Clonidine antinociceptive activity: Effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat

Summary Clonidine is able to increase the threshold for vocalisation during stimulation and the threshold for vocalisation after withdrawal of stimulus (vocalisation afterdischarge). These effects of clonidine were investigated after treatment of rats with drugs influencing central monoaminergic and cholinergic mechanisms.Chlorpromazine, atropine and p-chlorophenyl-alanine increased the activity of clonidine at both thresholds while phenoxybenzamine and reserpine pretreatment increased the activity at the threshold for vocalisation only.Yohimbine decreased clonidine activity at both thresholds while 5-HTP and -methyl-p-tyrosine decreased the effects at the threshold for vocalisation afterdischarge. Naloxone did not change the activity of clonidine at either pain response studied.It is concluded from the present findings that influence from several neuronal systems modulate the antinociceptive action of clonidine.The inhibition of the medullary nociceptive response after clonidine might be connected to a decreased activity of noradrenergic neurons. Endogenous noradrenaline seems to be of minor importance in mediating this effect. It is moreover shown that decreased cholinergic receptor activity enhances clonidine antinociceptive action on both medullary and diencephalic-rhinencephalic pain responses. The possible involvement of serotonin in these functional responses after clonidine is also discussed.Data from this investigation was presented at the International Narcotic Research Club Conference, Airlie, Va. 1975.     

Reduction of stress-induced analgesia but not of exogenous opioid effects in mice lacking CB1 receptors

CB1 cannabinoid receptors are widely distributed in the central nervous system where they mediate most of the cannabinoid-induced responses. Here we have evaluated the interactions between the CB1 cannabinoid receptors and the endogenous opioid system by assaying a number of well-characterized opioid responses, e.g. antinociception and stress-mediated effects, on mutant mice in which the CB1 receptor gene was invalidated. The spontaneous responses to various nociceptive stimuli (thermal, mechanical and visceral pain) were not changed in mutant CB1 mice. Furthermore, the absence of the CB1 cannabinoid receptor did not modify the antinociceptive effects induced by different opioid agonists: morphine (preferential mu opioid agonist), D-Pen2-D-Pen5-enkephalin (DPDPE) and deltorphin II (selective delta opioid agonists), and U-50,488H (selective kappa opioid agonist) in the hot-plate and tail-immersion tests. In contrast, the stress-induced opioid mediated responses were modified in CB1 mutants. Indeed, these mutants did not exhibit antinociception following a forced swim in water at 34 degrees C and presented a decrease in the immobility induced by the previous exposure to electric footshock. However, the antinociception induced by a forced swim in water at 10 degrees C was preserved in CB1 mutants. These results indicate that CB1 receptors are not involved in the antinociceptive responses to exogenous opioids, but that a physiological interaction between the opioid and cannabinoid systems is necessary to allow the development of opioid-mediated responses to stress.     

不同频率电针对下肢胫后神经体感诱发电位痛成分P_(250)—N_(350)的影响

目的 :观察不同频率电针穴位的镇痛作用规律。方法 :采用电刺激正常人下肢胫后神经获得痛相关成分P2 50 —N350 复合波作为反映疼痛的客观指标 ,观察不同频率电针穴位对痛相关成分P2 50 —N350 波幅、潜伏期变化的影响。结果 :2Hz组针中 1 0、2 0minP2 50 —N350 波幅明显降低 ,差异显著 ,分别为P <0 0 1、P <0 0 0 1 ;40Hz组针中 2 0minP2 50 —N350 波幅明显降低 ,差异显著 ,P <0 0 0 1 ;2Hz、40Hz组针后波幅仍维持较低水平 ,差异显著 ,分别为P <0 0 0 1、P <0 0 1。结论 :2Hz、40Hz电针对SEPS 皮层痛成分有明显的抑制效应 ;针后具有强而持久的后效应     

温经化瘀合剂药效学研究

目的：观察温经化瘀合剂(当归、川芎、香附、益母草等)治疗痛经、月经不调等作用。方法：对小鼠子宫、卵巢进行重量测定，二甲苯致小鼠耳肿胀法，缩宫素诱发大鼠痛经模型和前列腺素E1诱发小鼠痛经模型法，对大鼠离体子宫收缩活动的影响。结果：温经化瘀合剂能明显增加小鼠子宫重量，减轻二甲苯引起的小鼠耳肿胀度，减少缩宫素所致大鼠扭体反应次数和前列腺素E1所致小鼠扭体反应次数，既能使正常大鼠离体子宫收缩，又能对抗缩宫素对大鼠离体子宫的收缩作用。结论：温经化瘀合剂具有镇痛、抗炎作用，对子宫有双向调节作用。     

胃癌术后镇痛对肠功能恢复的观察与护理

目的　探讨胃癌手术后硬膜外持续镇痛对患者肠功能的影响。方法　对 6 0例胃癌术后病人进行随机分组 ,PCEA(pa tientcontrolledEpiduralanalgesia)组 :采用硬膜外持续镇痛 (30例 ) ;对照组 :采用间断注射镇痛剂 (30例 ) ,观察肠蠕动、肛门排气时间及不良反应。结果　肠蠕动恢复时间PCEA组 (5 2 1± 4 3)h ,对照组 (5 1 5± 4 4 )h。肛门排气时间PCEA组 (6 5 4±7 5 )h ,对照组 (5 6 1± 9 3)h。PCEA组不良反应明显少于对照组。结论　术后镇痛不影响胃癌术后肠蠕动恢复 ,但应加强术后早期活动的指导     

左旋精氨酸及左旋精氨酸脱羧酶抗血清对吗啡镇痛及耐受的影响

目的:分析左旋精氨酸及左旋精氨酸脱羧酶(L-ADC)对吗啡镇痛及其所致耐受的影响。方法:用家兔制备L-ADC多克隆抗体;以小鼠热辐射甩尾法和小鼠55℃热板测痛模型分析此抗体及左旋精氨酸对吗啡镇痛和耐受的影响。结果:在热辐射甩尾和热板测痛模型中,0.5-50mg·kg~(-1)的左旋精氨酸(sc)不影响吗啡镇痛和耐受(P>0.05)。L-ADC抗血清(脑室注射,1:1000-1:10稀释)能对抗吗啡镇痛作用,在热辐射甩尾和热板测痛模型中,它能使吗啡可能最大镇痛百分率分别从94.3％和80.6％下降到57.7％和42.9％(P<0.01)。吗啡连续处理小鼠3d后形成耐受:在热辐射甩尾和热板测痛模型中,吗啡的可能最大镇痛百分率分别从90.3％和80.3％下降到47.2％和40.5％;L-ADC抗血清能进一步加重吗啡所致耐受,其可能最大镇痛百分率进一步下降至19.8％和27.7％(P<0.01)。结论:L-ADC可能参与调节了吗啡镇痛及耐受形成过程;而左旋精氨酸不影响吗啡镇痛和耐受。     

腰硬联合麻醉用于分娩镇痛的临床研究

目的：探讨腰硬联合麻醉(CSEA)减轻或消除产痛以及对产程、胎儿、分娩方式的影响。方法：选择305例无产科及麻醉禁忌症的初产妇，在产程进入活跃早期宫口开大3—4cm时，给予腰硬联合麻醉(观察组)，并与同期条件相似、未给予任何镇痛方法的305例初产妇进行对比(对照组)。比较两组产妇产痛程度、产程进展速度、分娩方式及对胎儿的影响。结果：观察组镇痛有效率较对照组明显升高(P＜0．01)，又活跃期较对照组明显缩短，宫颈口扩张速度加快，经阴道分娩助产率增高(P＜0．05)。胎儿窘迫及新生儿窒息、产后出血发生率两组则无显的统计学意义(P＞0．05)。结论：CSEA可有效用于分娩镇痛、加速产程，且对胎儿及产妇无不良影响，值得推广应用。     

利鲁唑对吗啡镇痛、耐受和依赖作用的影响(英文)

目的　研究利鲁唑对阿片镇痛、耐受及躯体功能的调节。方法　采用冰醋酸扭体 ,5 5℃热板法和热辐射甩尾法观察利鲁唑对小鼠痛阈及吗啡镇痛效应的影响 ;采用小鼠急性和慢性吗啡耐受模型及小鼠吗啡依赖模型 ,观察利鲁唑对吗啡耐受和依赖的作用。结果　单独皮下注射利鲁唑 2 .5～ 10mg·kg- 1在以上 3种模型无镇痛作用 ,然而能剂量依赖性地增强吗啡镇痛效应。利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地对抗吗啡引起的急性和慢性耐受。在小鼠吗啡依赖模型中 ,利鲁唑 2 .5～ 10mg·kg- 1剂量依赖性地抑制吗啡戒断症状的产生。结论　利鲁唑自身无镇痛作用 ,但能显著增强吗啡镇痛效应 ,并能预防吗啡所引起的耐受和依赖     

右旋酮洛芬的解热镇痛作用

目的 研究右旋酮洛芬(Dexketoprofen, D-KP)的解热镇痛作用.方法 采用小鼠热板法和热辐射甩尾法两种镇痛实验模型;角叉菜胶诱导的大鼠和伤寒疫苗诱导的兔体温升高两种实验模型.结果 D-KP(5、10、20 mg.kg-1)能明显延长小鼠热板和热辐射甩尾的痛阈时间;D-KP(2.5、5、10 mg.kg-1)对角叉菜胶诱发大鼠的体温升高、D-KP(1.25、2.5、5 mg.kg-1)对伤寒疫苗诱发兔的体温升高均有明显的降温作用.结论 D-KP具有良好的解热镇痛作用.     

术前口服依他昔布对妇科手术后病人自控镇痛的影响

目的:观察妇科开腹手术患者术前给予依他昔布120mg对术后自控镇痛(PCA)吗啡用量的影响及其副作用。方法:随机选取全麻下接受妇科开腹全子宫(双附件)切除患者40例,术前分别给予安慰剂或依他昔布120mg口服。在手术后观察24h患者PCA吗啡用量,同时记录患者的疼痛评分和满意度评分,并观察不良反应。结果:术后PCA吗啡24h消耗量在依他昔布组为9.4±7.6mg,显著低于安慰剂组15.7±8.9mg。两组患者24h内对PCA的按压次数依他昔布组也低于安慰剂组(P<0.05)。其中术后3、6、8和12hPCA吗啡消耗量在两组间无显著差异。两组患者术后24h疼痛评分和对镇痛治疗的满意度也无差异。两组患者不良反应的发生率亦无差别。结论:在妇科开腹手术患者术前应用依他昔布120mg可使患者术后PCA吗啡消耗量降低,且在术后12h后下降明显。未发现与依他昔布应用相关的副作用。