Background Preconditioning with repeated electroacupuncture （EA） could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu（μ）-, d...Background Preconditioning with repeated electroacupuncture （EA） could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu（μ）-, delta（δ）- or kappa（κ）-opioid receptors are involved in the neuroprotecUon induced by repeated EA preconditioning. Methods The rats were pretreated with naltrindole （NTI）, nor-binaltorphimine （nor-BNI） or D-Phe-Cys-Tyr-D- Trp-Om-Thr-Pen-Thr-NH2 （CTOP）, which is a highly selective δ-, κ- or μ-opioid receptor antagonist respectively, before each EA preconditioning （30 minutes per day, 5 days）. Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion （MCAO） was induced for 120 minutes. The brain infarct volume was determined with 2,3,5-tdphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats. Results The EA preconditioning reduced brain infarct volume compared with the control rats （P=-0.000）. Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats （P〈0.001）. But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats （P=-0.000）. The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats （P=-0.000）. Conclusion Repeated EA preconditioning stimulates the release of enkephalins, which may bind 5- and p-opioid receptors to induce the tolerance against focal cerebral ischemia.展开更多
Background Opioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown.The μ-opioid receptor （MOR） has an important ...Background Opioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown.The μ-opioid receptor （MOR） has an important role in mediating the actions of morphine and other analgesic agents.This study is aimed at exploring the changes of MOR in the periaqueductal gray （PAG） in rats when morphine is substituted for equianalgesic fentanyl.Methods Forty rats were randomly assigned to five treatment groups：7 days normal saline group （N group）,7 days fentanyl group （F group）,7 days morphine group （M group）,7 days morphine and 7 days fentanyl-switching group （MF group）,and 14 days morphine group （MM group）.Rats repeatedly received subcutaneous injections of morphine sulfate （10 mg/kg） or equianalgesic fentanyl sulfate （0.1 mg/kg） twice daily.Rats＇ antinociceptive response to thermal pain was evaluated by the tail flick latency assay.MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.Results This study showed that after morphine was substituted with fentanyl on day 8,the tail flick latency （TFL） increased from （3.9±0.4） seconds to （11.4±0.4） seconds.The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group （P〈0.05） but more than that in MM group （P〈0.05）.Conclusions Equianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance,which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.展开更多
The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitator...The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitatory autonomic withdrawal effects in chronic opioid-dependent animals and humans, as well as to the “quasi-morphine withdrawal syndrome” evoked in naive rodents shortly after acute systemic injection of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors. These symptoms result from excessive excitatory opioid receptor signaling and increased endorphin release. Pharmacologic analyses of the remarkably plastic bimodal (excitatory/inhibitory) signaling functions of opioid receptors have utilized microelectrode recordings from opioid-sensitive neurons in tissue cultures of mouse sensory ganglia and hot-water tail-flick assays in mice. These studies led to development of specific chemical formulations that switch opioid receptor signaling from an excessively excitatory to a normal inhibitory mode. Critical combinations of cAMP-PDE inhibitors that release endorphins plus specific agents that switch opioid receptors from excitatory Gs-coupled to inhibitory Gi/Go-coupled signaling were shown to attenuate hyperalgesia and distress evoked by diverse chemical stressors in mouse tail-flick assays. Both the “quasi-morphine withdrawal syndrome” in naive rodents as well as the excitatory withdrawal effects in chronic, opioid-dependent animals and humans may be manifestations of a common Endorphinergic Distress Syndrome (EDS). We suggest that many distress symptoms are caused by EDS, a dysfunctional imbalance in the endogenous opioid system, consisting of abnormal endorphin levels, together with opioid receptors predominately in their excitatory mode. Therefore, concomitantly enhancing endogenous opioid release and switching excessive excitatory opioid receptor signaling to inhibitory signaling can attenuate these distress symptoms. Trials of a critically formulated oral preparation, containing both endorphin en展开更多
Objective： To observe the adjuvant analgesic efficacy of Han＇s Acupoint Nerve Stimulator （HANS） in opioid tolerant patients with cancer pain. Methods： A prospective non-controlled study was conducted. Opioid tole...Objective： To observe the adjuvant analgesic efficacy of Han＇s Acupoint Nerve Stimulator （HANS） in opioid tolerant patients with cancer pain. Methods： A prospective non-controlled study was conducted. Opioid tolerant patients with cancer pain were enrolled and treated with both routinely analgesics and adjuvant HANS （2/100 Hz for 30 min/d, 5 d on and 2 d off for two weeks）. Cancer pain, quality of life （QOL）, anxiety and depression were assessed before enrollment and on d 8 and d 15 with the BPI-C, EORTC QLQ-C30, and self-rating anxiety scale （SAS）/ self-rating depression scale （SDS）, respectively; the therapeutic frequency of breakthrough pain （BP） and daily opioid dose were also recorded. Results： Totally 47 patients meeting the inclusion criteria participated in this study; 43 patients completed the two-week treatment and assessment. The mean scores of patient＇s ＂worst＂ and ＂least＂ pain intensity assessed with BPI-C decreased significantly on d 8 and d 15; the therapeutic frequency of BP also significantly decreased; but the average daily dose of opioids did not change significantly. For the nine symptoms in EORTC QLQ-C30 assessment, the mean scores of pain, fatigue, constipation and insomnia were significantly lower on d 8 and d 15 compared with baseline; the mean scores of the overall health status, nausea/vomiting and the incidence rates of both anxiety and depression also decreased significantly on d 15. Conclusions： To opioid tolerant patients with cancer pain, adjuvant treatment with HANS could improve pain release and patients＇ QOL by decreasing the severity of pain, fatigue, constipation, insomnia and other concomitant symptoms; it could also decrease the incidence rates of anxiety and depression.展开更多
基金the National Natural Science Foundation of China(No.30471664).
文摘Background Preconditioning with repeated electroacupuncture （EA） could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu（μ）-, delta（δ）- or kappa（κ）-opioid receptors are involved in the neuroprotecUon induced by repeated EA preconditioning. Methods The rats were pretreated with naltrindole （NTI）, nor-binaltorphimine （nor-BNI） or D-Phe-Cys-Tyr-D- Trp-Om-Thr-Pen-Thr-NH2 （CTOP）, which is a highly selective δ-, κ- or μ-opioid receptor antagonist respectively, before each EA preconditioning （30 minutes per day, 5 days）. Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion （MCAO） was induced for 120 minutes. The brain infarct volume was determined with 2,3,5-tdphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats. Results The EA preconditioning reduced brain infarct volume compared with the control rats （P=-0.000）. Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats （P〈0.001）. But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats （P=-0.000）. The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats （P=-0.000）. Conclusion Repeated EA preconditioning stimulates the release of enkephalins, which may bind 5- and p-opioid receptors to induce the tolerance against focal cerebral ischemia.
文摘Background Opioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown.The μ-opioid receptor （MOR） has an important role in mediating the actions of morphine and other analgesic agents.This study is aimed at exploring the changes of MOR in the periaqueductal gray （PAG） in rats when morphine is substituted for equianalgesic fentanyl.Methods Forty rats were randomly assigned to five treatment groups：7 days normal saline group （N group）,7 days fentanyl group （F group）,7 days morphine group （M group）,7 days morphine and 7 days fentanyl-switching group （MF group）,and 14 days morphine group （MM group）.Rats repeatedly received subcutaneous injections of morphine sulfate （10 mg/kg） or equianalgesic fentanyl sulfate （0.1 mg/kg） twice daily.Rats＇ antinociceptive response to thermal pain was evaluated by the tail flick latency assay.MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.Results This study showed that after morphine was substituted with fentanyl on day 8,the tail flick latency （TFL） increased from （3.9±0.4） seconds to （11.4±0.4） seconds.The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group （P〈0.05） but more than that in MM group （P〈0.05）.Conclusions Equianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance,which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.
文摘The endogenous opioid system plays a significant role in the modulation of distress in many psychiatric, neurologic, and neurodevelopmental disorders. Many clinical distress symptoms show similarities to the excitatory autonomic withdrawal effects in chronic opioid-dependent animals and humans, as well as to the “quasi-morphine withdrawal syndrome” evoked in naive rodents shortly after acute systemic injection of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors. These symptoms result from excessive excitatory opioid receptor signaling and increased endorphin release. Pharmacologic analyses of the remarkably plastic bimodal (excitatory/inhibitory) signaling functions of opioid receptors have utilized microelectrode recordings from opioid-sensitive neurons in tissue cultures of mouse sensory ganglia and hot-water tail-flick assays in mice. These studies led to development of specific chemical formulations that switch opioid receptor signaling from an excessively excitatory to a normal inhibitory mode. Critical combinations of cAMP-PDE inhibitors that release endorphins plus specific agents that switch opioid receptors from excitatory Gs-coupled to inhibitory Gi/Go-coupled signaling were shown to attenuate hyperalgesia and distress evoked by diverse chemical stressors in mouse tail-flick assays. Both the “quasi-morphine withdrawal syndrome” in naive rodents as well as the excitatory withdrawal effects in chronic, opioid-dependent animals and humans may be manifestations of a common Endorphinergic Distress Syndrome (EDS). We suggest that many distress symptoms are caused by EDS, a dysfunctional imbalance in the endogenous opioid system, consisting of abnormal endorphin levels, together with opioid receptors predominately in their excitatory mode. Therefore, concomitantly enhancing endogenous opioid release and switching excessive excitatory opioid receptor signaling to inhibitory signaling can attenuate these distress symptoms. Trials of a critically formulated oral preparation, containing both endorphin en
文摘Objective： To observe the adjuvant analgesic efficacy of Han＇s Acupoint Nerve Stimulator （HANS） in opioid tolerant patients with cancer pain. Methods： A prospective non-controlled study was conducted. Opioid tolerant patients with cancer pain were enrolled and treated with both routinely analgesics and adjuvant HANS （2/100 Hz for 30 min/d, 5 d on and 2 d off for two weeks）. Cancer pain, quality of life （QOL）, anxiety and depression were assessed before enrollment and on d 8 and d 15 with the BPI-C, EORTC QLQ-C30, and self-rating anxiety scale （SAS）/ self-rating depression scale （SDS）, respectively; the therapeutic frequency of breakthrough pain （BP） and daily opioid dose were also recorded. Results： Totally 47 patients meeting the inclusion criteria participated in this study; 43 patients completed the two-week treatment and assessment. The mean scores of patient＇s ＂worst＂ and ＂least＂ pain intensity assessed with BPI-C decreased significantly on d 8 and d 15; the therapeutic frequency of BP also significantly decreased; but the average daily dose of opioids did not change significantly. For the nine symptoms in EORTC QLQ-C30 assessment, the mean scores of pain, fatigue, constipation and insomnia were significantly lower on d 8 and d 15 compared with baseline; the mean scores of the overall health status, nausea/vomiting and the incidence rates of both anxiety and depression also decreased significantly on d 15. Conclusions： To opioid tolerant patients with cancer pain, adjuvant treatment with HANS could improve pain release and patients＇ QOL by decreasing the severity of pain, fatigue, constipation, insomnia and other concomitant symptoms; it could also decrease the incidence rates of anxiety and depression.
