Time course and effective sites for inhibition from midbrain periaqueductal gray of spinal dorsal horn neuronal responses to cutaneous stimuli in the cat

Summary Inhibition of spinal dorsal horn neuronal responses to noxious (50 °C) skin heating by stimulation of the midbrain periaqueductal gray (PAG) was quantitatively investigated in cats anesthetized with sodium pentobarbital and nitrous oxide. Systematic variation of the interval between onset of PAG stimulation (PAGS) and onset of noxious skin heating revealed that a marked reduction of spinal unit heat-evoked discharges occured immediately upon onset of PAGS, and ceased immediately at offset of PAGS with a post-stimulation excitatory rebound. Stimulation at sites in both ventral and dorsal PAG produced inhibition, the strength of which increased sometimes in a linear manner with increasing strength of PAGS. Thresholds for the generation of descending inhibition were higher in dorsal than ventral PAG. PAGS also inhibited spinal unit responses to non-noxious skin stimulation (brushing of hairs). Descending inhibition from PAG is considered as a possible mechanism for analgesia produced by stimulation of PAG and other brainstem structures.The work was supported by a grant from the Deutsche Forschungsgemeinschaft (Zi 110)     

Report of the symposium

Summary The past decades have seen considerable shifts of emphasis in surgical care. The recognition that pus was not laudable, was followed by a realisation that not all complications were inevitable and that prophylaxis could effectively reduce the incidence of most common problems in the post-operative period. As anaesthesia has become safer, it has been possible to embark on more intricate and prolonged procedures and for sufficient time to be available to ensure adequate intraoperative care.These two phenomena have firstly increased the complexity of management in the post-operative period, and have brought this aspect of surgical care more obviously to the limelight. However, many separate disciplines are involved in the care of the patient post-operatively, and the Symposium was organised¹ to bring the different groups together to identify the areas of recent development in the different specialities and to integrate the overall care of the individual patient.Abbreviations ARDS adult respiratory distress syndrome - DIC disseminated intravascular clotting     

Intra-articular morphine versus bupivacaine for postoperative analgesia following knee arthroscopy

In a prospective, double blind, randomized study, 30 ASA I patients were allocated to three groups depending on the drug injected intra-articularly, in an attempt to establish the best postoperative analgesic protocol following knee arthroscopy. Group 1 received 3 mg of preservative-free morphine in 25 ml saline; group 2, 5 mg of preservative-free morphine in 25 ml saline; and group 3, 25 ml 0.25% bupivacaine. The degree of postoperative pain was evaluated by visual analogue scale and the need for additional analgesics at 1, 2, 3, 8 and 24 h. We conclude that bupivacaine 0.25% provides analgesia of early onset and of short duration. While 3 mg-preservative free morphine provides moderate postoperative analgesia with peak effect during the eighth postoperative hour, 5 mg preservative-free morphine provides effective and long lasting (more than 24 h) pain relief. No side effects were noted.     

Agonistic behaviour in rats: evidence for non-involvement of opioid mechanisms

It has recently been proposed that a stress-activated, endogenous analgesia mechanism would be adaptive in situations in which pain perception might otherwise disrupt effective behavioural performance. In a semi-natural test situation, the current study examined two predictions arising from this hypothesis: (1) in a manner analogous to other stressors, agonistic experience should produce analgesia and, if naloxone-sensitive opioid mechanisms are implicated, then (2) pretreatment with naloxone should block the development of this response and alter the displayed behaviour patterns. Neither prediction was substantiated by the data. Experience of an agonistic encounter failed to produce analgesia in either resident or intruder animals. Furthermore, naloxone hydrochloride (1-25 mg/kg) was also without effect on patterns of offense or defense. Data are discussed in relation to the critical nature of the stimulus factors involved in the activation of endogenous analgesic mechanisms and the postulated involvement of such mechanisms in biologically-adaptive behaviours.     

Naloxone injections into the periaqueductal grey area and arcuate nucleus block analgesia in defeated mice

In a situation of social conflict, mice that are defeated by an opponent exhibit a marked analgesia. Microinjections of naloxone (1 or 10 g) into the periaqueductal grey area (PAG) or into the region of the arcuate nucleus prior to the defeat prevented the emergence of analgesia. Microinjections of morphine (5 g) into these sites had previously been shown to produce profound analgesia. Mice whose adrenals were removed rapidly developed analgesia when attacked by a stimulus animal. Injection of naloxone into PAG also antagonized defeat-induced analgesia in adrenalectomized mice. These observations indicate that sites and processes in the brain rather than in the periphery are responsible for the development of analgesia in mice that are subjected to social defeat.     

Pharmacology of spinal adrenergic systems which modulate spinal nociceptive processing

Spinopetal pathways may be activated by a variety of brainstem manipulations including microinjections of morphine which are known to modulate spinal nociceptive processing. Based on the ability of these manipulations to release spinal noradrenalin; the ability to reverse the antinociceptive effects by intrathecal adrenergic antagonists and the fact that intrathecal injections of noradrenalin mimic the antinociceptive effect, it appears that the descending modulation may be mediated by descending noradrenergic systems. Examination of the spinal receptor systems with intrathecally administered agents indicates that spinal alpha, but not beta adrenergic receptor agonists produce a powerful analgesia as measured on a variety of reflex and operant measures in mouse, rat, cat, primate and man. On the basis of agonist and antagonist structure-activity relationships it appears that a significant effect can be produced in the absence of any detectable effect on motor function by the occupation of spinal alpha 2 receptors. Distinguishable alpha 1 receptors also appear "analgetically-coupled," but their effects are uniformly contaminated by signs of cutaneous hyperreflexia at doses required to produce analgesia. The ordering of potency with which intrathecal adrenergic antagonists reverse the effects of intrathecal noradrenalin is indistinguishable from that of the reversal by these intrathecal agents of the antinociceptive effects evoked by brainstem morphine. This suggests that the population of spinal receptors acted upon by exogenously administered adrenergic agonists and endogenously released noradrenaline have indistinguishable characteristics.     

Species differences in the relative analgesic potencies of some classical opiates and opioid peptides

The analgesic ED₅₀ values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain d-amino acid in position 2 and d- or l-sulfonic (or phosphonic) acid residue in position 5). -Endorpin, d-Met², Pro⁵-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of - and -receptors in mediation of the analgesic effect induced by different types of opioids.     

2021年ACOG关于产后阶梯式多模式药物镇痛的建议及要点解读

产后疼痛是困扰产妇的常见问题,如治疗不当可能会导致阿片类药物滥用、产后抑郁和疼痛长期存在等不良后果。因此,美国妇产科医师学会（American College of Obstetricians and Gynecologists,ACOG）于2021年9月提出了针对产后疼痛的临床共识,专门对产后疼痛的一般管理、阴道分娩、剖宫产术后、母乳喂养时及出院后疼痛的处置给出了治疗建议与指导,强调了阶梯式多模式药物镇痛方法与个体化用药原则。推荐临床用药可遵循“非阿片类镇痛药（如对乙酰氨基酚和非甾体抗炎药）—弱阿片类药物—强阿片类药物（必要时）”阶梯式给药原则,并可合理联合用药。对此进行简要介绍与要点解读。     

罗哌卡因用于下腹部手术后硬膜外自控镇痛的评价

目的　评价罗哌卡因用于下腹部手术后镇痛的有效性和不良反应。方法　 6 0例择期下腹部手术患者 ,随机分为两组 ,第Ⅰ组为罗哌卡因复合PCA吗啡治疗组 ,第Ⅱ组为安慰剂复合PCA吗啡组。观察罗哌卡因镇痛效果及对运动神经阻滞的影响 ,对比两组的血液动力学变化、吗啡用量和不良反应。结果　罗哌卡因复合PCA吗啡治疗组的术后疼痛评分及不良反应明显低于安慰剂复合PCA吗啡组 ,且第Ⅰ组的吗啡用量明显低于安慰剂组。结论　 0 2 %罗哌卡因复合PCA吗啡可安全有效地应用于下腹部术后的镇痛。     

人工流产术前宫颈及子宫内膜麻醉的镇痛效果探讨

目的　探讨宫颈与子宫内膜两部位联合麻醉、普鲁卡因与利多卡因两药物配合应用在人工流产术中的镇痛效果。方法　人工流产术前对麻醉组 10 6例行普鲁卡因宫颈浸润麻醉和利多卡因子宫内膜表面麻醉。术中记录受术者腹痛程度、无阻力插入宫颈内口的扩张器号、出血量、人流综合征例数等指标。按照世界卫生组织规定疼痛标准及人工流产综合征反应进行评价 ,同期选择按传统机械扩宫法 10 4例做对照。结果　麻醉组镇痛有效率95 3% ,宫口松驰有效率 95 3% ,人流综合征无 1例发生。两组比较P均 <0 0 0 1。两组出血量比较无差异 ,无利多卡因毒性反应发生。结论　人工流产术前普鲁卡因宫颈浸润麻醉和利多卡因子宫内膜表面麻醉镇痛效果显著 ,可大大降低人流综合征的发生 ,避免利多卡因的毒性反应