Long-term use of opioids is hindered by respiratory depression and the possibility for fatal overdose in drug abusers. This is attributed to higher levels of tolerance that develops against antinociception than to respiratory depression. Identifying important mechanisms that would increase morphine respiratory depression and overdose tolerance could lead to the safer use of opioids. Because pro...

BACKGROUND Increasing evidence suggests that microRNAs are functionally involved in the initiation and maintenance of pain hypersensitivity, including chronic morphine analgesic tolerance, through the posttranscriptional regulation of pain-related genes. We have previously demonstrated that miR-219 regulates inflammatory pain in the spinal cord by targeting calcium/calmodulin-dependent protein ...

Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine...

BACKGROUND Sevoflurane is a rapid-acting volatile anaesthetic agent frequently used in paediatric anaesthesia despite transient postoperative symptoms of cerebral excitation, particularly in preschool children. This randomised and investigator-blinded study was designed to evaluate whether premedication with an opioid might reduce non-divertible postoperative excitation more than premedication ...

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at res...

BACKGROUND Opioid maintenance treatment is the option of choice to stabilize opioid-dependent patients. Whilst efficacy of methadone and buprenorphine has been studied extensively, fewer data on slow-release oral morphine are available. AIMS This study analyzes the effects of slow-release oral morphine compared to methadone with regard to self-reported mental symptoms, drug use and satisfacti...

Morphine is one of the most potent analgesic drugs. However, the utility of morphine in the management of chronic pain is limited by its rapid development of tolerance. Morphine exerts all of its pharmacological effects via the μ-opioid receptor. In many systems, tolerance is associated with phosphorylation and desensitization of G-protein-coupled receptors (GPCRs). In case of the μ-opioid rece...

Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance,...

Acute pain management in opioid dependent patients remains a challenging and complex problem and it is becoming more common (1). In the acute pain setting, in addition to their daily opioid maintenance these patients need a multimodal approach (1). Imani et al. in their study have shown that instead of simply increasing the dosage of morphine, using morphine in addition to chlorpromazine, prome...