The effect of cyclooxygenase-2 inhibition on pentylenetetrazole-induced seizure threshold in mice

Background: Previous studies have shown the protective effect of cyclooxygenase (COX) enzyme in development of convulsions. However, involvement of COX-2 in the pathogenesis of epilepsy is not yet well-known. The present study was designed to investigate the effect of celecoxib and nimesulide (selective COX-2 inhibitors) on pentylenetetrazole (PTZ)-induced clonic seizure threshold in mice. Materials and Methods: In this study, white male mice were randomly divided into 13 groups including control groups, solvent (Tween 80) and eleven experimental groups which received celecoxib (2.5, 5 and 10 mg/kg), nimesulide (2.5, 5 and 10 mg/kg), diazepam (0.1, 0.5 and 5 mg/kg), and combination of non-effective dose of diazepam with celecoxib or nimesulide. Pentylenetetrazol-induced clonic seizure threshold was assessed in all groups. Results: Nimesulide (2.5 and 5 mg/kg), celecoxib (2.5 and 5 mg/kg), and diazepam (0.5 and 5 mg/kg) significantly increased the PTZ-induced seizure threshold compared with the solvent group (P<0.05). Also, only combination of sub-effective dose of diazepam (0.1 mg/kg) with celecoxib (2.5 mg/kg) showed a significant protective effect against PTZ-induced seizure threshold (P<0.01). Conclusion: Findings of the current study show the possible role of COX-2 isoenzyme in the pathophysiology of epilepsy. It is possible that some COX-2 inhibitors such as celecoxib act through GABAergic neurons and reduce excitability by increasing GABA release. Also, the difference between the effects of celecoxib and nimesulide can be attributed to the effect of these two compounds on COX-1 and COX-2 expression

The survey of pattern of abusing and causes of addiction tendency among women undergoing methadone maintenance treatment in Kashan city during 2017-2018

Background: The current prevalence rates indicate an increasing trend of substance abuse among women. This study aimed at determining the pattern of consumption and causative factors for tendency to drug abuse in woman referred to addiction treatment centers. Materials and Methods: In this descriptive cross-sectional study, the study population was all women referred to addiction treatment centers of Kashan during 2017-2018. The research instrument was a demographic information questionnaire, causes of drug abuse tendency and structured clinical interviews with the Diagnostic and Statistical Manual of Psychiatric Disorders (SCID) to assess the substance abuse disorder. Results: The mean age and onset age of drug abuse were 40±10.3 and 25±6.4 years, respectively. Opium was the most common abused drug (81) and smoking was the most cited method for drug abuse. Ten percent of the patients had a history of injection. The main causes of drug tendency from the perspective of the patients were addict family (77), easy access to drugs (64), as well as depression and disappointment (56). Conclusion: The pattern of drug abuse among women undergoing the method one maintenance treatment in Kashan is traditional on the basis of the opium derivatives. The addict family was the main cause of drug abuse. Therefore, it would be necessary to pay more attention to the family of the patients as vulnerable groups in planning and to provide training on the causes of drug abuse tendency and preventive measures

Experiencing neonatal maternal separation increased pain sensitivity in adult male mice: Involvement of oxytocinergic system

Early-life stress adversely affects the development of the brain, and alters a variety of behaviors such as pain in later life. In present study, we investigated how early-life stress (maternal separation or MS) can affect the nociceptive response later in life. We particularly focused on the role of oxytocin (OT) in regulating nociception in previously exposed (MS during early postnatal development) mice that were subjected to acute stress (restraint stress or RS). Further, we evaluated whether such modulation of pain sensation in MS mice are regulated by shared mechanisms of the OTergic and opioidergic systems. To do this, we assessed the underlying systems mediating the nociceptive response by administrating different antagonists (for both opioid and OTergic systems) under the different experimental conditions (control vs MS, and control plus RS vs MS plus RS). Our results showed that MS increased pain sensitivity in both tail-flick and hot-plate tests while after administration of OT (1 μg/μl/mouse, i.c.v) pain threshold was increased. Atosiban, an OT antagonist (10 μg/μl/mouse, i.c.v) abolished the effects of OT. While acute RS increased the pain threshold in control (and not MS) mice, treating MS mice with OT normalized the pain response to RS. This latter effect was reversed by atosiban and/or naltrexone, an opioid antagonist (0.5 μg/μl/mouse, i.c.v) suggesting that OT enhances the effect of endogenous opioids. OTergic system is involved in mediating the nociception under acute stress in mice subjected to early-life stress and OTergic and opioidergic systems interact to modulate pain sensitivity in MS mic

Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

Objective(s): Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP) was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO) did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO) administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine