Nociceptive and edematogenic responses elicited by a crude bristle extract of Lonomia obliqua caterpillars.

Lyophilized Lonomia obliqua crude bristle extract (LOCBE) diluted in physiological saline (15, 35 and 50 microg of protein/paw) was injected in the plantar surface of the hind paw of the rat, causing a nociceptive response which lasted from 30 to a maximum of 50 min, peaking in the first 5 min. The animals also presented hematuria and nasal bleeding. Nociception was inhibited by indomethacin pretreatment (2.5 mg/kg, i.p., 60 min before), but not by guanethidine (30 mg/kg/day, s.c., for 3 days) or loratadine (5 mg/kg, p.o., 60 min before). LOCBE injection also produced paw edema peaking 1 h after injection and lasting for 6 h. Loratadine pretreatment, but neither guanethidine nor indomethacin, reduced edema. After the period of overt nociception, a nociceptive aftersensation response could be evoked up to 6 h after by immersing the paw into cold water (15 degrees C) for 10 s. Capsaicin (1.6 microg), formalin (0.5%) or prostaglandin E(2) (500 ng) did not produce the same aftersensation phenomenon. These results suggest that LOCBE-induced nociception is largely facilitated by prostaglandin production, and edematogenic response seems to be facilitated by prostanoids and histamine. Finally, LOCBE induced a state of sensitization to cold, which seemed to be specific as it was not caused by other noxious chemicals.     

多塞平对骨癌疼痛模型大鼠的镇痛作用研究

目的:研究多塞平对骨癌疼痛模型大鼠的镇痛作用。方法:取大鼠90只,其中10只为正常组,另80只胫骨注射含人乳腺癌Walker256细胞株的大鼠细胞液建立骨癌疼痛模型,待模型成功稳定后分为模型组、吗啡组(1000μg·kg-1)、多塞平(3、10、30、100、300、1000μg·kg-1)组,鞘内给予相应药物,考察给药后0.5、1、2、4h时各组大鼠的双侧脚痛阈值,并计算多塞平的最大镇痛效应。结果:多塞平与吗啡在给药后0.5h即产生镇痛作用,给药后1h镇痛作用达到高峰;多塞平各剂量组大鼠造模对侧脚痛阈值无明显变化,造模同侧脚痛阈值升高与剂量呈正相关;多塞平1000μg·kg-1的最大镇痛效应为67.7%,半数有效量为46.6μg·kg-1,与吗啡1000μg·kg-1的镇痛效应比较无明显差异。结论:多塞平对骨癌疼痛模型大鼠具有镇痛作用。     

Analgesic effects of morphine and loperamide in the rat formalin test: interactions with NMDA receptor antagonists

To reveal peripheral components of opiate analgesia, effects of loperamide, opioid agonist which does not penetrate the blood-brain barrier, were examined in formalin and acute thermal pain tests in comparison with morphine. Formalin administration induces pain behaviour such licking/biting of injected paw expressed as two phases. The first phase is caused by C-fibre activation due to peripheral stimulation, the second phase attributed to ongoing input from peripheral site, leading to spinal hyperexcitability, which is dependent on N-methyl-D-aspartate (NMDA) receptor activation. Loperamide (3-10 mg/kg) and morphine (6 mg/kg) reduced formalin-induced nociceptive behaviours and these effects were reversed by naloxone methiodide (0.03-10 mg/kg), opioid receptor antagonist which poorly penetrates the blood-brain barrier. Loperamide action was enhanced only by centrally active NMDA receptor antagonists memantine (3 mg/kg) and CGP 37849 (3 mg/kg), but not by NMDA/glycineB receptor antagonists showing weak or no central nervous system (CNS) activity. Present results suggest that central NMDA receptor blockade may be necessary to enhance analgesia induced through peripheral opioid mechanisms in formalin-evoked nociception.     

Antinociceptive effects of ceftriaxone in formalin-induced nociception

Ceftriaxone (CFX) is a β-lactam antibiotic with analgesic properties. However, its role in the formalin-induced nociception remains unknown. The purpose of this study was to investigate the antinociceptive effect of CFX in the 1% formalin test in rats. Formalin induced a typical nociceptive response (flinching behavior) of two phases. Local peripheral pretreatment (20 min) with CFX (400–800 μg/paw) slightly attenuated the flinching behavior in phase 2, but not phase 1. Acute intraperitoneal pretreatment (20 min) also reduced phase 2 of the formalin test. In both cases, CFX induced a dose-dependent antinociception. We also tested the effect of CFX 1 day after its administration and in two schedules of repeated administration. One-day pretreatment with CFX (50–400 mg/kg, ip) induced a dose-dependent antinociceptive effect in formalin-treated rats. Repeated administration (daily during 3 or 7 days) with CFX (50–400 mg/kg, ip) diminished formalin-induced nociception. Results suggest that local or systemic as well as single or repeated administration of CFX reduces formalin-induced nociception.     

Chronic administration of desipramine and zimelidine changes the behavioural response in the formalin test in rats.

In studies of the effect on nociception of chronic administration of antidepressants, the stress of the injections may influence the results. In this experiment, desipramine or zimelidine were administered in the drinking water of rats, in a concentration yielding a dose of approximately 8 mg/kg/24 hr. Desipramine, given both for a short time (24 hr) and chronically (14 days), induced antinociception in the increasing temperature hot-plate test; zimelidine did not significantly influence the results of this test. In the tail-flick test, neither short-term nor chronic administration of these antidepressants had any effect on nociception, when correction was made for the changes in the temperature of the tail skin. In the formalin test, nine behavioural categories were scored for 1 hr and the data were treated statistically, using a multivariate analysis. Chronic administration of desipramine increased nociceptive behaviour during the first 10 min of the test. Desipramine and, to a lesser extent, zimelidine, changed the response in the late phase (10-60 min), showing less focussed pain-related behaviour (jerks and shaking, licking and biting of the injected paw) and more non-focussed pain-related behaviour (activity states with elevation or protection of the injected paw). It was concluded that desipramine is antinociceptive in the increasing temperature hot-plate test. Desipramine and zimelidine, administered chronically, modify the late phase of the formalin test towards less focussed pain-related behaviour, suggesting an antinociceptive effect. Multivariate analysis of the data of the formalin test seemed to be of value for the interpretation of the data.     

Influence of pre-operative ketoprofen administration (preemptive analgesia) on analgesic requirement and the level of prostaglandins in the early postoperative period

The aim of this study was to examine the effect of ketoprofen used in preemptive analgesia on the intensity of pain and requirement for analgesics in the perioperative period. Sixty patients scheduled for elective lumbar disc prolapse surgery were randomly divided into two groups. In the PRE group (n = 30) ketoprofen was administered one hour before incision. In the POST group ( n = 30) ketoprofen was used immediately after the surgery. The operation was performed under general anesthesia. Postoperative analgesia was realized by NCA (Nurse Controlled Analgesia) and the "required" dose of ketoprofen was 100 mg. After the operation, pain intensity was measured using visual-analog scale (VAS), ketoprofen requirements, the time to the first dose of ketoprofen, and levels of prostaglandin E(2) (PEG(2)) in blood serum were compared. There were no differences between the groups in the VAS pain scores, and levels of PGE(2) in blood serum. However, in patients of PRE group who had received preemptive analgesia, a significantly lower total consumption of ketoprofen, as compared with POST group, was observed between 12th and 36th postoperative hours. It was also found that the time which elapsed between the end of the operation and the first NCA activation was significantly shorter in the PRE group, as compared with the POST group. The results of our study confirm the possibility of modifying the nociception process in the perioperative period through preemptive analgesia by ketoprofen.     

Evaluation of the anti-inflammatory, anti-nociceptive and gastric effects of Ginkgo biloba in the rat.

Ginkgo biloba extract (GbE) was assessed in models of acute inflammation induced by carrageenan, formalin or capsaicin in the rat, in models of nociceptive pain, such as hot-plate (55 degrees C) latency, tail-electric stimulation assay and capsaicin-induced paw licking and in the model of acute gastric damage induced by indomethacin. The agent showed marked anti-inflammatory activity in the carrageenan model of paw oedema. When given subcutaneously (s.c.) (25 and 50 mg kg(-1)) 30 min before challenge, GbE inhibited paw oedema with a maximal effect of 43.7 and 56.9%, respectively, at 2h post-carrageenan. Significant inhibition of oedema was also observed when GbE (50 mg kg(-1), s.c.) was given 30 min after carrageenan challenge. The agent was also active p.o. in acute inflammation caused by carrageenan. The administration of GbE with indomethacin, rofecoxib, celecoxib, dexamethasone or melatonin resulted in an additive effect. GbE (50 mg kg(-1), s.c.) caused significant inhibition of formalin-induced paw oedema, but did not reduce the capsaicin-induced paw oedema. In tests of nociception, GbE (25, 50 or 100 mg kg(-1)) decreased in dose-dependent manner the capsaicin-induced hind paw licking time and was similarly effective in the hot-plate assay of nociception. In contrast, when assessed in the tail-electric stimulation test, GbE was only effective in the highest dose (100 mg kg(-1)). In pylorus-ligated rats, GbE (25 or 50 mg kg(-1)) increased gastric acid secretion, but reduced gastric mucosal damage caused by IND. Results suggest that GbE may be of clinical value as an anti-inflammatory and analgesic drug alone or in conjunction with NSAIDs.     

Large-amplitude 5-HT1A receptor activation: a new mechanism of profound,central analgesia

We report the discovery of F 13640 and evidence suggesting this agent to produce powerful, broad-spectrum analgesia by novel molecular and neuroadaptative mechanisms. F 13640 stimulates G(alphaomicron) protein coupling to 5-HT(1A) receptors to an extent unprecedented by selective, non-native 5-HT(1A) ligands. Fifteen minutes after its injection in normal rats, F 13640 (0.01-2.5 mg/kg) decreases the vocalization threshold to paw pressure; 15 min upon injection in rats that are exposed to formalin-induced tonic nociception, F 13640 inhibits pain behavior. The initial hyperalgesia induced by 0.63 mg/kg F 13640 was followed, 8 hrs later, by paradoxical hypo-algesia; 5 mg/kg of morphine produces the opposite effects (i.e., hypo-algesia followed by hyper-algesia). Repeated F 13640 injections cause an increase in the basal vocalization threshold and a reduction of F 13640-produced hyperalgesia; in these conditions, morphine causes basal hyperalgesia and antinociceptive tolerance. Continuous two-week infusion of F 13640 (0.63 mg/day) exerts little effect on the threshold in normal rats, but markedly reduces analgesic self-administration in arthritic rats. F 13640 infusion also decreases allodynic responses to tactile and thermal stimulations in rats sustaining spinal cord or sciatic nerve injury. In these models of chronic nociceptive and neuropathic pain, the analgesia afforded by F 13640 consistently surpasses that of morphine (5 mg/day), imipramine (2.5 mg/day), ketamine (20 mg/day) and gabapentin (10 mg/day). Very-high-efficacy 5-HT(1A) receptor activation constitutes a novel mechanism of central analgesia that grows rather than decays with chronicity, that is amplified by nociceptive stimulation, and that may uniquely relieve persistent nociceptive and neuropathic pains.     

Differential effects of phenylbutazone and local anesthetics on nociception in the equine

The effects of procaine, mepivacaine and phenylbutazone on pain perception in the equine were studied using two behavioral assays of nociception; the thermal evoked hoof withdrawal reflex and skin twitch reflex. Pain perception threshold was measured as the latency from onset of thermal stimuli to reflex withdrawal of the forelimb or contraction of the cutaneous musculature. Procaine 2% and mepivacaine 2% prolonged the hoof withdrawal reflex latency when administered locally by producing a block of the palmar and metacarpal nerves. Significant analgesia lasted 90 min and 210 min for procaine and mepivacaine, respectively. Phenylbutazone (7.3 mg/kg) failed to alter pain thresholds measured over a 36 h post-treatment period. However, pain thresholds rose over time with successive trials. These data suggest that in the equine (1) phenylbutazone does not alter normal cutaneous pain perception, and (2) successive presentation of painful stimuli increases nociceptive thresholds.     

Acetazolamide attenuates chemical-stimulated but not thermal-stimulated acute pain in mice

Aim： Acetazolamide （AZA）, a carbonic anhydrase （CA） inhibitor, has been found to alleviate inflammatory and neuropathic pain in rats. In the present study, we investigated the effects of AZA on thermal- and chemical-stimulated acute pain in mice and the possible mechanisms underlying the effects.
Methods： Five acute pain models based on thermal and chemical stimuli were established to investigate the effects of AZA on different types of nociception in mice. The antinociceptive effects of methazolamide （another CA inhibitor） and diazepam （a positive allosteric modulator of GABAA receptor） were also examined. The drugs were administered either intraperitoneally （ip） or intrathecally.

Results： AZA （50–200 mg/kg, ip） did not produce analgesia in two thermal-stimulated acute pain models, ie, mouse tail-flick and hot-plate tests. In contrast, AZA （50–200 mg/kg, ip） dose-dependently reduced paw licking time in both capsaicin and formalin tests in mice. A similar result was observed in a mouse acetic acid-induced writhing test. However, AZA （10 nmol/mouse, intrathecally） did not produce significant analgesia in the 3 chemical-stimulated acute pain models. In addition, methazolamide （50–200 mg/kg, ip） and diazepam （0.25–1.0 mg/kg, ip） did not produce significant analgesia in either thermal- or chemical-stimulated acute pain.

Conclusion： AZA produces analgesia in chemical-stimulated, but not thermal-stimulated acute pain in mice. The attenuation of chemical-stimulated acute pain by AZA may not be due to enhancement of GABAA receptor-mediated inhibition via inhibiting CA activity but rather a peripheral ion channel-related mechanism.     

The novel analgesic, F 13640, produces intra- and postoperative analgesia in a rat model of surgical pain

F 13640 is a newly discovered high-efficacy 5-HT(1A) receptor agonist that produces exceptional analgesia in animal models of tonic and chronic, nociceptive and neuropathic pains by novel molecular and neuroadaptive mechanisms. Here we examined the effects of F 13640 and remifentanil (0.63 mg/kg with either compound) when injected i.p. either before or 15 min after rats underwent orthopedic surgery. Surgery consisted of the drilling of a hole in the calcaneus bone and of an incision of the skin, fascia and plantar muscle of one foot. During surgery, the concentration of volatile isoflurane was progressively incremented depending on the animal's response to surgical maneuvers. Other experiments examined the dose-dependent effects of F 13640 (0.04 to 0.63 mg/kg) on surgical pain as well as on the Minimum Alveolar Concentration of isoflurane. Both F 13640 and remifentanil markedly reduced the intra-operative isoflurane requirement. F 13640 also reduced measures of postoperative pain (i.e., paw elevation and flexion). With these postoperative measures, remifentanil produced short-lived analgesia followed by hyperalgesia. F 13640 significantly reduced both surgical pain and the isoflurane Minimum Alveolar Concentration from 0.16 mg/kg onward. F 13640 produced powerful intra- and postoperative analgesia in rats undergoing orthopedic surgery. Unlike the opioid, remifentanil, F 13640 caused no hyperalgesia with ongoing postoperative pain, and should remain effective with protracted postoperative use.     

Involvement of serotoninergic mechanism in analgesia by castration and flutamide, a testosterone antagonist, in the rat formalin test

Several studies have suggested that testosterone has a role in nociception. Recently, we have shown that castration and flutamide, a testosterone antagonist, induce analgesia in the late phase of formalin test, which is related to increase of 5-HT levels in the dorsal horn of the lumbar spinal cord. The aim of the present study was to investigate the effect of fluoxetine, a selective serotonin reuptake inhibitor, on castration and flutamide-induced analgesia in order to further explore the role of 5-HT systems in such analgesia. Four weeks after castration, there was an analgesia in the late phase of formalin test, and this was potentiated by acute (0.32 mg kg(-1) ip) treatment of fluoxetine. Furthermore, coadministration of fluoxetine (0.32 mg kg(-1) ip) and flutamide (10 mg kg(-1) ip) produced more antinociceptive effect than those animals receiving fluoxetine and flutamide alone. The analgesic effect of fluoxetine (0.32 mg kg(-1) ip) and flutamide (10 mg kg(-1) ip) was abolished by pretreatment with 5,7-DHT (100 microg/rat it) and naloxone (2 mg kg(-1) ip). In summary, our data suggest that fluoxetine and flutamide have antinociceptive effects in tonic inflammatory pain through functional alteration of serotonergic systems, and their effects are potentiated by coadministration. The possible role of opioidergic system in their antinociceptive effect cannot be neglected.     

Different mechanisms underlie the analgesic actions of paracetamol and dipyrone in a rat model of inflammatory pain

BACKGROUND AND PURPOSE: The analgesics, paracetamol and dipyrone are weak inhibitors of the cyclooxygenase isoforms 1 or 2 (COX-1, COX-2) but more potent on COX-3. Both are also weak anti-inflammatory agents, relative to their analgesic and antipyretic activities. In a model of inflammatory pain mediated by prostaglandins, both compounds were analgesic. We have analysed this shared effect further in order to elucidate the underlying mechanisms.EXPERIMENTAL APPROACH: Inflammation was induced in one hind paw of rats by intraplantar injection of 250 microg lambda-carrageenan (CG) and the contralateral paw injected with saline. Nociceptive thresholds to mechanical stimulation were measured immediately before and for 6 h after, injection of CG. The analgesics were s.c. or locally (intraplantar) injected either 30 min before or 2 h after CG. In some groups, naltrexone was injected (s.c. or intraplantar), 1 h before CG. KEY RESULTS: Pretreatment with paracetamol or dipyrone (60-360 mg kg(-1)) reversed hyperalgesia induced by CG and increased nociceptive threshold in the inflamed paw above the basal level (hypoalgesia). Paracetamol, but not dipyrone, also raised nociceptive thresholds in the non-inflamed paw. Subcutaneous, but not local, administration of naltrexone, a specific opioid antagonist, reversed the hypoalgesia induced by paracetamol, but similar naltrexone treatment had no effect on dipyrone-induced analgesia.CONCLUSIONS AND IMPLICATIONS: Although both paracetamol and dipyrone are inhibitors of COX isoforms and thus of prostaglandin biosynthesis and were analgesic in our model, their analgesic actions were functionally and mechanistically different. Satisfactory mechanisms of action for these analgesics still remain to be established.     

侧脑室或鞘内注射烟碱对恩氟烷催眠和镇痛作用的影响

目的初步分析恩氟烷的催眠和镇痛作用与神经元烟碱受体之间的关系。方法催醒实验:小鼠ip恩氟烷2.2mL.kg-1,翻正反射消失1min后,分别脑室注射烟碱10,20和40μg(5μL),记录翻正反射恢复时间(即睡眠时间)。镇痛实验:①甲醛实验:小鼠ip恩氟烷0.5mL.kg-1,5min后分别鞘内注射烟碱5,10和15μg(5μL),再5min后于足底皮下注射2%甲醛溶液20μL,记录60min内小鼠舔被注射足的累积时间。②热板实验:给药方法同甲醛实验,于注射烟碱后5,10,15,20和25min记录小鼠足部接触热板至开始添后足的时间作为后足痛阈。结果脑室注射烟碱能明显减少恩氟烷催眠小鼠的睡眠时间;鞘内注射烟碱不能拮抗甲醛实验中恩氟烷的镇痛作用,但可拮抗热板实验中恩氟烷的镇痛作用。结论神经元烟碱受体可能是恩氟烷催眠作用的重要靶位之一;也可能是恩氟烷对热刺激镇痛作用的重要靶位之一,而非对化学、炎性刺激镇痛作用的靶位。     

Nefopam reduces thermal hypersensitivity in acute and postoperative pain models in the rat

The activity of nefopam, a centrally acting compound, not structurally related to other analgesics, was examined in acute and postoperative thermal pain models in the rat. Its antinociceptive potency was evaluated using heat noxious stimuli either in intact or in injured animals after skin and muscular incisions. In the hot plate and in the plantar tests, nefopam after acute administration by different routes exhibited a dose-dependent attenuation of the nociceptive responses at 10-30 mg x kg(-1) by intraperitoneal or subcutaneous administration, at 60 mg x kg(-1) by oral dosing, and from 3 mg x kg(-1) after intravenous injection. In the postoperative pain model, at 30 mg x kg(-1) nefopam augmented the endpoint to thermal threshold, 60 and 90 minutes after administration compared to the threshold recorded after the incision. In the same conditions, morphine and tramadol displayed antinociceptive activities. As the plantar test provides a good index of nociception in humans, these results point out the usefulness of nefopam for attenuating moderate to severe pain, and for postoperative analgesia. In conclusion, nefopam has shown potent properties to reduce thermal hypersensitivity after acute or postoperative pain in rats.     

Effect of intraarticular tramadol administration in the rat model of knee joint inflammation

Local administration of exogenous opioids may cause effective analgesia without adverse symptoms from the central nervous system. Experiments show that peripheral antinociceptive effect of opioids is observed especially in inflammatory pain. The aim of the research was to estimate the effect of tramadol on nociceptive process at the level of peripheral nervous system, after its local administration in the model of knee joint inflammation. Tramadol was administered intraarticulary into the rat knee joint, before the inflammation as a preemptive analgesia and, for comparison, after the intraarticular injection of carrageenan. The research determined the influence of tramadol injection on pain threshold for thermal stimuli, development of inflammatory processes using the measurement of joint edema and motor function following the induction of knee joint inflammation in the rat. Functional assessment of knee joint with inflammation, in terms of rats' mobility and body position as well as joint loading and mobility were studied. The results of the experiments show that local administration of tramadol induces antinociceptive effect. The effect of tramadol, which elicits also a decrease in inflammatory edema, appears not only after its administration after carrageenan when inflammation was already present, but also in the case of its injection prior to carrageenan in the scheme of preemptive analgesia. The results of the described research show that not only morphine but also another opioid, tramadol, widely used in clinical practice, inhibits nociception, edema and functional impairment of the paw after its local application directly to the inflamed knee joint.     

Profound,non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain

Previously, we have reported that in rat models of chronic pain, in particular, the very-high-efficacy 5-HT(1A) agonist F 13640 induces unprecedented pain relief by novel neuroadaptative mechanisms that involve inverse tolerance and cooperation with nociceptive stimulation in producing analgesia. The present studies detailed the actions of F 13640 and other compounds in the formalin model of tonic nociceptive pain. Intraperitoneal injection of F 13640 (0.01-2.5 mg/kg; t -15 min) caused a dose-dependent and complete inhibition of the paw elevation and paw licking that occurred both early (0-5 min) and late (22.5-27.5 min) after the intraplantar injection of diluted formaldehyde (2.5%) in the rat. The extent to which F 13640 and other 5-HT(1A) receptor ligands inhibited these pain behaviors correlated (p < 0.05) with the extent to which they activated 5-HT(1A) receptors. Under similar conditions, some inhibitory effects were also observed with various agents that are known to produce analgesia by different peripheral and/or central mechanisms (e.g., opioids, NA/5-HT reuptake inhibitors, COX-2 inhibitors and other nonsteroidal anti-inflammatory drugs, gabapentin, and ABT-594). However, with the possible exception of morphine, the effects of all of these agents at nontoxic doses were lower than those of F 13640, in particular in inhibition of early paw elevation. The 5-HT(1A) antagonist WAY 100635, but not naloxone, antagonized the actions of F 13640. These results help to establish large-magnitude 5-HT(1A) receptor activation as a new molecular mechanism of profound, central analgesia and suggest that F 13640 may be particularly effective against pain arising from severe tonic nociceptive stimulation.     

地佐辛复合地塞米松超前镇痛在儿童腺样体摘除术中的应用

目的探讨地佐辛复合地塞米松在儿童鼻内镜腺样体摘除术中超前镇痛的临床效果。方法将2011年1月至2012年6月收住入院待手术的60例腺样体肥大患儿随机分为A、B、C三组,每组20例,A组为超前镇痛组,术前静脉注射地佐辛0.1 mg/kg、地塞米松5 mg,术毕注射生理盐水2 mL;B组为术后镇痛组,术前静脉注射生理盐水2 mL,术毕注射地佐辛0.1 mg/kg、地塞米松5 mg;C组为对照组,术前、术后各静脉注射生理盐水2 mL。观察并记录三组诱导前、拔管时、拔管后5 min平均动脉压（MAP）、心率（HR）;苏醒拔管时间,苏醒期患儿有无躁动呛咳;术后0.5、1、2、4、6、12、24 h的视觉模拟评分（VAS评分）及各种不良反应的发生率。结果 C组患儿MAP、HR拔管时、拔管后均高于诱导前,且高于A、B组拔管时、拔管后,差异有统计学意义（P〈0.01）,C组患儿苏醒期躁动呛咳明显高于A、B组,差异有统计学意义（P〈0.01）,术后0.5、1、2、4、6、12、24 h的VAS评分及恶心、呕吐发生率均明显高于A、B组,差异有统计学意义（P〈0.05）,B组苏醒拔管时间大于A、C组,差异有统计学意义（P〈0.05）,A组术后4、6、12、24 h的VAS评分明显小于B组,差异有统计学意义（P〈0.05）。结论地佐辛、地塞米松复合液超前镇痛在儿童鼻内镜腺样体摘除术中具有协同作用,能延长术后镇痛的时间,降低恶心、呕吐发生率,且术后苏醒迅速、安全。     

Involvement of cholinergic system in suppression of formalin-induced inflammatory pain by cobratoxin

Aim:

To investigate the analgesic effect of cobratoxin (CTX), a long-chain α-neurotoxin from Thailand cobra venom, in a rat model of formalin-induced inflammatory pain.

Methods:

Inflammatory pain was induced in SD rats via injecting 5% formalin (50 μL) into the plantar surface of their right hind paw. CTX and other agents were ip administered before formalin injection. The time that the animals spent for licking the injected paw was counted every 5 min for 1 h.

Results:

CTX (25, 34, and 45 μg/kg) exhibited a dose-dependent analgesic effect during the phase 1 (0–15 min) and phase 2 (20–60 min) response induced by formalin. Pretreatment with naloxone (0.5 or 2.5 mg/kg) did not block the analgesic effect of CTX. Pretreatment with atropine at 5 mg/kg, but not at 2.5 mg/kg, antagonized the analgesic effect of CTX. Treatment with the nonselective nAChR antagonist mecamylamine (3 mg/kg) inhibited the analgesic effects of CTX in Phase 1 and Phase 2 responses, while with the selective α7-nAChR antagonist methyllycaconitine (3 mg/kg) antagonized the effect of CTX only in the Phase 1 response. Treatment with the α7-nAChR agonist PNU282987 (3 mg/kg) significantly reduced the formalin-induced phase 2 pain response, but only slightly reduced the Phase 1 pain response.

Conclusion:

The results suggest that CTX exerts an antinociceptive effect in formalin-induced inflammatory pain, which appears to be mediated by mAChR and α7-nAChR.     

Modulation of BzATP and formalin induced nociception: attenuation by the P2X receptor antagonist, TNP-ATP and enhancement by the P2X(3) allosteric modulator, cibacron blue

1. Exogenous ATP produces acute and localized pain in humans, and P2X receptor agonists elicit acute nociceptive behaviours in rodents following intradermal administration to the hindpaw. The predominant localization of P2X(3) mRNA in sensory neurones has led to the hypothesis that activation of P2X(3) and/or P2X(2/3) receptors contributes to nociception. 2. The local administration of the P2X receptor agonist, BzATP (100--1000 nmol paw(-1), s.c.) into the rat hindpaw produced an acute (<15 min) paw flinching response that was similar to that observed in the acute phase of the formalin (5%) test. 3. The co-administration of the potent P2X receptor antagonist, TNP-ATP (30--300 nmol paw(-1)), but not an inactive analogue, TNP-AMP, with BzATP into the rat hindpaw attenuated BzATP-induced nociception. Similarly, co-administration of TNP-ATP, but not TNP-AMP, with 5% formalin reduced both acute and persistent nociception in this test. 4. Co-administration of cibacron blue (30 and 100 nmol paw(-1)), a selective allosteric enhancer of P2X(3) and P2X(2/3) receptor activation, with BzATP (30 and 100 nmol paw(-1)) into the rat hindpaw produced significantly greater nociception as compared to the algogenic effects of BzATP alone. Intradermal co-administration of cibacron blue (30 and 100 nmol paw(-1)) with formalin (1 and 2.5%) into the rat hindpaw also produced significantly greater nociceptive behaviour as compared to formalin alone. 5. The ability of TNP-ATP and cibacron blue to respectively attenuate and enhance nociceptive responses elicited by exogenous BzATP and formalin provide further support for the hypothesis that activation of peripheral P2X(3) containing channels contributes specifically to both acute and persistent nociception in the rat.