Papers by Baptiste Bessière
Pain, 2021
ABSTRACT Experimental studies have suggested that nitrous oxide-induced analgesia depends on inte... more ABSTRACT Experimental studies have suggested that nitrous oxide-induced analgesia depends on interactions with opioids. On the basis of these results, we hypothesized that the effects of inhaled nitrous oxide/oxygen (N2O/O2) 50%-50% equimolar mixture (EMONO) on patients with neuropathic pain would be higher in those receiving concomitant opioids. To test this hypothesis, we did exploratory post hoc analyses of our recently published ProtoTOP study to compare the effects of EMONO and placebo in patients with or without concomitant opioid treatment. A total of 92 patients of the 221 (ie, 41.6%) included in the ProtoTOP study were concomitantly treated with opioids. In contrast with our previous analyses, average pain intensity was significantly decreased in comparison with placebo one week after the last treatment administration in patients treated with opioids, but not in those treated without opioid, and this effect was maintained over the 4-week follow-up period. Neuropathic pain symptom inventory (NPSI total and subscores) was also significantly more decreased after inhalation of EMONO in comparison with placebo only in patients receiving opioids. The proportion of patients with at least 30% pain reduction and of those reporting an overall improvement with the Patient Global Impression of Change were significantly higher only in this population of patients. In conclusion, these results complement our previous analyses with the identification of a specific population of responders to EMONO inhalation in patients with neuropathic pain. As suggested by experimental studies, we hypothesized that these long-lasting analgesic effects could depend on the anti-N-methyl-D-aspartate properties of N2O.
Received Address Universit Patholog E-mail: g 1526-590 a 2010 b doi:10.10 Abstract: Using the rat... more Received Address Universit Patholog E-mail: g 1526-590 a 2010 b doi:10.10 Abstract: Using the rat chronic constriction injury (CCI) pain model, we evaluated whether nitrous oxide (N2O), a gas shown to have potent anti-hyperalgesic properties, may alleviate neuropathic pain. Mechanical nociceptive threshold was estimated using the paw pressure vocalization test. Thermal allodynia was challenged by measuring the struggle latency by immersion of the hind paw in a 10 C water bath. A single 50% N2O exposure for 1 hour, 15 minutes not only induced potent anti-nociception during N2O exposure but also provoked a delayed and sustained reduction (37% to 46%) of pain hypersensitivity of the injured hind paw and abolished pain hypersensitivity of the contralateral uninjured hind paw for at least 1 month. Thermal allodynia was completely prevented by a single N2O exposure. A preadministration of naltrexone, which markedly reduced acute N2O-induced anti-nociception, did not affect the persistent ...
Medical Gas Research, 2021
The study investigates the perceptions of external auditors and loan officers regarding external ... more The study investigates the perceptions of external auditors and loan officers regarding external auditor's independence in Palestine. Data were gathered using a questionnaire developed by the author and include 5 main issues related to the perception of external auditor's independence. The sampling population identified for this study consists of external auditors working in domestic and international audit firms and financial statement users mainly loan officers in Palestine. The sample included 79 auditors and 76 loan officers. The findings revealed that there are significant differences in the perceptions of external auditors and loan officers in relation to provision of non-audit services, auditor's economic dependence on a single audit client, and long relationship between an auditor and a client. The results revealed mixed results about the effect of presence of active audit committee on independence of the external auditors. Furthermore, acceptance of significant gifts from the client was considered an important factor that may influence auditor independence by loan officers and external auditor and thus significant differences between the two respondent groups were found in relation to acceptance of significant gifts from the client. These findings can be useful to policy makers and professional auditing bodies in Palestine on setting new regulations or strengthening existing ones to enforce auditor's independence in Palestine.
Pain, 2021
Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia ... more Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short duration analgesia in various clinical settings mostly in the form of a N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long lasting analgesic effects related to the blockade of NMDA receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a one hour administration of EMONO or placebo (medical air) on three consecutive days up to one month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to one study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (NPSI), patient global impression of change (PGIC), anxiety, depression and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and seven days after the last administration were not significantly different between the two groups. However, evoked pain intensity (predefined secondary endpoint) and PGIC (exploratory endpoint), were significantly improved in the EMONO group and these effects were maintained up to four weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long term analgesic effects of EMONO in neuropathic pain patients.
Movement disorders : official journal of the Movement Disorder Society, Jan 14, 2018
Parkinson's disease motor symptoms are treated with levodopa, but long-term treatment leads t... more Parkinson's disease motor symptoms are treated with levodopa, but long-term treatment leads to disabling dyskinesia. Altered synaptic transmission and maladaptive plasticity of corticostriatal glutamatergic projections play a critical role in the pathophysiology of dyskinesia. Because the noble gas xenon inhibits excitatory glutamatergic signaling, primarily through allosteric antagonism of the N-methyl-d-aspartate receptors, we aimed to test its putative antidyskinetic capabilities. We first studied the direct effect of xenon gas exposure on corticostriatal plasticity in a murine model of levodopa-induced dyskinesia We then studied the impact of xenon inhalation on behavioral dyskinetic manifestations in the gold-standard rat and primate models of PD and levodopa-induced dyskinesia. Last, we studied the effect of xenon inhalation on axial gait and posture deficits in a primate model of PD with levodopa-induced dyskinesia. This study shows that xenon gas exposure (1) normalized ...
Http Www Theses Fr, 2007
L'objectif de ce travail a consiste a reevaluer les potentialites therapeutiques du protoxyde... more L'objectif de ce travail a consiste a reevaluer les potentialites therapeutiques du protoxyde d'azote (N2O), un gaz utilise depuis plus de 150 ans pour ses proprietes anesthesique et analgesique. Nos resultats montrent que le protoxyde d'azote, probablement en partie via ses proprietes anti-NMDA : i) previent l'amplification de l'hyperalgesie induite par de fortes doses de fentanyl dans un modele de douleur inflammatoire chez le rat, ii) bloque la sensibilisation latente a la douleur mise en evidence a la suite d'une seconde inflammation ou consecutive a l'exposition repetee a des stress (stress environnemental non-nociceptif), iii) previent l'augmentation du niveau d'anxiete induite par de fortes doses de fentanyl, iv) entraine chez le rat neuropathique une reduction de longue duree (semaines) de l'hypersensibilite a la douleur, comparee a l'effet limite (jours) obtenu avec un antagoniste des recepteurs NMDA. Ces donnees precliniques suggerent que, chez l'Homme, l'utilisation en peroperatoire du protoxyde d'azote permettrait d'ameliorer la rehabilitation postoperatoire, non seulement en reduisant l'hyperalgesie postoperatoire, mais egalement en limitant les perturbations psycho-affectives associees. De plus, il pourrait representer une strategie particulierement benefique dans la prise en charge des douleurs neuropathiques, en particulier chez les patients dont les mecanismes centraux de sensibilisation a la douleur predominent.
Pain Research and Management, 2015
BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that... more 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 th...
Douleurs : Evaluation - Diagnostic - Traitement, 2007
Neuroreport, Jan 29, 2010
Rats received an intraplantar carrageenan injection for inducing hind paw inflammation. After 1 h... more Rats received an intraplantar carrageenan injection for inducing hind paw inflammation. After 1 h 45 min, they were exposed to medical air (air group), xenon 25% (Xe-25 group) or 50% (Xe-50 group) for 1 h 45 min. Mechanical nociceptive threshold was evaluated on experimental day and once daily for 1 week. Beyond the well-known antinociceptive effect of xenon, the delayed hyperalgesia observed for 4 days after carrageenan injection was strongly reduced in Xe-25 group and totally suppressed in Xe-50 group on the inflamed hind paw. Moreover, delayed hyperalgesia on the noninflamed hind paw was totally suppressed for both the xenon concentrations. These results show that xenon, beyond its antinociceptive effects, may be a fruitful therapeutic strategy to limit the development of pain sensitization after tissue injury.
Psychoneuroendocrinology, 2009
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright
Pharmacology Biochemistry and Behavior, 2012
Postoperative negative affects such as anxiety need to be better understood and treated to improv... more Postoperative negative affects such as anxiety need to be better understood and treated to improve patient recovery. The present study evaluates the effect of a single exposure to a high-dose of opioid (4×100 μg/kg fentanyl injections in 15 min intervals resulting in a total dose of 400 μg/kg), as used for surgery in humans, on anxiety-like behavior (ALB) in rats. First, the level of anxiety was evaluated 24-h after a high-dose of fentanyl using an elevated plus-maze apparatus. Second, the preventive effect of BN2572, a N-methyl-D-aspartate receptor (NMDA-R) antagonist, and 50% nitrous oxide (N(2)O), a gas with NMDA-R antagonist properties, was assessed. A significant increase in ALB was observed in fentanyl-treated rats. Interestingly, fentanyl-induced ALB was prevented by BN2572, suggesting a NMDA-dependant pathway. Fentanyl-induced ALB was also prevented by a single 50% N(2)O exposure. The present study provides evidence that deleterious outcomes of opioid use, referred to as "post-opioid syndrome", include not only pain hypersensitivity as previously described, but also negative affects such as anxiety. Since N(2)O prevents elements of this post-opioid syndrome, we speculate that N(2)O could be a good therapeutic agent to facilitate postoperative rehabilitation.
The Journal of Pain, 2010
Using the rat chronic constriction injury (CCI) pain model, we evaluated whether nitrous oxide (N... more Using the rat chronic constriction injury (CCI) pain model, we evaluated whether nitrous oxide (N2O), a gas shown to have potent anti-hyperalgesic properties, may alleviate neuropathic pain. Mechanical nociceptive threshold was estimated using the paw pressure vocalization test. Thermal allodynia was challenged by measuring the struggle latency by immersion of the hind paw in a 10 degrees C water bath. A single 50% N2O exposure for 1 hour, 15 minutes not only induced potent anti-nociception during N2O exposure but also provoked a delayed and sustained reduction (37% to 46%) of pain hypersensitivity of the injured hind paw and abolished pain hypersensitivity of the contralateral uninjured hind paw for at least 1 month. Thermal allodynia was completely prevented by a single N2O exposure. A preadministration of naltrexone, which markedly reduced acute N2O-induced anti-nociception, did not affect the persistent reduction of hyperalgesia. The administration of naltrexone in N2O-treated rats, 1 week after the gas exposure, did not induce any effect. This suggests that the long-lasting effect of N2O was not due to its prior acute analgesic effect and was independent of endogenous opioid systems. These data suggest that 50% N2O exposure could be an efficient and safe strategy for alleviating neuropathic pain in a persistent manner. Because a single 50% N2O exposure induced a persistent reduction of hyperalgesia-allodynia in a rat neuropathic pain model, clinical trials must be developed for evaluating the N2O effects in patients with neuropathic pain. The ability of N2O to potentiate analgesic effects of other drugs also must be evaluated.
European Journal of Anaesthesiology, 2006
European Journal of Anaesthesiology, 2010
Background and Goal of Study: In a recent retrospective clinical study, we found an association b... more Background and Goal of Study: In a recent retrospective clinical study, we found an association between anaesthetic technique during breast cancer surgery and recurrence or metastases [1]. While anaesthetic technique is reported to affect perioperative immune function, there is little known about direct effects of anaesthetic agents on cancer cells [2,3]. Therefore, we investigated the effect of sevoflurane on breast cancer cell functions that contribute to its metastatic potential (proliferation, migration and invasion) using two different breast cancer cell lines. Materials and Methods: MCF7 is an ER+ breast cancer cell line while MDA-MB-231 is ER-and clinically more aggressive. Cells were incubated with or without sevoflurane in concentrations of 1, 2, 3, and 4 mM for 6 hrs, corresponding to clinically relevant concentrations and exposure times. Cell proliferation was determined using CellTiter 96 Aqueous One Solution Cell Proliferation Assay (Promega Inc.). Cell migration was determined by scratch method. Cell invasion was determined by BD Biocoat Matrigen Invasion Assay (BD Biosciences). Results were compared using independent sample t test for differences between groups. Results and Discussion: Sevoflurane decreased proliferation by 37-100% in MCF7 cells and increased it by 5-26% in MDA-MB-231 (P<0.05). It increased migration by 58% in MCF7 (P=0.04) and by 63% in MDA-MB-231 (P=0.03). Invasion was also increased by sevoflurane; 29-47% in MCF7 (P=0.02) and 9-24% in MDA-MB-231, (P=0.04). Results on effect of sevoflurane on proliferation of MCF7 cells are consistent with previous studies, but in MDA-MB-231 cell line sevoflurane actually stimulated proliferation. This stimulating effect was then evident in both cell lines' migration and invasion. Although these functions are based on different mechanisms, they all contribute to metastatic potential of cancer cells and we can conclude that sevoflurane stimulates it. Differences between effect on proliferation of both cell lines could be explained by difference in differentiation between cell lines and by different mechanisms employed, all of which still needs to be investigated. Conclusion(s): Our data is consistent with the hypothesis that anaesthesia for cancer surgery may facilitate conditions conducive to propagation or resistance of metastases, probably also by directly affecting cancer cells' function. References:
Alcoholism: Clinical and Experimental Research, 2013
Background: In recent years, the glutamate theory of alcoholism has emerged as a major theory in ... more Background: In recent years, the glutamate theory of alcoholism has emerged as a major theory in the addiction research field and N-methyl-D-aspartate (NMDA) receptors have been shown to play a major role in alcohol craving and relapse. The NMDA receptors are considered as the primary side of action of the anesthetic gases xenon (Xe) and nitrous oxide (N 2 O). Despite the rapid on/off kinetics of these gases on the NMDA receptor, a brief gas exposure can induce an analgesic or antireward effect lasting several days. The aim of this study was to examine the effect of both Xe and N 2 O on alcoholseeking and relapse-like drinking behavior (measured as the alcohol deprivation effect) in Wistar rats. Methods: We used 2 standard procedures-the alcohol deprivation model with repeated deprivation phases and the cue-induced reinstatement model of alcohol seeking-to study the effect of 2 brief gas exposures of either Xe, N 2 O, or control gas on relapse-like drinking and alcohol-seeking behavior. Results: Here, we show that exposure to Xe during the last 24 hours of abstinence produced a trend toward reduced ethanol intake during the first alcohol re-exposure days. In addition, Xe gas exposure significantly decreased the cue-induced reinstatement of alcohol-seeking behavior. N 2 O had no effect on either behavior. Conclusions: Xe reduces alcohol-seeking behavior in rats and may therefore also interfere with craving in human alcoholics.
Neuropharmacology, 2007
Improving rehabilitation after a severe tissue injury does not only require a reduction in pain, ... more Improving rehabilitation after a severe tissue injury does not only require a reduction in pain, but also requires alleviation of negative affects, particularly anxiety. Although opioids remain unsurpassed analgesics to relieve moderate to severe pain, it has been shown that they also induce latent pain sensitization leading to long-lasting hyperalgesia via N-methyl-D-aspartate-(NMDA)-dependent pronociceptive systems. The present study evaluated the ability of nitrous oxide (N2O), a gas with NMDA antagonist properties, to prevent latent pain sensitization and long-term anxiety-like behavior (ALB) in rats with pain and opioid experiences. On D0, the pro-inflammatory drug carrageenan was injected in one hind paw of rats treated with fentanyl (4x100 microg/kg subcutaneously). Nociceptive threshold was evaluated with the paw pressure vocalization test. Rats were re-exposed to carrageenan or exposed to repeated non-nociceptive environmental stress (NNES) 2-3 weeks later. Rats were also challenged in the elevated plus-maze 2 weeks after fentanyl administration for evaluating ALB. The preventive effects of a single 4 h 50/50% N2O-O2 exposure performed on D0 was evaluated. Fifty percent N2O strongly reduced hyperalgesia induced by a first inflammation and its enhancement by fentanyl, and prevented exaggerated hyperalgesia induced by second inflammatory pain or NNES. Moreover, we provide first evidence that a high fentanyl dose induces long-term ALB 2 weeks after its administration. When associated with fentanyl, 50% N2O prevented such long-term ALB. These results suggest that a single exposure to N2O could improve post-injury pain management and facilitate rehabilitation especially when potent analgesics as opioids have to be used.
Neuropharmacology, 2007
Improving rehabilitation after a severe tissue injury does not only require a reduction in pain, ... more Improving rehabilitation after a severe tissue injury does not only require a reduction in pain, but also requires alleviation of negative affects, particularly anxiety. Although opioids remain unsurpassed analgesics to relieve moderate to severe pain, it has been shown that they also induce latent pain sensitization leading to long-lasting hyperalgesia via N-methyl-D-aspartate-(NMDA)-dependent pronociceptive systems. The present study evaluated the ability of nitrous oxide (N2O), a gas with NMDA antagonist properties, to prevent latent pain sensitization and long-term anxiety-like behavior (ALB) in rats with pain and opioid experiences. On D0, the pro-inflammatory drug carrageenan was injected in one hind paw of rats treated with fentanyl (4x100 microg/kg subcutaneously). Nociceptive threshold was evaluated with the paw pressure vocalization test. Rats were re-exposed to carrageenan or exposed to repeated non-nociceptive environmental stress (NNES) 2-3 weeks later. Rats were also challenged in the elevated plus-maze 2 weeks after fentanyl administration for evaluating ALB. The preventive effects of a single 4 h 50/50% N2O-O2 exposure performed on D0 was evaluated. Fifty percent N2O strongly reduced hyperalgesia induced by a first inflammation and its enhancement by fentanyl, and prevented exaggerated hyperalgesia induced by second inflammatory pain or NNES. Moreover, we provide first evidence that a high fentanyl dose induces long-term ALB 2 weeks after its administration. When associated with fentanyl, 50% N2O prevented such long-term ALB. These results suggest that a single exposure to N2O could improve post-injury pain management and facilitate rehabilitation especially when potent analgesics as opioids have to be used.
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Papers by Baptiste Bessière