Liposome-encapsulated oxymorphone hydrochloride provides prolonged relief of postsurgical visceral pain in rats

Adequate pain control is necessary for optimal postsurgical recovery and humane treatment of laboratory and companion animals. Opioid drugs are currently the most potent analgesic agents available in human and veterinary medicine. Long-acting formulations of opioid drugs confer several important advantages over standard pharmaceutical preparations, especially for use in animals. A long-acting formulation of oxymorphone hydrochloride was produced by encapsulation into liposomes. Liposome-encapsulated (LE) oxymorphone was tested in a rat model of visceral postoperative pain. Rats were given one subcutaneous injection of LE oxymorphone (1.2 or 1.6 mg/kg of body weight) or standard oxymorphone (0.3 mg/kg) at the time of intestinal transection or resection. A single administration of LE oxymorphone hydrochloride was as effective for relief of postoperative pain in rats (P = 0.18), as were multiple (q4 h or q8 h) injections of 0.3 mg/kg of the standard pharmaceutical preparation. The rats given LE oxymorphone prior to intestinal resection also had significantly higher body weight at three and seven days after surgery than did rats that were given standard oxymorphone. In conclusion, LE oxymorphone was effective in treating visceral pain associated with intestinal surgery in rats. On the basis of body weight gain, rats treated with LE oxymorphone had improved recovery outcome, compared with rats treated with repeated injections of standard oxymorphone.     

"Anxiebo", placebo, and postoperative pain

Background

Surgical treatment and its consequences expose patients to stress, and here we investigated the importance of the psychological component of postoperative pain based on reports in the clinical literature.

Discussion

Postoperative pain remains a significant clinical problem. Increased pain intensity with increased demand for opioid medication, and/or a relative unresponsiveness to pain treatment was reported both when the analgesia was administered by means of conventional nurse injection regimes and patient-controlled analgesia (PCA). Both the quality of the analgesia, and the sensitivity of postoperative models for assessing analgesic efficacy could be significantly influenced. The findings could be explained by increased penetration of an algesic anxiety-related nocebo influence (which we chose to call "anxiebo") relative to its analgesic placebo counterpart. To counteract this influence, the importance of psychological effects must be acknowledged, and doctors and attending nurses should focus on maintaining trustful therapist-patient relationships throughout the treatment period. The physical mechanism of anxiebo should be further explored, and those at risk for anxiebo better characterized. In addition, future systemic analgesic therapies should be directed towards being prophylactic and continuous to eliminate surgical pain as it appears in order to prevent the anxiebo effect. Addressing anxiebo is the key to developing reproducible models for measuring pain in the postoperative setting, and to improving the accuracy of measurements of the minimum effective analgesic concentration.

Summary

Anxiebo and placebo act as counterparts postoperatively. The anxiebo state may impair clinical analgesia and reduce the sensitivity of analgesic trials. Ways to minimize anxiebo are discussed.     

Are repeated doses of buprenorphine detrimental to postoperative recovery after laparotomy in rats?

Buprenorphine is a widely used analgesic for relief of postoperative pain in rats. The effect of repeated doses of buprenorphine throughout the postoperative pain and stress response is unknown. This investigation tested the hypotheses that (a) daily analgesic doses of buprenorphine for 7 d ameliorate the stress response after laparotomy in rats and (b) preoperative buprenorphine better ameliorates the response than do peri- and postoperative administration. Postoperative effects on body weight, daily food and water consumption, and daily fecal and urinary outputs were monitored in groups of rats treated for 7 d with analgesic doses of buprenorphine initiated at different time points relative to the time of laparotomy. Analgesic doses of buprenorphine had no effect on the study parameters in healthy unoperated rats. Daily injection of buprenorphine delayed the time at which the preoperative body weight was restored without decreasing the postoperative changes in daily food consumption, water intake, and fecal and urinary outputs in the operated rats. The effects of daily analgesic doses of buprenorphine for 7 d on body weight, daily food, and water consumption, and fecal and urinary outputs were minimal and less statistically significant than the changes caused by surgery itself. However, this dosing regimen seems to delay the restoration of body weight after abdominal surgery in rats.     

Analysis of the analgesic effects of tricyclic antidepressants on neuropathic pain,diabetic neuropathic pain,and fibromyalgia in rat models

ObjectiveTo investigate the analgesic effect of amitriptyline on neuropathic pain model rats, diabetic neuropathic pain model rats and fibromyalgia model rats.MethodsThe healthy male Sprague wrote – Dawley (SD) rats were taken as the research object, and they were randomly divided into model group (group A), beside the sciatic nerve and injection of 5 mm amitriptyline group (group B), beside the sciatic nerve and injection of 10 mm amitriptyline group (group C), beside the sciatic nerve and injection of 15 mm amitriptyline group (group D), intraperitoneal injection of amitriptyline group (group E). Pain induced by selective injury of sciatic nerve branches in rats, pain induced by chronic compression of sciatic nerve, diabetic neuropathic pain and fibromyalgia were conducted to determine the pain threshold of mechanical stimulation in rats after drug administration.ResultsThe pain threshold of mechanical stimulation in the local amitriptyline group (group B, C, D) was significantly higher than that in the group A and group E at each time point after drug treatment, and the pain threshold of mechanical stimulation gradually increased with the increase of concentration. There was no statistically significant difference in mechanical stimulation pain threshold between group A and group E at each time point after drug treatment.ConclusionPara-sciatic injection of amitriptyline at different concentrations has analgesic effects on neuropathic pain, diabetic neuropathic pain and fibromyalgia in rat models, and amitriptyline directly ACTS on the local sciatic nerve.     

Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure

Background

Gabapentin is an antiepileptic drug used in a variety of chronic pain conditions. Increasing numbers of randomized trials indicate that gabapentin is effective as a postoperative analgesic. This procedure-specific systematic review aims to analyse the 24-hour postoperative effect of gabapentin on acute pain in adults.

Methods

Medline, The Cochrane Library and Google Scholar were searched for double-blind randomized placebo controlled trials of gabapentin for postoperative pain relief compared with placebo, in adults undergoing a surgical procedure. Qualitative analysis of postoperative effectiveness was evaluated by assessment of significant difference (P < 0.05) in pain relief using consumption of supplemental analgesic and pain scores between study groups. Quantitative analyses of combined data from similar procedures, were performed by calculating the weighted mean difference (WMD) of 24-hour cumulated opioid requirements, and the WMD for visual analogue scale (VAS) pain, (early (6 h) and late (24 h) postoperatively), between study groups. Side-effects (nausea, vomiting, dizziness and sedation) were extracted for calculation of their relative risk (RR).

Results

Twenty-three trials with 1529 patients were included. In 12 of 16 studies with data on postoperative opioid requirement, the reported 24-hour opioid consumption was significantly reduced with gabapentin. Quantitative analysis of five trials in abdominal hysterectomy showed a significant reduction in morphine consumption (WMD – 13 mg, 95% confidence interval (CI) -19 to -8 mg), and in early pain scores at rest (WMD – 11 mm on the VAS, 95% CI -12 to -2 mm) and during activity (WMD -8 mm on the VAS; 95% CI -13 to -3 mm), favouring gabapentin. In spinal surgery, (4 trials), analyses demonstrated a significant reduction in morphine consumption (WMD of – 31 mg (95%CI – 53 to -10 mg) and pain scores, early (WMD – 17 mm on the VAS; 95 % CI -31 to -3 mm) and late (WMD -12 mm on the VAS; 95% CI -23 to -1 mm) also favouring gabapentin treatment. Nausea was improved with gabapentin in abdominal hysterectomy (RR 0.7; 95 % CI 0.5 to 0.9). Other side-effects were unaffected.

Conclusion

Perioperative use of gabapentin has a significant 24-hour opioid sparing effect and improves pain score for both abdominal hysterectomy and spinal surgery. Nausea may be reduced in abdominal hysterectomy.     

Multimodal analgesia protocol for pain management after total knee arthroplasty: comparison of three different regional analgesic techniques

Objectives:To evaluate three different analgesic techniques, continuous epidural analgesia (EA), continuous intra-articular (IA) infusion analgesia and continuous femoral nerve block (FNB) in postoperative pain management, length of hospital stay (LOS), and time of patient mobilization after total knee arthroplasty (TKA).Methods:Seventy-two patients undergoing TKA were randomly allocated into three groups according to the analgesic technique used for postoperative pain management. Group EA patients received epidural analgesia (control group), group IA received intra-articular infusion and group FNB received femoral nerve block.Results:Upon analyzing the Numerical Rating Scale (NRS) scores at rest, at passive and active movement, up to 3 days postoperatively, we observed no statistically significant differences at any time point among the three groups. Similarly, no association among these analgesic techniques (EA, IA, FNB) was revealed regarding LOS. However, significant differences emerged concerning the time of mobilization. Patients who received IA achieved earlier mobilization compared to FNB and EA.Conclusions:Both IA and FNB generate similar analgesic effect with EA for postoperative pain management after TKA. However, IA appears to be significantly more effective in early mobilization compared to EA and FNB. Finally, no clinically important differences could be detected regarding LOS among the techniques studied.     

The assessment of post-vasectomy pain in mice using behaviour and the Mouse Grimace Scale

Background

Current behaviour-based pain assessments for laboratory rodents have significant limitations. Assessment of facial expression changes, as a novel means of pain scoring, may overcome some of these limitations. The Mouse Grimace Scale appears to offer a means of assessing post-operative pain in mice that is as effective as manual behavioural-based scoring, without the limitations of such schemes. Effective assessment of post-operative pain is not only critical for animal welfare, but also the validity of science using animal models.

Methodology/Principal Findings

This study compared changes in behaviour assessed using both an automated system (“HomeCageScan”) and using manual analysis with changes in facial expressions assessed using the Mouse Grimace Scale (MGS). Mice (n = 6/group) were assessed before and after surgery (scrotal approach vasectomy) and either received saline, meloxicam or bupivacaine. Both the MGS and manual scoring of pain behaviours identified clear differences between the pre and post surgery periods and between those animals receiving analgesia (20 mg/kg meloxicam or 5 mg/kg bupivacaine) or saline post-operatively. Both of these assessments were highly correlated with those showing high MGS scores also exhibiting high frequencies of pain behaviours. Automated behavioural analysis in contrast was only able to detect differences between the pre and post surgery periods.

Conclusions

In conclusion, both the Mouse Grimace Scale and manual scoring of pain behaviours are assessing the presence of post-surgical pain, whereas automated behavioural analysis could be detecting surgical stress and/or post-surgical pain. This study suggests that the Mouse Grimace Scale could prove to be a quick and easy means of assessing post-surgical pain, and the efficacy of analgesic treatment in mice that overcomes some of the limitations of behaviour-based assessment schemes.     

Analgesic efficacy of orally administered buprenorphine in rats: methodologic considerations

Buprenorphine has been widely recommended for treatment of pain in rodents. We have previously documented that the recommended postoperative oral dose of buprenorphine in male Long-Evans rats, 0.5 mg/kg, is not as effective as the recommended parenteral dose of buprenorphine (0.05 mg/kg, s.c.) as an analgesic. In the series of experiments reported here, we compared: the analgesic effect of buprenorphine when prepared in two ways in the laboratory with that of a commercially available injectable solution of buprenorphine; the analgesic effect of buprenorphine in Long-Evans rats with that in Sprague-Dawley rats; and Long-Evans and Sprague-Dawley rats for development of pica, a commonly reported side effect of buprenorphine. We followed the pica experiment with assessment of the effectiveness of buprenorphine in establishing a conditioned flavor aversion. The results indicated that method of preparation did not result in any significant differences in the efficacy of injected buprenorphine. Strain of rat was not associated with a significant difference in the efficacy of buprenorphine. However, a significant strain difference was found in development of pica. Buprenorphine treatment was effective in inducing a conditioned flavor aversion. We concluded that the recommended oral dose of buprenorphine (0.5 mg/kg) is ineffective as an analgesic, and that this was not the result of method of preparation of the buprenorphine or strain of rat used. Furthermore, we concluded that buprenorphine treatment may induce gastrointestinal distress in both strains tested. The results reaffirm our previous conclusion that oral administration of buprenorphine at 0.5 mg/kg, despite the general recommendation, is not a reasonable treatment for postsurgical pain in rats.     

A randomized,placebo controlled,trial of preoperative sustained release Betamethasone plus non-controlled intraoperative Ketorolac or Fentanyl on pain after diagnostic laparoscopy or laparoscopic tubal ligation [ISRCTN52633712

BACKGROUND: Gynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain. METHODS: This study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone trade mark ) or an optically identical placebo injection of Intralipid trade mark and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined. RESULTS: Although the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056) in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative period. Intraoperative ketorolac treatment significantly lowered (P = 0.027) pain scores and reduced the postoperative requirement for additional pain relief drugs. CONCLUSIONS: There was a lack of efficacy of preoperative sustained release betamethasone in reducing postoperative pain despite maintaining a therapeutic concentration during the postoperative period. Intraoperative Ketorolac did afford some short-term pain relief in the postoperative period and reduced the need for additional pain relief drugs.     

椎体成形术治疗脊柱压缩骨折的临床疗效

目的:探讨脊柱压缩骨折患者的椎体成形术应用方法与效果。方法:脊柱压缩骨折患者150例根据随机抽签法分为治疗组与对照组各75例,对照组给予传统开放性手术,治疗组给予椎体成形术。通过比较两组手术时间,术中出血量,术后住院时间,术后疼痛评分,术后局部Cobb角的差异评价治疗效果,其中,疼痛评分采用VAS量表,局部Cobb角通过脊椎侧围X片测定。结果:所有患者都顺利完成手术,无严重并发症发生,治疗组的术中出血量与术后住院时间明显少于对照组(P0.05)。两组术前疼痛评分对比差异无统计学意义,术后疼痛评分都呈现明显下降的趋势(P0.05),同时术后治疗组的疼痛评分明显低于对照组(P0.05)。两组术前局部Cobb角对比差异无统计学意义,术后局部Cobb角都明显下降(P0.05),同时术后治疗组的局部Cobb角都明显低于对照组(P0.05)。结论:脊柱压缩骨折患者的椎体成形术应用能有效缓解疼痛程度,改善椎体前中部高度脊柱后凸情况,对于患者的创伤比较少,有很好的推广应用价值。     

The effectiveness of surgical and nonsurgical interventions in relieving the symptoms of macromastia

In this report, the authors evaluate the effectiveness of breast reduction in alleviating the symptoms of macromastia by comparing baseline and postoperative health status using a series of well-validated self-report instruments. The study had a prospective design with a surgical intervention group and two control groups: a hypertrophy control group with bra cup sizes D or larger and a normal control group with bra cup sizes less than D. The effectiveness of nonsurgical interventions in relieving the symptoms of macromastia was also evaluated, both in the operative subjects and in the control groups.Surgical candidates and controls completed a self-administered baseline survey that consisted of the following validated and standardized instruments commonly used to evaluate outcomes: SF-36, EuroQol, Multidimensional Body-Self Relations Questionnaire (MBSRQ), and the McGill Pain Questionnaire (MPQ). A specially designed and validated instrument, the Breast-Related Symptoms (BRS), was also used. There were also questions about prior nonsurgical treatments, comorbid conditions, bra size, and a physical assessment. Additional information obtained on the operative subjects included surgical procedure data, resection weight, and complications. Approximately 6 to 9 months postoperatively, surgical subjects completed the same questionnaire as described above, and a final physical assessment was performed.The cohort included 179 operative subjects with matched preoperative and postoperative data sets, 96 normal controls and 88 hypertrophy controls. The women were predominantly Caucasian, middle-aged, well educated, and employed. Fifty percent of the operative subjects reported breast-related pain all or most of the time in the upper back, shoulders, neck, and lower back preoperatively compared with less than 10 percent postoperatively. Operative subjects and hypertrophy controls tried a number of conservative treatments, including weight loss, but none provided adequate permanent relief. Compared with population norms, the preoperative subjects had significantly lower scores (p < 0.05) in all eight health domains of the SF-36, and in the mental and physical component summary scores. After surgery, the operative subjects had higher means (better health) than national norms in seven of the eight domains and improved significantly from presurgical means in all eight domains (p < 0.05). Before surgery, the operative subjects reported high levels of pain with a Pain Rating Index (PRI) score from the MPQ of 26.6. After surgery, pain was significantly lower with a mean PRI score of 11.7, similar to that of our controls (mean PRI score, 11.2). Regression analysis was used to control for covariate effects on the main study outcomes. Among the operative subjects, benefits from breast reduction were not associated with body weight, bra cup size, or weight of resection, with essentially all patients benefiting from surgery.Breast hypertrophy has a significant impact on women's health status and quality of life as measured by validated and widely used self-report instruments including the SF-36, MPQ, and EuroQol. Pain is a significant symptom in this disease, and both pain and overall health status are markedly improved by breast reduction. In this population, conservative measures such as weight loss, physical therapy, special brassieres, and medications did not provide effective permanent relief of symptoms.     

Overexpression of RAPGEF3 enhances the therapeutic effect of dezocine in treatment of neuropathic pain

Pain is a significant problem worldwide that affects the quality of life of patients. Dezocine is a non-addictive analgesic drug with kappa-opioid antagonist activity and has been successfully used to alleviate of postoperative pain. In addition, dezocine has an analgesic effect similar to that of morphine, alleviating moderate to severe pain. Rap guanine nucleotide exchange factor 3 (RAPGEF3) is a guanine nucleotide exchange factor for GTPases Rap1 and Rap2, which could enhance the activity of Rap1 to promote cell adhesion and axon regeneration, as well as promote neurite extension by interacting with nerve growth factors. Here, we first observed that overexpression of RAPGEF3 increased cell viability, as shown by a CCK-8 assay, and recovered brain function in rats. The expression of inflammation-related factors at the mRNA level was detected using qPCR, and the concentration of these factors in a cultured cell medium and rat serum samples were decreased as shown by ELISA after RAPGEF3 overexpression. Through western blotting, we further found that pro-inflammatory proteins were decreased, and these effects might be mediated by inhibition of the Ras/p-38 MAPK signaling pathway. Taken together, we speculated that RAPGEF3overexpression enhances the therapeutic effect of dezocine on neuropathic pain by inhibiting the inflammatory response through inhibition of the Ras/p-38 MAPK signaling pathway.Keywords: RAPGEF3, dezocine, neuropathic pain, Ras/p-38 MAPK, inflammation     

The relation between the effect of a subhypnotic dose of thiopental on claw pain threshold in rats and adrenalin,noradrenalin and dopamine levels

Thiopental sodium (TPS) needs to be applied together with adrenalin in order to establish its analgesic effect in general anesthesia. We aimed to investigate the effect of TPS on the claw pain threshold in rats and evaluated its relationship with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels. Intact and adrenalectomized rats were used in the experiment. Intact animals were divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and 0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP levels were measured. The TS group’s claw pain threshold was found low. However, the claw pain thresholds of the ATS and ADR groups increased significantly. In the A-TS group, the pain threshold decreased compared with normal, and in the A-ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR levels in intact rats; however, no significant changes were observed in the NDR and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in rats. The present study shows that to achieve analgesic activity, TPS needs to be applied together with ADR.     

Comparative effect of intraoperative propacetamol versus placebo on morphine consumption after elective reduction mammoplasty under remifentanil-based anesthesia: a randomized control trial [ISRCTN71723173]

BACKGROUND: Postoperative administration of paracetamol or its prodrug propacetamol has been shown to decrease pain with a morphine sparing effect. However, the effect of propacetamol administered intra-operatively on post-operative pain and early postoperative morphine consumption has not been clearly evaluated. In order to evaluate the effectiveness of analgesic protocols in the management of post-operative pain, a standardized anesthesia protocol without long-acting opioids is crucial. Thus, for ethical reasons, the surgical procedure under general anesthesia with remifentanil as the only intraoperative analgesic must be associated with a moderate predictable postoperative pain. METHODS: We were interested in determining the postoperative effect of propacetamol administered intraoperatively after intraoperative remifentanil. Thirty-six adult women undergoing mammoplasty with remifentanil-based anesthesia were randomly assigned to receive propacetamol 2 g or placebo one hour before the end of surgery. After remifentanil interruption and tracheal extubation in recovery room, pain was assessed and intravenous titrated morphine was given. The primary end-point was the cumulative dose of morphine administered in the recovery room. The secondary end-points were the pain score after tracheal extubation and one hour after, the delay for obtaining a Simplified Numerical Pain Scale (SNPS) less than 4, and the incidence of morphine side effects in the recovery room.For intergroup comparisons, categorical variables were compared using the chi-squared test and continuous variables were compared using the Student t test or Mann-Whitney U test, as appropriate. A p value less than 0.05 was considered as significant. RESULTS: In recovery room, morphine consumption was lower in the propacetamol group than in the placebo group (p = 0.01). Pain scores were similar in both groups after tracheal extubation and lower in the propacetamol group (p = 0.003) one hour after tracheal extubation. The time to reach a SNPS < 4 was significantly shorter in the propacetamol group (p = 0.02). The incidence of morphine related side effects did not differ between the two groups. CONCLUSIONS: Intraoperative propacetamol administration with remifentanil based-anesthesia improved significantly early postoperative pain by sparing morphine and shortening the delay to achieve pain relief.     

剑突肋缘下三孔式胸腔镜下胸腺切除治疗重症肌无力的早期临床疗效及对生活质量的影响

目的:通过与传统单侧胸腔镜技术对比,探讨经剑突肋缘下三孔式胸腔镜下胸腺切除治疗重症肌无力的早期临床疗效及对患者生活质量的影响。方法:收集2012年1月-2016年6月因重症肌无力就诊于我院行胸腔镜下胸腺切除的115例患者。根据患者的手术方式分为传统单侧胸腔镜组47例和剑突肋缘下三孔式胸腔镜组68例,收集和比较两组患者的基本资料,包括性别、年龄、是否合并胸腺瘤、病程、随访时间、术前Osserman评分、手术时间、术中出血量、术后引流时间、术后引流量、转入ICU时间、术后住院时间、术后并发症的发生情况、术后不同时间点的疼痛评分和生活质量评分及末次随访时的愈后情况。结果:两组患者的年龄、性别比例、胸腺瘤情况、病程、随访时间和术前Osserman评分均没有差异(P0.05)。三孔组手术时间、术中出血量、ICU停留时间和术后住院时间均短于或低于传统组(P0.05)。两组患者术后并发症(膈神经麻痹、胸腔积液、伤口脂肪液化)发生率比较没有统计学差异(P0.05)。三孔组患者在术后3天内和出院时的疼痛评分均显著低于传统组(P0.05)。两组患者在末次随访时的有效率、术前、术后1年和末次随访时的生活质量评分(MGQOL-15评分)比较差异无统计学意义(P0.05)。在三孔组患者末次随访时,女性MGQOL-15评分改善量(11.2±3.3分)高于男性(7.4±2.7分)(P0.001)。Osserman评分3分和4分的患者MGQOL-15评分改善量(10.7±3.7分)显著高于Osserman评分2分的患者(5.0±1.9分)(P0.001)。结论:经剑突肋缘下三孔式胸腔镜下切除胸腺治疗重症肌无力具有手术时间短、术中出血少、术后恢复快的特点,术后患者疼痛程度轻,生活质量改善明显。女性术后获益较男性更大。     

Transdermal fentanyl compared with parenteral buprenorphine in post-surgical pain in swine: a case study

The use of pigs as research animals in survival surgery has increased greatly in the last 15 years. Personnel conducting pig research have been hampered by a lack of proven long-acting analgesics for treatment of surgical pain of longer duration, and by a lack of reliable non-subjective parameters for the assessment of pain relief. The efficacy of the mixed opioid agonist-antagonist buprenorphine hydrochloride 0.10 mg/kg pr (n = 2) in the treatment of post-thoracotomy pain was compared with that of a transdermal therapeutic system (TTS) delivering 25 microg/h (n = 3) or 50 microg/h (n = 2) of the mu opioid agonist fentanyl hydrochloride. Food consumption, pain score, activity level and rate of movement were assessed under four conditions: normal pre-operative control (24h), pre-operative with analgesic alone (24h) and post-operative days 1, 2, 3 (72h). Serum concentration-time curves for fentanyl in clinical cases revealed that female Yorkshire cross pigs weighing 26.2+ 2.1 kg achieved serum values in the recognized human therapeutic range when treated with TTS fentanyl at 50 microg/h and experienced adequate pain control. Pigs treated with 25 microg/h TTS fentanyl had serum levels below the human analgesic range, experienced less adequate analgesia, and required supplemental analgesia in some cases. Based on existing pharmacokinetic data for fentanyl in pigs, the rate of uptake of TTS fentanyl when attached on inter-scapular skin was lower than predicted. Clinical pain scores and time intervals between each major postural change were not affected by analgesics in the absence of pain, but increased in all groups after surgery regardless of treatment. Food consumption was unaffected by analgesic treatment alone but decreased in all groups after surgery regardless of treatment. Analgesic effects on postoperative activity level were variable. TTS fentanyl at appropriate doses is a cost effective means of delivering basal analgesia following major surgery in pigs.     

Gender differences in predator induced pain perception in rats

Pain is an unpleasant sensation. It warns the living being about the impending damage to the tissues. The perception of pain is influenced by physical and psychological factors. The impact of chronic intermittent psychological stress on pain perception and the differences in antinociceptive responses have been studied in male and anestrous female albino rats. Fifteen rats in each group were subjected to psychological stress, by exposing them to their natural predator--cat, for a duration of 20 min daily for 12 consecutive days. Tail flick response latency to radiant heat was used as a measure to evaluate pain perception. It was observed that both the groups had a relatively high pain threshold at the beginning of exposure schedule due to the modulation of opioid analgesic system by the higher level of circulating testosterone in males and low level of estrogen in anaestrous females. However, the threshold for pain perception showed a gradually declining trend in both the groups over the next 11 days to reach the control values. This increase in sensitivity to pain or decreased pain threshold could be attributed to the phenomenon of habituation.     

The role of adrenocorticotropic hormone in inhibition of pain reaction in awake rats

The effect of hormones of hypothalamic-pituitary-adrenocortical system on pain sensitivity were studied in experiments on awake Sprague-Dawley males rats. Pain sensitivity was tested by tail flick reaction induced by thermal stimuli. Systemic glucocorticoids and ACTH injection increased the tail flick latency. The ACTH-induced analgesic effect was unaffected by deficiency of glucocorticoids production in pretreatment with pharmacological dose of cortisol but was fully eliminated by pretreatment with opiate antagonist naltrexone. These findings suggest that ACTH-induced analgesic effect is mediated by opiate receptors but not by glucocorticoids released in response to ACTH injection.     

Locating the beginnings of pain

This paper examines the question of whether a fetus can feel pain. The question is divided into four sub questions: What is pain? What is the neurology of pain processing? What is the fetus? Are there good reasons for holding that fetuses feel pain? Pain is suggested to be a multi-dimensional phenomenon drawing on emotional and sensory processes – a consequence of a gradual development involving a number of noxious events rather than an automatic consequence of injury or disease. The non-automaticity of pain is emphasised in the discussion of pain neurology that defies explanations based on a specialised neuronal ‘pain-centre’. The development of the fetus is considered with respect to developmental neurobiology, behavioural and neurological responses to stimulation, and hormonal and neurochemical responses to noxious stimulation. While acknowledging that the development of the fetus is complex, especially after 26 weeks gestation, considerable development is still to occur, even after birth. The fetal pain literature is criticised for tending to exaggerate fetal development. Finally, the difficulty of explaining the subjectivity of pain in materialist terms is discussed. Pain is suggested to arise with development of the necessary neurological, cognitive and emotional structures. Pain experience is placed at approximately 12 months of age, though this is within the context of a continuum of awareness rather than a straight ‘on-off’ switch. The major moral implication of this stance is to place the burden of proof for analgesic use onto clinical measures, rather than relying upon the, so far, poorly supported assumption of pain awareness.     

The influence of women’s attachment style on the chronobiology of labour pain,analgesic consumption and pharmacological effect

Circadian variation in biological rhythms has been identified as affecting both labour pain and the pharmacological properties of analgesics. In the context of pain, there is also a growing body of evidence suggesting the importance of adult attachment. The purpose of this study was to examine whether labour pain, analgesic consumption and pharmacological effect are significantly affected by the time of day and to analyse whether this circadian variation is influenced by women’s attachment style. This prospective observational study included a sample of 81 pregnant women receiving patient-controlled epidural analgesia (PCEA). Attachment was assessed with the Adult Attachment Scale – Revised. The perceived intensity of labour pain in the early stage of labour (3?cm of cervical dilatation and before the administration of PCEA) was measured using a visual analogue scale (VAS). Pain was also indirectly assessed by measuring the consumption of anaesthetics. The latency period and the duration of effect were recorded for a chronopharmacology characterisation. Pain, as assessed with the VAS, was significantly higher in the night-time group than in the daytime group. An insecure attachment style was significantly associated with greater labour pain at 3?cm of cervical dilatation (p?<?0.001) and before the beginning of analgesia (p?<?0.001) as well as with higher analgesic consumption and lower pharmacological efficacy (p?<?0.05). The time of day was significantly associated with the pharmacological effect: the latency period was longer at night, and the duration of the pharmacological effect was longer during the daytime. The interaction between time of day and attachment style was not significant for any of the study variables. Our results provide evidence of the importance of circadian variation in studying labour pain and the pharmacological effect of labour analgesia involving epidural blockage with a PCEA regimen. Moreover, although there was no evidence that attachment style influenced the circadian variation, these data emphasise that insecure attachment patterns are a risk factor for greater labour pain and analgesic consumption, which should be considered in pain management approaches.