate nitrous oxide ability to prevent such an opioid-induced hyperalgesia in rats. Methods First, preventive effects of 50/50% N2O-O2 on the development of delayed hyperalgesia observed after inflammatory pain (hind paw carrageenan injection on D0) were examined for several days. Second, the ability of nitrous oxide (10-40%) to limit opioid-induced hyperalgesia induced by fentanyl was evaluated in nonsuffering rats. Third, antihyperalgesic effects of various nitrous oxide concentrations (20-50%) were assessed in both inflammatory and incisional pain models in fentanyl-treated rats (4 x 100 microg/kg subcutaneously). Finally, the analgesic effect of a single dose of morphine was evaluated 24 h after fentanyl administration and nitrous oxide (D0) to assess its preventive effect on acute morphine tolerance in both nonsuffering and hind paw-incised rats. Results When applied on D0, nitrous oxide reduced delayed hyperalgesia induced by inflammation. Exposure to nitrous oxide on D0 also reduced opioid-induced hyperalgesia in nonsuffering rats in a dose-dependent manner. In fentanyl-treated rats with inflammatory or incisional pain, nitrous oxide strongly limited both magnitude and duration of hyperalgesia. Moreover, nitrous oxide exposure on D0 opposed development of acute tolerance to analgesic effects of morphine administered on D1 in both nonsuffering and incised fentanyl-treated rats. Conclusions Nitrous oxide, an N-methyl-D-aspartate receptor antagonist, prevented the enhancement of pain sensitivity induced by both nociceptive inputs and fentanyl and opposed acute morphine tolerance. Results suggest that perioperative nitrous oxide use reduces exaggerated postoperative pain and morphine consumption.

scholarly journals The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Aminobutyric Acid ◽  
Thermal Stimulus ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Analgesic Effects ◽  
Nociceptive Stimulus ◽  
Dose Dependent

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.

Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane 

1998 ◽  
Vol 88 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Malcolm Daniel ◽  
Richard B. Weiskopf ◽  
Mariam Noorani ◽  
Edmond I. Eger
Keyword(s):  
Nitrous Oxide ◽  
Cardiovascular Response ◽  
Dependent Manner ◽  
Surgical Incision ◽  
Arterial Blood ◽  
Adrenergic Response ◽  
The Mean ◽  
End Tidal ◽  
Inhaled Anesthetic ◽  
Dose Dependent

Background Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner. Methods Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 microg/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group. Results Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P &gt; 0.05) and decreased MAP (P &lt; 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P &gt; 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 microg/kg intravenously equivalently (P &gt; 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P &lt; 0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P &lt; 0.05), but a further increase in fentanyl to 3 microg/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC). Conclusions Clinically attainable doses of desflurane and isoflurane, in 60% nitrous oxide (0.55 MAC), block the cardiovascular response to surgical incision at 1.3 MAC. Fentanyl given at 1.5 microg/kg decreases the MAC-BAR for each agent with no further decrease produced by 3 microg/kg fentanyl.

scholarly journals Antinociceptive Effects of Sinomenine Combined With Ligustrazine or Paracetamol in Animal Models of Incisional and Inflammatory Pain

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianle Gao ◽  
Tao Li ◽  
Wei Jiang ◽  
Weiming Fan ◽  
Xiao-Jun Xu ◽  
...  
Keyword(s):  
Animal Models ◽  
Inflammatory Pain ◽  
Extracellular Fluid ◽  
Postoperative Pain Management ◽  
Assay Method ◽  
Pharmacokinetic Studies ◽  
Analgesic Effects ◽  
Pain Models ◽  
Potential Benefits ◽  
Incisional Pain

The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.

scholarly journals Anti-arthralgic activity of the n-hexane extract (HTp) of yellow oleander seeds; Thevetia peruviana (Pers.) K. Schum

2021 ◽  
Author(s):  
Joy Ifunanya Odimegwu ◽  
Fatiha Oyebola Olabisi
Keyword(s):  
Scientific Evidence ◽  
Positive Control ◽  
Test Subject ◽  
Dependent Manner ◽  
Thevetia Peruviana ◽  
Relieve Pain ◽  
Pain Models ◽  
Hexane Extracts ◽  
Cardioactive Glycosides ◽  
Dose Dependent

Thevetia peruviana (Pers.) K.Schum. (Apocynaceae) seeds are known to possess cardioactive glycosides such as thevetin A, thevetin B, nerifolin etc. They are also used locally for general pain relief for which there is no scientific evidence to our knowledge. Arthralgia is regarded generally as pain without inflammation. It is endemic in the society and sufferers continue to imbibe pain relieving drugs in their tons all over the world. Analgesic activity test was carried out using the formalin-induced pain models, at 0.1g, 0.2g and 0.3g/kg doses of n-hexane extracts of Thevetia peruviana seeds (HTp) in Wistar mice. Diclofenac was used as positive control. Acute toxicity test was carried out at doses of 1000, 2500 and 5000 mg/kg weight of test subject. It was observed that HTp at concentrations of 0.1g, 0.2g and 0.3g/kg showed significant analgesic effect at compared to the control. The percentage inhibition observed was 29.60%, 44.80% and 50.72% for the early pain phase and 100% for the late pain phase respectively, indicating HTps NSAID-like property. HTp showed the highest percentage inhibition at 300 mg/kg (50.72 %) and significant; P < 0.005 pain reduction. HTp did not produce any toxicity up to a dose of 5000 mg/kg weight which is very interesting as the seeds are known for their toxicity due to the cardiac glycoside presence. The results of the study suggest that HTp does indeed relieve pain significantly in a dose dependent manner, thus justifying its use in management of arthralgia. Keywords: Arthralgia, Herbal medicine, Pain,Thevetia peruviana, yellow oleander

scholarly journals Nitrous oxide causes peripheral neuropathy in a dose dependent manner among recreational users

2019 ◽  
Vol 34 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Adam R Winstock ◽  
Jason A Ferris
Keyword(s):  
Nitrous Oxide ◽  
Peripheral Neuropathy ◽  
Dependent Manner ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Gender And Age ◽  
And Gender ◽  
Not At Risk ◽  
The Relationship ◽  
Dose Dependent

Background: Nitrous oxide (N2O) has been used in clinical and recreational settings for over 150 years. Through inactivation of the Vitamin B12 dependent enzyme, methionine synthase, N2O can lead to the development of peripheral neuropathy. This study sought to determine the relationship between the exposure and risk of neurological symptoms in the largest ever sample of users. Design: Data are drawn from the Global Drug Survey (GDS) over three consecutive years (2014–2016). The Global Drug Survey is an online, cross-sectional survey of substance use, translated into multiple languages. Participants: Respondents to the Global Drug Survey who provided details on N2O use and the experience of paraesthesia in the previous 12 months. Measurements: Questions relating to N2O use, peripheral neuropathy, age and gender were explored among last year’s users. Findings: Of 241,566 respondents, 41,181 (17.0%) indicated that they had ever used nitrous oxide; of these, 42.1% had used in the last 12 months. For the final model, data from 16,124 participants who had used N2O in the last 12 months and had provided responses on age, dose, gender and paraesthesia were used. Of these, the number of respondents reporting persistent numbness/tingling (paraesthesia) in their hands or feet was 537 (3.3%). Although the risk was very low among infrequent users, there was a strong dose–response relationship. For people indicating one or two doses per session, the probability of reporting paraesthesia was approximately 0.018 by comparison; for people indicating 100 doses per session the probability was approximately 0.085. The association, between dose and paraesthesia was influenced by gender and age. Conclusion: While infrequent, episodic users are not at risk, a minority of heavy users are at dose-dependent risk of developing serious neurological consequences. Better education and raised awareness of early symptoms are required.

scholarly journals (-)-Englerin-A Has Analgesic and Anti-Inflammatory Effects Independent of TRPC4 and 5

2021 ◽  
Vol 22 (12) ◽  
pp. 6380
Author(s):  
João de Sousa Valente ◽  
Khadija M Alawi ◽  
Sabah Bharde ◽  
Ali A. Zarban ◽  
Xenia Kodji ◽  
...  
Keyword(s):  
Thermal Hyperalgesia ◽  
Dependent Manner ◽  
Drg Neurons ◽  
East African ◽  
Cellular Mechanisms ◽  
Analgesic Effects ◽  
Englerin A ◽  
Anti Inflammatory ◽  
Dose Dependent

Recently, we found that the deletion of TRPC5 leads to increased inflammation and pain-related behaviour in two animal models of arthritis. (-)-Englerin A (EA), an extract from the East African plant Phyllanthus engleri has been identified as a TRPC4/5 agonist. Here, we studied whether or not EA has any anti-inflammatory and analgesic properties via TRPC4/5 in the carrageenan model of inflammation. We found that EA treatment in CD1 mice inhibited thermal hyperalgesia and mechanical allodynia in a dose-dependent manner. Furthermore, EA significantly reduced the volume of carrageenan-induced paw oedema and the mass of the treated paws. Additionally, in dorsal root ganglion (DRG) neurons cultured from WT 129S1/SvIm mice, EA induced a dose-dependent cobalt uptake that was surprisingly preserved in cultured DRG neurons from 129S1/SvIm TRPC5 KO mice. Likewise, EA-induced anti-inflammatory and analgesic effects were preserved in the carrageenan model in animals lacking TRPC5 expression or in mice treated with TRPC4/5 antagonist ML204.This study demonstrates that while EA activates a sub-population of DRG neurons, it induces a novel TRPC4/5-independent analgesic and anti-inflammatory effect in vivo. Future studies are needed to elucidate the molecular and cellular mechanisms underlying EA’s anti-inflammatory and analgesic effects.

Analgesic Mechanisms of Ketamine in the Presence and Absence of Peripheral Inflammation

2000 ◽  
Vol 93 (2) ◽  
pp. 520-528 ◽  
Author(s):  
Tomoyuki Kawamata ◽  
Keiichi Omote ◽  
Hajime Sonoda ◽  
Mikito Kawamata ◽  
Akiyoshi Namiki
Keyword(s):  
Radiant Heat ◽  
Contralateral Side ◽  
Peripheral Inflammation ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Inhibitory System ◽  
Analgesic Effects ◽  
Antinociceptive Effects ◽  
Lumbar Cerebrospinal Fluid ◽  
Dose Dependent

Background The studies on the mechanisms of ketamine antinociception have led to conflicting results. In this study, the authors investigated the contribution of supraspinal monoaminergic descending inhibitory system to ketamine analgesia for acute nociception and inflammation-induced hyperalgesia. Methods Male Sprague-Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive threshold. The analgesic effects of intrathecal or intraperitoneal ketamine were examined in the rats that received unilateral intraplantar carrageenan and in those that were untreated. In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine. Using an intrathecal microdialysis method, noradrenaline and 5-hydroxytryptamine concentrations in lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both saline- and carrageenan-treated rats. Results In the untreated rats, intraperitoneal but not intrathecal ketamine produced antinociceptive effects in a dose-dependent manner. Pretreatment with intrathecal yohimbine or methysergide inhibited these antinociceptive effects. Intraplantar carrageenan significantly reduced paw withdrawal latencies on the injected paw but not on the contralateral paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw withdrawal latencies on the injected side in a dose-dependent manner without any effects on the contralateral side. Neither yohimbine nor methysergide inhibited these antihyperalgesic effects. In analyses of monoamines, the magnitude of increase in monoamines after intraperitoneal ketamine was significantly smaller in the carrageenan-treated rats than in the saline-treated rats. Conclusion These results demonstrated that ketamine produced antinociceptive effects through an activation of the monoaminergic descending inhibitory system, whereas, in a unilateral peripheral inflammation-induced hyperalgesic state, the monoaminergic system did not contribute to the antihyperalgesic effects of ketamine. The mechanisms of the antinociceptive and antihyperalgesic properties of ketamine are different.

scholarly journals In VitroandIn VivoCharacterization of the New Analgesic Combination Beta-Caryophyllene and Docosahexaenoic Acid

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Paolo Fiorenzani ◽  
Stefania Lamponi ◽  
Agnese Magnani ◽  
Ilaria Ceccarelli ◽  
Anna Maria Aloisi
Keyword(s):  
Docosahexaenoic Acid ◽  
Gonadal Hormones ◽  
Male Rats ◽  
Dependent Manner ◽  
Recurrent Pain ◽  
Analgesic Effects ◽  
Animal Pain ◽  
Pain Models

Beta-caryophyllene (BCP) and docosahexaenoic acid (DHA) are components of several plants with documented anti-inflammatory and analgesic effects in animal pain models. In the present study,in vitroandin vivotests were carried out to evaluate their effects, alone or in combination, during long-lasting administration in a model of persistent pain. IR spectra of the two compounds were obtained to determine their chemical stability and thenin vitrotoxicity was evaluated in fibroblasts and astrocytes. In thein vivotests, the analgesic effects of BCP and BCP+DHA were determined in male rats subjected to a model of persistent recurrent pain (three repetitions of the formalin test once a week) to mimic recurrent pain. Both substances were administeredper osin almond oil for 2 weeks. Gonadal hormones were determined at the end of the tests to evaluate treatment-induced effects on their levels. BCP changed fibroblast and astrocyte survival in a dose-dependent manner and the effect was counteracted by DHA coadministration. In thein vivotests, pain responses were significantly decreased in the BCP and BCP+DHA groups with respect to OIL after 1 and 2 weeks of treatment. Estradiol and testosterone levels were increased only in the BCP group. In conclusion, BCP alone or at lower concentration in combination with DHA was efficacious in modulating pain, showing a clear analgesic activity.

scholarly journals Phytochemical Analysis, Antioxidant and Analgesic Activities of Incarvillea compacta Maxim from the Tibetan Plateau

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1692 ◽  
Author(s):  
Jiajia Guo ◽  
Dan Zhang ◽  
Chao Yu ◽  
Ling Yao ◽  
Zhuo Chen ◽  
...  
Keyword(s):  
Water Extract ◽  
Control Group ◽  
Phytochemical Analysis ◽  
Second Phase ◽  
The Tibetan Plateau ◽  
Dependent Manner ◽  
Hot Plate Test ◽  
Analgesic Effects ◽  
Analgesic Activities ◽  
Dose Dependent

Incarvillea compacta Maxim is a traditional Tibetan plant widely used to treat rheumatic pain and bruises. We conducted qualitative analyses by liquid chromatography-mass spectrometry and quantitative analyses of the total phenols, flavonoids, and alkaloids content of different extracts of I. compacta Maxim. Antioxidant and analgesic activity were analyzed. The results showed that the methanol extract had the highest content of the various ingredients. A total of 25 constituents were identified, of which compounds 1–23 were found for the first time in this plant. The water extract had the highest capacity to clear free radicals in the antioxidant test. The water extract had dose-dependent analgesic effects in the first and second phase in a formalin test. The latency of pain from a hot-plate test was augmented by the water extract when the dose was greater than or equal to 30 g/kg. The water extract significantly decreased the amount of writhing in a dose-dependent manner compared with the control group in the acetic acid-induced writhing test. These results showed that I. compacta Maxim is a new antioxidant and analgesic agent, and this study provides information on its ingredients for further study.

scholarly journals Antinociceptive Effect of Single Components Isolated from Agrimonia pilosa Ledeb. Extract

2019 ◽  
Vol 87 (3) ◽  
pp. 18
Author(s):  
Jing Hui Feng ◽  
Hee Jung Lee ◽  
Set Byeol Kim ◽  
Jeon Sub Jung ◽  
Soon Sung Lim ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Formalin Injection ◽  
Second Phase ◽  
Dependent Manner ◽  
Thermal Pain ◽  
Icr Mice ◽  
Chemically Induced ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Dose Dependent

Agrimonia pilosa Ledeb. produces an antinociceptive effect in ICR mice in both chemically induced and thermal pain models. In the present study, we examined the antinociceptive effects of single components isolated from Agrimonia pilosa Ledeb. (AP) extract in ICR mice. Three active compounds isolated from AP, including rutin, luteolin-7-O-glucuronide, and apigenin-7-O-glucuronide, were isolated and identified by comparing EI-MS, 1H-, 13C-NMR, and UV. We studied the antinociceptive effects of three single components administered orally at doses of 10 and 20 mg/kg in monosodium urate (MSU)-treated pain model as measured by von Frey test. Among these compounds, apigenin-7-O-glucuronide was more effective in the production of antinociceptive effects. We further characterized the antinociceptive effects and possible mechanisms of apigenin-7-O-glucuronide in writhing and formalin tests. Oral administration of Apigenin-7-O-glucuronide caused a reduction in the number of writhing and effectively reduced the pain behavior observed during the second phase of the formalin test in a dose-dependent manner. In addition, the pretreatment of yohimbine instead of naloxone or methysergide attenuated apigenin-7-O-glucuronide-induced antinociception in the writhing test. Moreover, apigenin-7-O-glucuronide caused reduction in the expression of p-P38, p-CREB, and p-mTOR induced by formalin injection. Our results indicate that apigenin-7-O-glucuronide shows an antinociceptive effect in various pain models. In addition, spinal α2-adrenergic receptors appear to be involved in the production of antinociception induced by apigenin-7-O-glucuronide. Furthermore, the antinociceptive effect of apigenin-7-O-glucuronide appears to be mediated by reduction in the expression of p-P38, p-CREB and p-mTOR levels in the spinal cord.

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