Intrathecal Morphine Use in Adolescent Idiopathic Scoliosis Surgery is Associated with Decreased Opioid Use and Decreased Length of Stay

BackgroundLength of stay (LOS) in the hospital following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) has decreased over the past decade due to well-defined postoperative clinical pathways, earlier mobilization, and improved pain control methods. Historically, liberal use of parenteral and oral opioids for pain control caused side effects, resulting in delayed discharge. Intraoperative intrathecal morphine (ITM) has been posited to reduce the need for postoperative opioids and to expedite the discharge process. This study examines the relationship between the use of ITM with average required postoperative opioid usage and with average LOS.MethodsThis IRB-approved retrospective cohort study examined 105 patients with AIS who received PSF with instrumentation split into two cohorts. One cohort underwent PSF via standard surgical protocol (n=40) while the other cohort received intraoperative ITM with the standard surgical protocol (n=65). Power analysis demonstrated a study power of 0.8. LOS and total postoperative opioid analgesic medication (morphine milligram equivalent, MME) data were collected. Age at surgery, gender, number of spinal levels fused, estimated intraoperative blood loss (EBL), preoperative Cobb angle, and any complications related to the use of ITM were also recorded. Continuous variables were analyzed with Student’s t-test and categorical variables were analyzed with chi-square independent-sample tests using SAS 9.4 (α = 0.05).ResultsPatients who were treated with ITM displayed shorter LOS (p<0.0001) and reduced postoperative analgesic requirement (p<0.0001). Patients who received ITM spent an average of 1.8 fewer midnights in the hospital and received an average of 221.2 MME less than patients who received standard protocol (57% decrease). There were no significant differences between the two groups for any other variable.ConclusionIntraoperative ITM is a simple and effective treatment for scoliosis surgeons to better control postoperative pain in patients, reduce the risk of dependency, and achieve earlier discharge from the hospital. Shortened LOS reduces the overall cost of care, benefitting patients, hospitals, and insurance companies. Based on the results of this study and several earlier studies, the authors recommended that scoliosis surgeons consider incorporating use of ITM into their standard operative protocols. Level of Evidence: IV     

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.     

Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat's intervertebral disc after experimentally induced scoliotic deformity

Minimally invasive spine surgery is becoming more common in the treatment of adult lumbar degenerative disorders. Minimally invasive techniques have been utilized for multilevel pathology, including adult lumbar degenerative scoliosis. The next logical step is to apply minimally invasive surgical techniques to the treatment of adolescent idiopathic scoliosis (AIS). However, there are significant technical challenges of performing minimally invasive surgery on this patient population. For more than two years, we have been utilizing minimally invasive spine surgery techniques in patients with adolescent idiopathic scoliosis. We have developed the present technique to allow for utilization of all standard reduction maneuvers through three small midline skin incisions. Our technique allows easy passage of contoured rods, placement of pedicle screws without image guidance, and allows adequate facet osteotomy to enable fusion. There are multiple potential advantages of this technique, including: less blood loss, shorter hospital stay, earlier mobilization, and relatively less pain and need for pain medication. The operative time needed to complete this surgery is longer. We feel that a minimally invasive approach, although technically challenging, is a feasible option in patients with adolescent idiopathic scoliosis. Although there are multiple perceived benefits, long term data is needed before it can be recommended for routine use.     

A retrospective analysis of health-related quality of life in adolescent idiopathic scoliosis children treated by anterior instrumentation and fusion

Background

Idiopathic scoliosis is the most common type of spinal deformity. Scoliosis is defined as a lateral curvature of the spine greater than 10° accompanied by rotation of the vertebrae. The treatment available for adolescent idiopathic scoliosis is observation, orthosis, and surgery. The surgical options include open anterior release and instrumentation, posterior instrumentation, and thoracoscopic approaches. The Scoliosis Research Society Questionnaire (SRS-30) is a specific instrument to measure health-related quality of life in patients with scoliosis, who had or had not undergone surgery. The purpose was to assess the post-operative functional outcome using SRS-30 in children who underwent anterior release, instrumentation, and fusion using autogenous rib graft for adolescent idiopathic scoliosis (AIS).

Methods

In a retrospective cohort study, 25 patients between the ages of 11 and 17 years, who underwent anterior release, instrumentation, and fusion using autogenous rib graft for adolescent idiopathic scoliosis (AIS) between 2008 and 2014, were included in the study.

Results

The total average score was 4.26 with a SD of 0.014 and had maximum average score 4.5 (for pain) and minimum average score 3.8 (for self-image).

Conclusion

Anterior release, instrumentation, and fusion using autogenous rib graft is having good functional outcome in all domains.

     

Induction of pain facilitation by sustained opioid exposure: relationship to opioid antinociceptive tolerance

Opioid analgesics are frequently used for the long-term management of chronic pain states, including cancer pain. The prolonged use of opioids is associated with a requirement for increasing doses to manage pain at a consistent level, reflecting the phenomenon of analgesic tolerance. It is now becoming clearer that patients receiving long-term opioid therapy can develop unexpected abnormal pain. Such paradoxical opioid-induced pain, as well as tolerance to the antinociceptive actions of opioids, has been reliably measured in animals during the period of continuous opioid delivery. Several recent studies have demonstrated that such pain may be secondary to neuroplastic changes that result, in part, from an activation of descending pain facilitation mechanisms arising from the rostral ventromedial medulla (RVM). One mechanism which may mediate such pain facilitation is through the increased activity of CCK in the RVM. Secondary consequences from descending facilitation may be produced. For example, opioid-induced upregulation of spinal dynorphin levels seem to depend on intact descending pathways from the RVM reflecting spinal neuroplasticity secondary to changes at supraspinal levels. Increased expression of spinal dynorphin reflects a trophic action of sustained opioid exposure which promotes an increased pain state. Spinal dynorphin may promote pain, in part, by enhancing the evoked release of excitatory transmitters from primary afferents. In this regard, opioids also produce trophic actions by increasing CGRP expression in the dorsal root ganglia. Increased pain elicited by opioids is a critical factor in the behavioral manifestation of opioid tolerance as manipulations which block abnormal pain also block antinociceptive tolerance. Manipulations that have blocked enhanced pain and antinociceptive tolerance include reversible and permanent ablation of descending facilitation from the RVM. Thus, opioids elicit systems-level adaptations resulting in pain due to descending facilitation, upregulation of spinal dynorphin and enhanced release of excitatory transmitters from primary afferents. Adaptive changes produced by sustained opioid exposure including trophic effects to enhance pain transmitters suggest the need for careful evaluation of the consequences of long-term opioid administration to patients.     

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.     

Adolescent idiopathic scoliosis: natural history and long term treatment effects

ABSTRACT : Adolescent idiopathic scoliosis is a lifetime, probably systemic condition of unknown cause, resulting in a spinal curve or curves of ten degrees or more in about 2.5% of most populations. However, in only about 0.25% does the curve progress to the point that treatment is warranted.Untreated, adolescent idiopathic scoliosis does not increase mortality rate, even though on rare occasions it can progress to the >100 degrees range and cause premature death. The rate of shortness of breath is not increased, although patients with 50 degrees curves at maturity or 80 degrees curves during adulthood are at increased risk of developing shortness of breath. Compared to non-scoliotic controls, most patients with untreated adolescent idiopathic scoliosis function at or near normal levels. They do have increased pain prevalence and may or may not have increased pain severity. Self-image is often decreased. Mental health is usually not affected. Social function, including marriage and childbearing may be affected, but only at the threshold of relatively larger curves.Non-operative treatment consists of bracing for curves of 25 degrees to 35 degrees or 40 degrees in patients with one to two years or more of growth remaining. Curve progression of >/= 6 degrees is 20 to 40% more likely with observation than with bracing. Operative treatment consists of instrumentation and arthrodesis to realign and stabilize the most affected portion of the spine. Lasting curve improvement of approximately 40% is usually achieved.In the most completely studied series to date, at 20 to 28 years follow-up both braced and operated patients had similar, significant, and clinically meaningful reduced function and increased pain compared to non-scoliotic controls. However, their function and pain scores were much closer to normal than patient groups with other, more serious conditions.Risks associated with treatment include temporary decrease in self-image in braced patients. Operated patients face the usual risks of major surgery, a 6 to 29% chance of requiring re-operation, and the remote possibility of developing a pain management problem.Knowledge of adolescent idiopathic scoliosis natural history and long-term treatment effects is and will always remain somewhat incomplete. However, enough is know to provide patients and parents the information needed to make informed decisions about management options.     

Spinal plasticity of acute opioid tolerance

Spinal acute opioid tolerance remains mechanistically undercharacterized. Expanded clinical use of direct spinal administration of opioids and other analgesics indicates that studies to further understand spinal mechanisms of analgesic tolerance are warranted. Rodent models of spinal administration facilitate this objective. Specifically, acute spinal opioid tolerance in mice presents a plasticity-dependent, rapid, and efficient opportunity for evaluation of novel clinical agents. Similarities between the pharmacology of acute and chronic spinal opioid tolerance, neuropathic pain, and learning and memory suggest that this model may serve as a high through-put predictor of bioactivity of novel plasticity-modifying compounds.     

"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.     

Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure

The opioid analgesics, commonly exemplified by morphine, represent the best option for the treatment of severe pain and for the management of chronic pain states, of both malignant and nonmalignant origin. It is well recognized that the prolonged use of opioids is associated with a requirement for ever-increasing doses in order to maintain pain relief at an acceptable and consistent level. This phenomenon is termed analgesic tolerance. While the concept that tolerance can develop as a result of cellular adaptations to the presence of the opioid has been proposed, it is now becoming abundantly clear that tolerance may also be related to a state of hyperalgesia that results from exposure to the opioid itself. Patients who receive long-term opioid therapy sometimes develop unexpected, abnormal pain. Similar paradoxical opioid-induced pain has been confirmed in a number of animal studies, even during the period of continuous opioid delivery. A number of recent studies have demonstrated that such pain may be secondary to neuroplastic changes that occur in the brain and spinal cord. One such change may be the activation of descending pain facilitation mechanisms arising from the rostral ventromedial medulla (RVM) elicited in part by increased activity of cholecystokinin (CCK) in the RVM. A cascade of pronociceptive events may follow, such as opioid-induced upregulation of spinal dynorphin levels that promotes enhanced input from primary afferent nociceptors. This mechanism appears to depend on intact descending pathways from the RVM, since interrupting this pathway abolishes enhanced abnormal pain. Furthermore, extended opioid exposure also can elicit increased calcitonin gene related peptide (CGRP) and substance P expression in the dorsal root ganglia. It is probable that increased pain elicited by opioids is a critical factor in the behavioral manifestation of opioid tolerance because the same manipulations that block abnormal pain also block antinociceptive tolerance. Taken together, such studies show that opioids elicit systems-level adaptations resulting in pain due to descending facilitation, upregulation of spinal dynorphin, and enhanced, evoked release of excitatory transmitters from primary afferents. These adaptive changes in response to sustained exposure to opioids indicate the need for the evaluation of the clinical consequences of long-term opioid administration. Additionally, these findings suggest a need for novel chemistry involving design of agents that may counteract opiate-induced neuroplastic adaptations resulting in pain relief without analgesic tolerance.     

Synergistic interactions between cannabinoid and opioid analgesics

Cannabinoids and opioids both produce analgesia through a G-protein-coupled mechanism that blocks the release of pain-propagating neurotransmitters in the brain and spinal cord. However, high doses of these drugs, which may be required to treat chronic, severe pain, are accompanied by undesirable side effects. Thus, a search for a better analgesic strategy led to the discovery that delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, enhances the potency of opioids such as morphine in animal models. In addition, studies have determined that the analgesic effect of THC is, at least in part, mediated through delta and kappa opioid receptors, indicating an intimate connection between cannabinoid and opioid signaling pathways in the modulation of pain perception. A host of behavioral and molecular experiments have been performed to elucidate the role of opioid receptors in cannabinoid-induced analgesia, and some of these findings are presented below. The aim of such studies is to develop a novel analgesic regimen using low dose combinations of cannabinoids and opioids to effectively treat acute and chronic pain, especially pain that may be resistant to opioids alone.     

患者静脉自控镇痛与患者硬膜外自控镇痛的比较

术后自控镇痛方法有：患者静脉自控镇痛（Patient-controlled Intravenous Analgesia, PCIA）、患者硬膜外自控镇痛 (Patient-controlled Epidural Analgesia, PCEA）、患者区域自控镇痛（Patient-controlled Regional Analgesia, PCRA)、患者皮下自控镇痛 (Patient-controlled Subcutaneous Analgesia, PCSA)、患者自控鼻内镇痛（Patient-controlled intranasal analgesia, PCINA)、芬太尼HCI 电离子渗入疗法经皮系统（Fentanyl Iontophoretic Transdermal System, ITS)和连续椎旁阻滞（Continuous Paravertebral block, CPVB） 等。目前在临床工作中较常使用的主要是PCIA 和PCEA。有研究报道,与PCIA 比较,PCEA 镇痛效果更确切,恶心、呕吐及嗜睡发 生率低;但也有报道认为,与PCEA 相比,PCIA 实施相对方便,同时也可以提供令患者满意的镇痛效果,适用范围更广。目前对于 这两种镇痛方法的效果优劣尚无确切的定论,在此就PCIA 和PCEA的镇痛药物特点、镇痛效果、副反应及对免疫功能和肿瘤患 者远期生存率的影响作一综述。     

LenkeⅡ型青少年特发性脊柱侧凸患者内固定冠状面失衡的相关因素分析

目的:探讨Lenke II型青少年特发性脊柱侧凸患者内固定冠状面失衡相关因素分析。方法:选取我院骨科已确诊为Lenke II青少年特发性脊柱侧凸患者60例,根据术前脊柱柔韧度、risser分级水平、支具支持治疗、椎体融合数、内固定系统选择等多方面影响因素对内固定后冠状面失平衡情况发生率进行分析评估,其数据结果应用统计学软件SPSS 17.0处理。结果:对术后患者评估比较,多种因素均可影响内固定后冠状面失平衡情况发生,表现为:脊柱柔韧度低、risser分级高、长时间支具佩戴、延长融合椎体范围、先进钉棒系统方案选择均可明显提高术后疗效,降低内固定后冠状面失平衡情况发生率(P0.05),其结果均有统计学意义。结论:临床上通过对患者脊柱柔韧度、risser分级情况评估来判断脊柱成熟度,并在术后积极支具辅助治疗,选用钉棒固定系统并延长融合椎体节段,可明显降低内固定后冠状面失平衡情况发生,提高远期随访疗效。     

超前镇痛对VATS肺叶切除患者阿片类药物使用的影响

目的:探讨术前应用对乙酰氨基酚和加巴喷丁对电视辅助胸腔镜肺叶切除患者术后阿片类药物使用、恶心呕吐的影响。方法:收集2016年1月至2018年12月因非小细胞肺癌就诊于我科行电视辅助胸腔镜肺叶切除的患者,收集患者临床资料包括年龄、性别、BMI、合并症、美国麻醉医师协会麻醉分级、肿瘤分级、肿瘤部位、手术时间,术中和术后阿片类药物使用情况、术后止吐药使用情况,阿片类药物使用均换算为口服吗啡当量,根据术前是否采用对乙酰氨基酚和加巴喷丁超前镇痛方案将患者分为两组,比较两组患者术前基本情况及术中术后阿片类药物使用情况,分析对乙酰氨基酚和加巴喷丁超前镇痛方案对阿片类药物使用情况的影响。结果:共有241例患者纳入研究,有78例患者术前采用对乙酰氨基酚和加巴喷丁超前镇痛方案,163例患者没有采用该镇痛方案,超前镇痛组患者术中及术后阿片类药物使用剂量、术后24小时呕吐次数、术后止吐药使用剂量均低于没有采用超前镇痛方案的患者,两组患者术后NSAIDs使用和镇静状态没有统计学差异。结论:术前采用对乙酰氨基酚和加巴喷丁超前镇痛方案可减少行电视辅助胸腔镜肺叶切除患者术中及术后阿片类药物使用剂量,降低术后恶心呕吐的发生。     

Comparison in Clinical Outcome of Two Surgical Treatments in Degenerative Scoliosis

To evaluate the clinical outcome of two different surgical treatments in treating degenerative scoliosis. Forty patients with degenerative scoliosis hospitalized in our department from June 2010 to June 2012 were selected. They were randomly divided into two groups. The first group was performed on the points with nerve or spinal compression for decompression, bone grafting, and short-segmental fixation in situ; The second group was treated with sufficient decompression, long-segmental fixation, and short-segmental fusion to operate orthopedic on scoliosis in three dimensions. All patients completed the follow-up period for more than 1 year, with the average of 18 months. Bone grafting fusion was achieved in all of the patients. The second group showed significantly better result in remission rate of postoperative pain and ODI improvement rate than the first group. Long-segmental internal fixation orthopedic is a better surgical option for patients with degenerative scoliosis to achieve sufficient decompression and three-dimensional orthopedic; therefore, it is a better solution for biomechanical reconstruction of spine.     

Morphine and Clonidine Combination Therapy Improves Therapeutic Window in Mice: Synergy in Antinociceptive but Not in Sedative or Cardiovascular Effects

Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α₂-adrenergic receptors (α₂ARs). Analgesics acting at α₂ARs and opioid receptors (ORs) frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α₂AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C). Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic efficacy over either drug alone. These data support the utility of combination adrenergic/opioid therapy in pain management for antinociceptive efficacy with reduced side-effect liability.     

多模式术后镇痛在腹腔镜结肠手术中的应用

目的:理论上联合使用不同机制镇痛药较镇痛药单独使用镇痛效果更完善,在妇科、骨科等手术中已有结论;笔者观察比较腹腔镜结肠手术术使用单一止痛药及联合使用不同机制镇痛药在术后镇痛的效果以及各自不良反应的发生率。方法:择期腹腔镜结肠手术患者90例,随机分为3组,每组30例。A组使用地佐辛+氟比洛酚酯行术后镇痛为多模式镇痛组;B组使用地佐辛行术后镇痛;C组使用氟比洛酚酯行术后镇痛。记录每组术后4、8、12、24 h视觉模糊评分(VAS)及术后不良反应包括嗜睡、躁动、恶心呕吐的发生率。结果:A组术后4 h、8 h的VAS评分低于B、C两组,差异有显著性,A组无嗜睡及躁动发生,发生呕吐1例,不良反应发生率A组低于B、C两组,差异有显著性。结论:地佐辛+氟比洛酚酯联合用药可安全有效应用于腹腔镜结肠手术术后镇痛,是一种有效的多模式术后镇痛方式,在减弱疼痛的放大效应及对中枢神经的作用两方面起效,因而较单独使用地佐辛及氟比洛酚酯有更好的镇痛效果,且不良反应低于单独使用地佐辛及氟比洛酚酯。     

Current methods of controlling post-operative pain.

Until recently, the clinical significance of post-surgical pain and its undertreatment were for the most part unappreciated. Recognition that inadequate analgesia adversely affects the patient's cardiovascular, pulmonary, and emotional status has spurred development of new and highly effective methods of controlling pain. With the introduction of spinal opioid and patient-controlled analgesia (PCA) came the realization that, while such forms of therapy provided superior pain relief, they were not without their own unique and occasionally serious side effects. For this reason, both techniques are more safely provided by highly trained members of a dedicated acute/post-surgical pain service. Although spinal opioid (epidural, intrathecal) techniques are invasive and require patient cooperation, they have a high degree of safety in low-risk populations (ASA 1 and 2). The major therapeutic advantage of spinal opioids is their ability to prevent pain from being perceived. PCA permits patients to titrate intravenous opioids in proportion to their particular level of pain intensity. Although PCA provides effective pain "relief," the technique is incapable of preventing pain from being appreciated. A number of studies have observed that pain scores in patients successfully employing PCA were significantly higher than those noted in individuals treated with epidural opioids. Nevertheless, the control gained by self-administration, uniformity of analgesia, and low level of adverse results associated with PCA provides higher patient satisfaction and decreased sedation when compared with traditional intramuscular dosing. The effectiveness of PCA may be improved by adjusting for patient variables, utilizing opioids having rapid onset, the addition of a basal infusion, and supplementation with non-steroidal anti-inflammatory agents. Interpleural analgesia represents an important therapeutic option in patients sensitive to opioid-induced respiratory depression. The technique is more effective when local anesthetic solutions are continually infused. Analgesic efficacy may be further enhanced by the addition of "low-dose" PCA.     

Effects of intrathecal opioids combined with low-dose naloxone on motilin and its receptor in a rat model of postoperative pain

Aims

To investigate the effects of intrathecal morphine and fentanyl combined with low-dose naloxone on the expression of motilin and its receptor in a rat model of postoperative pain.

Main methods

An intrathecal catheter was implanted, and saline, opioids (morphine and fentanyl) and naloxone were intrathecally administered 7 days later. An incisional pain model was established to induce pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and mechanical allodynia were measured by using a radiant heat and electronic Von Frey filament, respectively. The expression of motilin in the hippocampus, stomach, duodenum, and plasma was determined by ELISA; and the expression of motilin receptor in the hippocampus was detected by Western blot assay.

Key findings

Motilin and its receptor were detected in the hippocampus. Acute incisional pain increased the motilin expression in the hippocampus and duodenum, while decreasing its expression in the gastric body and plasma. Postoperative analgesia with morphine + fentanyl upregulated the expression of motilin in the hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at 1 ng/kg restored motilin to baseline levels. Acute pain, morphine + fentanyl, and naloxone all induced the expression of motilin receptor in the hippocampus.

Significance

Acute pain, postoperative analgesia with opioids, and naloxone significantly impacted the expression of hippocampal and peripheral motilin. Variation trends in all sites were not identical. Intrathecal injection of low-dose naloxone upregulated paw withdrawal thermal latency and enhanced the analgesic effects of opioids. The findings presented here provide a new basis for central and peripheral regulations in GI motility, clinical postoperative analgesia, and management of analgesic complications.     

帕瑞昔布钠在术后镇痛中应用的研究进展

手术方式的不断完善和创新,对术后镇痛提出了更高要求。非甾体抗炎药为我国临床术后镇痛常用的一类药物,近年来应用范围仍在不断扩大,但总结长期术后镇痛用药经验发现,传统的非甾体抗炎药易引起胃肠道毒性反应和血小板抑制,因此迫切需要寻找一种安全、有效的术后镇痛药物。帕瑞昔布钠是一种环氧合酶-2(COX-2)特异性抑制剂,注射使用,可用于术后不同程度疼痛的短期治疗,近年来已被临床实践证实具有良好的疗效和较高的安全性。本文结合已经发表的临床研究报道对该药物在术后镇痛中的应用进展进行综述,旨在对该药物的作用机制、疗效、安全性有一个系统性的认识。