目的观察不同剂量咪达唑仑对氯胺酮镇痛效应的影响,为临床合理配伍使用药物提供依据。方法腹腔注射25 mg/kg氯胺酮建立镇痛模型,150只小鼠均分为NS组、M组、K组、M1K组和M2K组,采用甩尾法、热板法和扭体法(n=10)分别观察腹腔注射1、2 mg...目的观察不同剂量咪达唑仑对氯胺酮镇痛效应的影响,为临床合理配伍使用药物提供依据。方法腹腔注射25 mg/kg氯胺酮建立镇痛模型,150只小鼠均分为NS组、M组、K组、M1K组和M2K组,采用甩尾法、热板法和扭体法(n=10)分别观察腹腔注射1、2 mg/kg咪达唑仑对氯胺酮镇痛小鼠甩尾潜伏期(TFL)、热板法痛阈(HPPT)和扭体次数(WTs)的影响。结果给药后5、10、15、20 min K组TEL、HPPT延长(P<0.05);各时点M组小鼠TFL、HPPT均无明显变化;M1K组和M2K组给药后10、15、20 min TFL、HPPT延长,给药后15 min M1K组和M2K组TEL、HPPT明显长于K组(P<0.05或P<0.01)。给药后15 min内K、M1K和M2K组小鼠WTs明显少于NS组(P<0.01)。但K、M1K和M2K组间差异无统计学意义(P<0.05或P<0.01)。结论一定剂量的咪达唑仑可以增强氯胺酮的体表镇痛作用。展开更多
Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs （...Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs （NSAIDs）, or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic （intraperitoneal） administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.展开更多
Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a...Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia,where two different contexts(dark and bright) were matched with a high(52°C) or low(48°C) temperature in the hot-plate test during training. Before and after training,we set the temperature to the high level in both contexts.Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone(an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.展开更多
文摘目的观察不同剂量咪达唑仑对氯胺酮镇痛效应的影响,为临床合理配伍使用药物提供依据。方法腹腔注射25 mg/kg氯胺酮建立镇痛模型,150只小鼠均分为NS组、M组、K组、M1K组和M2K组,采用甩尾法、热板法和扭体法(n=10)分别观察腹腔注射1、2 mg/kg咪达唑仑对氯胺酮镇痛小鼠甩尾潜伏期(TFL)、热板法痛阈(HPPT)和扭体次数(WTs)的影响。结果给药后5、10、15、20 min K组TEL、HPPT延长(P<0.05);各时点M组小鼠TFL、HPPT均无明显变化;M1K组和M2K组给药后10、15、20 min TFL、HPPT延长,给药后15 min M1K组和M2K组TEL、HPPT明显长于K组(P<0.05或P<0.01)。给药后15 min内K、M1K和M2K组小鼠WTs明显少于NS组(P<0.01)。但K、M1K和M2K组间差异无统计学意义(P<0.05或P<0.01)。结论一定剂量的咪达唑仑可以增强氯胺酮的体表镇痛作用。
基金supported by the grant from Georgian National Science Foundation,No.GNSF/ST07/6-234
文摘Pain is a sensation related to potential or actual damage in some tissue of the body. The mainstay of medical pain therapy remains drugs that have been around for decades, like non-steroidal anti-inflammatory drugs （NSAIDs）, or opiates. However, adverse effects of opiates, particularly tolerance, limit their clinical use. Several lines of investigations have shown that systemic （intraperitoneal） administration of NSAIDs induces antinociception with some effects of tolerance. In this review, we report that repeated microinjection of NSAIDs analgin, clodifen, ketorolac and xefocam into the central nucleus of amygdala, the midbrain periaqueductal grey matter and nucleus raphe magnus in the following 4 days result in progressively less antinociception compared to the saline control testing in the tail-flick reflex and hot plate latency tests. Hence, tolerance develops to these drugs and cross-tolerance to morphine in male rats. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, the periaqueductal grey-rostral ventro-medial part of medulla circuit should be viewed as a pain-modulation system. These data are important for human medicine. In particular, cross-tolerance between non-opioid and opioid analgesics should be important in the clinical setting.
基金supported by grants from the National Natural Science Foundation of China (91732107, 31200835, 81571067, and 81521063)the National Basic Research Development Program (973 Program) of China (2014CB548200 and 2015CB554503)
文摘Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia,where two different contexts(dark and bright) were matched with a high(52°C) or low(48°C) temperature in the hot-plate test during training. Before and after training,we set the temperature to the high level in both contexts.Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone(an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.
