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The main side effects of opioid use are physiological and psychological dependence. The transient receptor potential channels, including transient receptor potential ankyrin 1 (TRPA1), are involved in various neurological disorders. We aimed to evaluate the effect of TRPA1 inhibition on morphine-induced conditioned place preference (CPP) and physical dependence. For induction of CPP, morphine (10 and 20 mg/kg) was administrated for four consecutive days to male BALB/c mice. The effects of HC030031 (TRPA1 antagonist, 10, 25, and 50 mg/kg) on the expression and reinstatement of morphine-induced CPP were evaluated. For induction of physical dependence, morphine was injected three times a day for 3 days. Withdrawal-related behaviors such as jumping and defecation were precipitated by the administration of naloxone to morphine-dependent mice. The effect of HC030031 on jumping and defecation was assessed. The results showed that 20 mg/kg of morphine elicited a significant CPP. HC030031 reduced the expression of morphine CPP without any change in the locomotor activity. It also decreased the reinstatement of morphine CPP. HC030031 mitigated morphine withdrawal via reducing jumping and defecation. The present study demonstrated that HC030031 decreased morphine-associated CPP and physical dependence. It is presumed that TRPA1 has interaction with the main pharmacological effects of morphine. Keywords: morphine, opiate dependence, TRPA1, reward, conditioned place preference, HC030031 La dependance physiologique et psychologique sont les principaux effets indesirables de l'utilisation des opiaces. Les canaux TRP (pour << transient receptor potential >>), y compris TRPA1, jouent un role dans divers troubles neurologiques. Nous visions a evaluer l'effet de l'inhibition de TRPA1 sur la preference de place conditionnee (CPP pour << conditioned place preference >>) et la dependance physique engendrees par la morphine. En vue de produire la CPP, nous avons administre de la morphine (a 10 et 20 mg/kg) a des souris BALB/c males pendant quatre jours consecutifs. Nous avons evalue les effets du HC030031 (antagoniste de TRPA1, a 10, 25 et 50 mg/kg) sur l'expression et la reinstauration de la CPP engendree par la morphine. En vue de provoquer une dependance physique, nous avons injecte de la morphine trois fois par jour pendant trois jours. Les comportements lies au retrait comme le saut et la defecation etaient precipites par l'administration de naloxone a des souris dependantes de la morphine. Nous avons evalue les effets du HC030031 sur le saut et la defecation. Les resultats ont montre que la morphine a 20 mg/kg entrainait une CPP marquee. Le HC030031 entrainait une diminution de l'expression de la CPP liee a la morphine sans aucune modification de l'activite locomotrice. Il entrainait aussi la reinstauration de la CPP liee a la morphine. Avec une diminution du saut et de la defecation, le HC030031 entrainait une attenuation du retrait de la morphine. La presente etude a montre que le HC030031 entrainait une diminution de la CPP et de la dependance physique liees a la morphine. Nous presumons qu'il existe une interaction entre TRPA1 et les principaux effets pharmacologiques de la morphine. [Traduit par la Redaction] Mots-cles : morphine, dependance aux opiaces, TRPA1, recompense, preference de place conditionnee, HC030031, Introduction Morphine and other opioids are the primary therapeutic medicines for controlling moderate and severe pains (Lutz and Kieffer 2013). Despite well-known analgesic properties, their use is limited by various [...]

Objective The growing opioid crisis increasingly affects maternal care in the US and it is unknown if opioid use puts pregnant women at increased odds for cesarean delivery (CD). Understanding how opioids influence CD trends is important in improving maternal and neonatal outcomes. This study aims to understand the association of opioid use with CD in the context of the demographic, clinical, behavioral, and health system complexity. Methods This retrospective cross-sectional analysis used representative data from the 2012-2014 National Inpatient Sample. Opioid use during pregnancy, CD, and other clinical variables were identified using ICD9 codes. Characteristics were assessed using bivariate and multivariate statistics. A logistic regression model was used to determine the association between opioid use and CD while controlling for confounders. Adjustments were made for rural/urban hospital location, regional median income, maternal age, race, and medical and pregnancy-related conditions. Results The rate of CD in the overall sample was about 30%. Among opioids-users, the overall proportion of CD was significantly less (24.7%). The adjusted odds ratio for CD among opioids users was 0.74 (CI: 0.73-0.76, p < 0.001). This finding is unique to pregnant women who are covered by public insurance. In rural areas, the relationship between opioid use and CD was not significant. Conclusion Opioid use during pregnancy is associated with lower CD rates in urban settings. This evidence suggests that maternal care varies between rural and urban areas in relation to CD of pregnant opioid users compared to non-opioid users., Author(s): Carolyn Knoll [sup.1] , Beri Massa-Buck [sup.2] , Dinan Abdelatif [sup.2] , Amr Madkour [sup.3] , Mohamed Mohamed [sup.2] [sup.3] [sup.4] Author Affiliations: (1) grid.253615.6, 0000 0004 1936 9510, [...]

Opioid-induced hyperalgesia (OIH) is a state of paradoxically enhanced pain transmission, termed nociceptive sensitization, described to occur in both humans and animals after repeated administration of opioid drugs, including rapidly acting remifentanil. However, molecular mechanisms of OIH remain understudied. In this issue of the JCI, Yan Jin and colleagues provided strong evidence that hyperexcitable thalamocortical networks drive remifentanil-induced hyperalgesia in a rodent model of postsurgical pain. Furthermore, the authors specifically identified an important role of the CaV3.1 isoform of low-voltage-activated or T-type calcium channels (T-channels) in this process. Further experiments are needed to determine whether thalamic T channels could serve as targets for the treatment of OIH., Opioid-induced hyperalgesia The use of opioids in operating rooms and clinics has steadily increased over the last decades, making this drug class one of the most commonly prescribed in the [...]

Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics. Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns. Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management. The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol. More countries have decided to legalise the medicinal use of cannabis and marijuana. Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications. The pharmacokinetics and safety of medical cannabis need to be studied by conducting clinical research. The complex and variable chemically active contents of herbal cannabis and methodological limitations in the administration of cannabis to study participants, make the clinical research difficult., Author(s): Mari Kannan Maharajan [sup.1], Yu Jing Yong [sup.2], Hong Yang Yip [sup.2], Sze Shee Woon [sup.2], Kar Mon Yeap [sup.2], Khai Yeng Yap [sup.2], Shuen Chi Yip [sup.2], Kai [...]

Opioid use during pregnancy is associated with suboptimal pregnancy outcomes. Little is known about child neurodevelopmental outcomes. We examined associations between maternal opioid prescriptions preconception to delivery (peri-pregnancy) and child's risk of ASD, developmental delay/disorder (DD) with no ASD features, or ASD/DD with autism features in the Study to Explore Early Development, a case-control study of neurodevelopment. Preconception opioid prescription was associated with 2.43 times the odds of ASD [95% confidence interval (CI) 0.99, 6.02] and 2.64 times the odds of ASD/DD with autism features (95% CI 1.10, 6.31) compared to mothers without prescriptions. Odds for ASD and ASD/DD were non-significantly elevated for first trimester prescriptions. Work exploring mechanisms and timing between peri-pregnancy opioid use and child neurodevelopment is needed., Author(s): Eric Rubenstein [sup.1] , Jessica C. Young [sup.2] , Lisa A. Croen [sup.3] , Carolyn DiGuiseppi [sup.4] , Nicole F. Dowling [sup.5] , Li-Ching Lee [sup.6] , Laura Schieve [...]