Spinal NTS1 receptors regulate nociceptive signaling in a rat formalin tonic pain model

Central administration of the neuropeptide neurotensin (NT) was shown to induce antinociceptive responses both spinally and supraspinally. Although NTS2 receptors play an important role in modulating the activity of spinal neurons, we have recently implicated NTS1 receptors in NT's analgesic effects in acute spinal pain paradigms. The current experiments were thus designed to examine the antinociceptive effects of intrathecal administration of NTS1 agonists in formalin-induced tonic pain in rats. We first established, using immunoblotting and immunohistochemical approaches, that NTS1 receptors were present in small- and medium-sized dorsal root ganglion cells and localized in the superficial layers of the dorsal horn of the spinal cord. We then examined the effects of intrathecal injection of NT (1–15 μg/kg) or NTS1 preferring agonists on the nocifensive response to intraplantar formalin. Both NTS1-agonists, PD149163 (10–120 μg/kg) and NT69L (1–100 μg/kg), dose-dependently attenuated the formalin-induced behaviors. Accordingly, NTS1 agonists markedly suppressed pain-evoked c- fos expression in the superficial, nucleus proprius and neck regions of the spinal dorsal horn. The concomitant administration of PD149163 with the NTS1 antagonist SR48692 (3 μg/kg) significantly reversed PD149163-induced antinociception, confirming the implication of NTS1 in tonic pain. In contrast, NT69L's analgesic effects were partly abolished by co-administration of SR48692, indicating that NT69L-induced effects may also be exerted through interaction with NTS2. These results demonstrate that NTS1 receptors play a key role in the mediation of the analgesic effects of NT in persistent pain and suggest that NTS1-selective agonists may represent a new line of analgesic compounds.     

两面针提取物(S-O)对小鼠镇痛、抗炎和止血作用的研究

本研究对两面针根的提取物S-O进行了镇痛、止血和抗炎药理实验,每种作用选用两种实验方法来评价。镇痛作用采用热板法和扭体法。热板法实验显示,S-O在150mg/kg剂量时,小鼠痛阈值明显提高（P〈0．01）;扭体法实验显示,S-O在150mg/kg剂量为时,对冰醋酸致痛的小鼠扭体反应次数减少了70．96％（P〈0．01）。抗炎实验采用二甲苯致小鼠耳廓肿胀法及腹腔染料渗出法。二甲苯致炎剂实验表明,S-O在150mg/kg剂量时,对二甲苯所致小鼠耳廓肿胀有明显抑制作用,抑制率为63．45％（P〈0．01）;冰醋酸所致的腹腔毛细血管通透性实验中,S-O在150mg/kg和75mg/kg两个剂量组时,对小鼠的抗炎效果分别为52．94％（P〈0．01）和52．00％（P〈0．01）。止血实验采用毛细玻璃管法和载玻片法。毛细玻璃管实验表明S-O在150mg/kg和75mg/kg两个剂量时,凝血时间明显缩短（P〈0．01）;载玻片实验表明S-O在150mg/kg剂量时,凝血时间明显缩短（P〈0．01）。总之,两面针中提取物S-O对小鼠具有显著的镇痛、止血和抗炎作用。     

前列腺Ⅰ号抗炎镇痛作用以及抗前列腺炎的实验研究

采用热板法和扭体法观察前列腺Ⅰ号抗炎、镇痛以及抗大鼠实验性前列腺炎的作用。采用小鼠耳廓二甲苯制炎法观察抗炎作用,前列腺炎模型采用向大鼠前列腺组织内注入角叉菜胶的方法。结果显示前列腺Ⅰ号能减少小鼠扭体反应数,延长小鼠热板法引起的痛反应潜伏期,对小鼠耳廓肿胀有明显的抑制作用,前列腺炎模型试验中,前列腺液检查卵磷脂小体明显增加,白细胞数降低。因此前列腺Ⅰ号具有明显的抗炎、镇痛以及抗前列腺炎的作用。     

Putative Nociceptive Modulatory Neurons in the Rostral Ventromedial Medulla of the Rat Display Highly Correlated Firing Patterns

Recent work in this laboratory has identified two classes of putative nociceptive modulating neurons in the rostral ventromedial medulla (RVM) of the rat: “off-cells,” which pause beginning just prior to the tail flick response (TF) evoked by noxious heat, and “on-cells,” which accelerate shortly before the occurrence of the TF. In the unstimulated, lightly anesthetized rat, the spontaneous firing pattern of individual on- and off-cells consists of alternating periods of silence and activity lasting from several seconds to a few minutes.

In the present study, simultaneous recordings were made from pairs of TF-related neurons, and the relationships among the firing patterns of cells within a class and between cells of different classes were determined. All cells of a given class showed fluctuations in spontaneous discharge that were in phase. On the other hand, there was a striking reciprocity of firing between the two cell classes, such that a decrease in activity of cells of one class was accompanied by an increase in activity of cells of the other class.

These observations point to the existence of integrating mechanisms that coordinate the activity of all members of each class of TF-related neurons. Thus, the pattern of activity of any single on- or off-cell provides a useful index of the excitability of all cells of that class. Moreover, because of the highly reciprocal nature of the firing of the two classes, it is possible to infer the current state of both cell populations from the pattern of activity of any single TF-related neuron.     

Renal impairment and analgesia: From effectiveness to adverse effects

Kidney pain is one of the clinically significant features of renal dysfunction. Mild to severe pain is seen in the lower back area. Painkillers are mostly recommended in these cases to relieve the symptom. Yet, several analgesics are associated with side effects that can worsen the state of the disease. This review is based on the studies conducted in these aspects analgesics used to treat kidney pain and their effectiveness, renal consequences of postoperative analgesia, and pharmacogenetics of these palliatives are briefly summarized in this paper.     

Effects of topical anaesthetic and buccal meloxicam on average daily gain,behaviour and inflammation of unweaned beef calves following surgical castration

Although the pain caused by castration of calves is a significant animal welfare issue for the beef industry, analgesia is not always used for this procedure, largely because of practical limitations associated with injectable forms of pain relief. Novel analgesic formulations have now been developed for livestock to allow topical and buccal administration, offering practical options to improve cattle welfare if shown to be effective. To assess the effects of topical anaesthetic (TA) and buccal meloxicam (BM) on average daily gain (ADG), behaviour and inflammation following surgical castration of beef calves, a total of 50 unweaned bull calves were randomly allocated to: (1) sham castration (SHAM, n=10); (2) surgical castration (C, n=10); (3) surgical castration with pre-operative buccal meloxicam (CBM, n=10); (4) surgical castration with post-operative topical anaesthetic (CTA, n=10); and (5) surgical castration with pre-operative buccal meloxicam and post-operative topical anaesthetic (CBMTA, n=10). Calves were recorded on video for 5 h following treatment and the frequency and duration of specific behaviours displayed by each animal was later observed for 5 min every hour (total of 25 min). Average daily gain was calculated 1, 2 and 6 days following treatment. Scrotal diameter measurements and photographs of wounds were collected from all castrated calves 1, 2 and 6 days following treatment to evaluate inflammation and wound healing. Infrared photographs were used to identify maximum scrotal temperature. Digital photographs were used to visually score wounds on a numerical rating scale of 1 to 5, with signs of inflammation increasing and signs of healing decreasing with progressive scores. Sham castration calves displayed significantly less, and C calves displayed significantly more foot stamps than all other calves (P=0.005). Observations on the duration of time that calves displayed a hypometric ‘stiff gait’ locomotion, indicated that SHAM calves tended to spend no time, C calves tended to spend the greatest time and all other calves tended to spend an intermediate time displaying this behaviour (P=0.06). Maximum scrotal temperatures were lower in CBM and CBMTA calves than C and CTA calves 2 days following treatment (P=0.004). There was no significant effect of treatment on ADG (P=0.7), scrotal diameter (P=0.09) or wound morphology score (P=0.5). These results suggest that TA and BM, alone or in combination, reduced pain and BM reduced inflammation following surgical castration of calves.     

帕瑞昔布联合股神经阻滞用于膝关节置换术后镇痛的效果评价及其对患者免疫功能的影响

目的:探讨帕瑞昔布联合股神经阻滞用于膝关节置换术后镇痛的效果及对患者免疫功能的影响。方法:选择2016年10月-2017年10月我院骨科住院部收治并行单侧膝关节置换的患者108例,按镇痛方式分为对照组和观察组各54例。对照组患者采用单纯股神经阻滞,观察组采用股神经阻滞联合帕瑞昔布。比较两组静息及活动状态下术后VAS评分、术后膝关节HSS评分、不良反应的发生情况及免疫指标的变化情况。结果:静息及活动状态下,观察组术后VAS评分均明显低于对照组(P均0.05),膝关节HSS评分显著高于对照组(P0.05)。两组术后不良反应的发生情况比较差异无统计学意义(P0.05)。手术结束时,两组CD4~+较麻醉前均显著下降(P均0.05);术后72 h,两组CD4~+、CD8~+及CD4~+/CD8~+较麻醉前均无显著差异(P均0.05)。观察组术后72 h CD4~+比对照组高(P0.05),而CD4~+/CD8~+显著低于对照组(P0.05)。结论:帕瑞昔布联合股神经阻滞对膝关节置换术后镇痛临床效果好,利于保护和改善患者免疫功能,促进膝关节功能的康复。     

氟哌利多增强电针镇痛时大鼠脑内微透析液中单胺类递质的变化

本文采用大鼠脑内微透析及高效液相色谱电化学联检技术,观察多巴胺受体拮抗剂氟哌利多加强电针镇痛时大鼠脑人微透析液中单胺类递质的变化,从而探讨药物加强针刺镇痛的机制。结果显示,ＥＡ与ＤＡ及其代谢产物高香草酸在透析液中含量增加,ＤＲＯ与ＥＡ合用后,两者的含量较单用ＥＡ又有明显增加。     

100Hz电针刺受时大鼠脑和脊髓k受体结构特性的改变

西方采用放射配体结合实验研究了１００ＨＺ电针耐受发生发展过程中大鼠脑和脊髓Ｋ受体结构特性的变化。大鼠每天给予１００ＨＺ电针１次,连续７ｄ。分别在电针的第１、３、５、７天取不同脑区进行观察。     

Evaluation of tissue changes following intramuscular infiltration of lidocaine in rainbow trout Oncorhynchus mykiss

Rainbow trout Oncorhynchus mykiss were infiltrated with either saline or lidocaine adjacent to the dorsal fin to assess histopathological changes. Infiltration was done as if it were being used as a local anaesthetic. Tissue lesions and associated tissue healing were examined over a period of 30 days. Most changes occurred at the cranial site of where the solution was first infiltrated. The infiltration of a dose of 10 mg kg^?1 of lidocaine appears to have damaged the skeletal muscle and connective tissues more than a similar volume of saline, especially during the first 15 days. The primary changes included haemorrhage, inflammation and muscle degeneration and necrosis. By day 30 post‐infiltration inflammatory lesions were either nearly or completely absent, signs of myofibre regeneration were noted in only one fish. This experiment shows local anaesthetics and saline can produce localized tissue damage, especially during the first 2 weeks post infiltration. Care should be taken to allow the fish to heal for at least 30 days and probably more, no matter the solution administered, especially if giving repeated injections or infiltrations at the same site.