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Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor.

ABSTRACT: The number of patients suffering from postoperative pain due to orthopedic surgery and bone fracture is projected to dramatically increase because the human life span, weight, and involvement in high-activity sports continue to rise worldwide. Joint replacement or bone fracture frequently results in skeletal pain that needs to be adequately controlled for the patient to fully participate in needed physical rehabilitation. Currently, the 2 major therapies used to control skeletal pain are nonsteroidal anti-inflammatory drugs and opiates, both of which have significant unwanted side effects. To assess the efficacy of novel therapies, mouse models of orthopedic and fracture pain were developed and evaluated here. These models, orthopedic surgery pain and bone fracture pain, resulted in skeletal pain-related behaviors that lasted 3 weeks and 8 to 10 weeks, respectively. These skeletal pain behaviors included spontaneous and palpation-induced nocifensive behaviors, dynamic weight bearing, limb use, and voluntary mechanical loading of the injured hind limb. Administration of anti-nerve growth factor before orthopedic surgery or after bone fracture attenuated skeletal pain behaviors by 40% to 70% depending on the end point being assessed. These data suggest that nerve growth factor is involved in driving pain due to orthopedic surgery or bone fracture. These animal models may be useful in developing an understanding of the mechanisms that drive postoperative orthopedic and bone fracture pain and the development of novel therapies to treat these skeletal pains.

SUBMITTER: Majuta LA

PROVIDER: S-EPMC4495732 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor.

Majuta Lisa A LA Longo Geraldine G Fealk Michelle N MN McCaffrey Gwen G Mantyh Patrick W PW

Pain 20150101 1

The number of patients suffering from postoperative pain due to orthopedic surgery and bone fracture is projected to dramatically increase because the human life span, weight, and involvement in high-activity sports continue to rise worldwide. Joint replacement or bone fracture frequently results in skeletal pain that needs to be adequately controlled for the patient to fully participate in needed physical rehabilitation. Currently, the 2 major therapies used to control skeletal pain are nonster ...[more]

PMID: 25599311

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Project description:INTRODUCTION:Ankle fracture surgery is a common procedure, but the influence of anaesthesia choice on postoperative pain and quality of recovery is poorly understood. Some authors suggest a benefit of peripheral nerve block (PNB) in elective procedures, but the different pain profile following acute fracture surgery and the rebound pain on cessation of the PNB both remain unexplored. We present an ongoing randomised study aiming to compare primary PNB anaesthesia with spinal anaesthesia for ankle fracture surgery regarding postoperative pain profiles and quality of recovery. METHODS AND ANALYSIS:AnAnkle Trial is a randomised, dual-centre, open-label, blinded analysis trial of 150 adult patients undergoing primary internal fixation of an ankle fracture. Main exclusion criteria are habitual opioid use, impaired pain sensation, other painful injuries or cognitive impairment. The intervention is ultrasound-guided popliteal sciatic (20?mL) and saphenal nerve (8?mL) PNB with ropivacaine 7.5?mg/mL, and controls receive spinal anaesthesia (2?mL) with hyperbaric bupivacaine 5?mg/mL. Postoperatively all receive paracetamol, ibuprofen and patient-controlled intravenous morphine on demand. Morphine consumption and pain scores are registered in the first 27?hours and reported as an integrated pain score as the primary endpoint. Pain score intervals are 3?hours and we will use the area under curve to get a longitudinal measure of pain. Secondary outcomes include rebound pain on cessation of anaesthesia, opioid side effects (Opioid-Related Symptom Distress Scale), quality of recovery (Danish Quality of Recovery-15 score) and pain scores and medication days 1-7 (diary). ETHICS AND DISSEMINATION:The study has been approved by the Regional Ethics Committees in the Capital Region of Denmark, the Danish Data Protection Agency and the Danish Health and Medical Authority. We will publish the results in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER:AnAnkle Trial is registered in the European Clinical Trials Database (EudraCT 2015-001108-76).

Project description:IntroductionOrthopedic procedures have been associated with increased pain, making perioperative analgesia a major clinical concern. We assessed the efficacy and safety of intravenous parecoxib administration during the perioperative period for postoperative pain relief after orthopedic surgery in adults.MethodsPubMed, Cochrane Library, EMBASE, and clinicaltrial.gov were searched from inception to 23 August 2021 without language restrictions. Randomized controlled trials comparing intravenous parecoxib with placebo or another active treatment for acute postoperative pain in adults after orthopedic surgery were included. The primary outcomes were the pain scores and cumulative morphine consumption. The secondary outcomes included the proportion of patients requiring rescue analgesics and the incidence of adverse events. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered on the International Prospective Register of Systematic Reviews Registration (PROSPERO).ResultsTwenty-seven trials (n = 2840) from more than 20 countries involving six types of orthopedic surgery met the inclusion criteria. Compared with placebo, intravenous parecoxib administration led to reductions in postoperative resting pain scores at 6, 12, 24, and 48 h [mean difference (MD) -0.87, 95% confidence interval [CI] -1.71 to -0.03; MD -0.86, 95% CI -1.26 to -0.46; MD -0.57, 95% CI -0.84 to -0.31; MD -0.40, 95% CI -0.69 to -0.11, respectively], postoperative movement pain scores at 24 and 48 h (MD -0.66, 95% CI -1.14 to -0.19; MD -0.78, 95% CI -1.16 to -0.39, respectively), cumulative morphine consumption (MD -11.30 mg, 95% CI -14.79 to -7.81 mg), and the proportion of patients requiring rescue analgesia (relative risk 0.83, 95% CI 0.77-0.89). There was no difference in the incidence of adverse events between groups.ConclusionLow to moderate evidence indicates that parecoxib might be an effective and safe analgesic in perioperative orthopedic settings. It relieves postoperative orthopedic pain while sparing opioid analgesic consumption without increasing the incidence of adverse events.Prospero registrationCRD42021274939.

Project description:INTRODUCTION:Although more than 30 million patients in the United States undergo ambulatory surgery each year, it remains unclear what percentage of these patients receive a perioperative nerve block. We reviewed data from the 2006 National Survey of Ambulatory Surgery to determine the demographic, socioeconomic, geographic, and clinical factors associated with the likelihood of nerve block placement for ambulatory orthopedic surgery. The primary outcome of interest was the association between primary method of payment and likelihood of nerve block placement. In addition, we examined the association between type of surgical procedures, patient demographics, and hospital characteristics with the likelihood of receiving a nerve block. METHODS:This cross-sectional study reviewed 6000 orthopedic anesthetics from the 2006 National Survey of Ambulatory Surgery data set, which accounted for more than 3.9 million orthopedic anesthetics when weighted. The primary outcome of this study addressed the likelihood of receiving a nerve block for orthopedic ambulatory surgery according to the patient's primary method of payment. Secondary end points included differences in demographics, surgical procedures, adverse effects, complications, recovery profile, anesthesia staffing model, and total perioperative charges in those with and without nerve block. RESULTS:Overall, 14.9% of anesthetics in this sample involved a peripheral nerve block. Length of time in postoperative recovery, total perioperative time, and total charges were less for those receiving nerve blocks. Patients were more likely to receive a nerve block if their procedures were performed in metropolitan service areas (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.19-2.91; P = 0.007) or in freestanding surgical facilities (OR, 2.27; 95% CI, 1.74-2.96; P < 0.0001) and if payment for their surgery was supported by government programs (OR, 2.5; 95% CI, 1.01-6.21; P = 0.048) or private insurance (OR, 2.62; 95% CI, 1.12-6.13; P = 0.03) versus self-pay or charity care. CONCLUSIONS:For patients receiving ambulatory orthopedic surgery in the United States, our results suggest that geographic and socioeconomic factors are associated with different likelihoods of perioperative peripheral nerve block placement.

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Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor.

Publications

Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor.

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