Held at Donald Gordon Centre, Kingston, Ontario, CANADA, March 30, 2012.
"Rationalizing a standard approach to the surgical airway: A review of technique and evidence for efficacy"
“Impact of spontaneous versus evoked neuropathic pain on daily function” (data presentation)
“Surgical vs. classical approach to TAP blocks: A randomized controlled study” (proposal)
“The economics of drug wastage” (update)
, PhD Candidate
, Queen’s Biomedical & Molecular Sciences
"Systemic administration of ultra-low dose alpha 2-adrenoreceptor antagonist atipamezole attenuates morphine tolerance and enhances opioid analgesia in neuropathic pain states"
Judy MAROIS, PGY2
“The Effect of Intraoperative Labetalol on Time to Discharge and Hemodynamic Stability in Laparoscopic Cholecystectomy”(proposal)
“Evaluating Junior Resident Readiness for Independent Anesthesia Call Duties With Simulation” (proposal)
“Do Antidepressants reduce post-operative pain? A systematic review.” (data presentation)
, PhD Candidate, Queen’s Biomedical & Molecular Sciences
"Glial Modulation suppresses modality-specific tactile allodynia in a model of neuropathic pain”
Alex MATTIOLI, PhD Candidate, Queen’s Biomedical & Molecular Sciences
"Ultra-low dose naloxone modulates opioid tolerance independently of Toll-like receptor 4" (poster)
Edmund ONG, PhD Candidate, Queen’s Biomedical & Molecular Sciences
“Delta opioid receptor trafficking is altered following prolonged morphine treatment” (poster)
, Queen’s Biomedical & Molecular Sciences
"Use of Conditioned Place Preference paradigm to measure the negative affect of chronic pain" (poster)
Critical Appraisal Essays
, MD, PGY-1, Queen’s Anesthesiology
“Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy.”
Anesth Analg. 2007 Nov;105(5):1255-62.
Nicole McFadden, MD, PGY-1, Queen’s Anesthesiology
“The perioperative dialogue reduces postoperative stress in children undergoing day surgery as confirmed by salivary cortisol.”
Pediatric Anesthesia 2011; 21:1058-1065.
Vanessa Sweet, MD, PGY1, Queen's Anesthesiology
“Incidence and impact of distracting events during induction of general anaesthesia for urgent surgical cases”
Eur J Anaesth 2010 Aug; 27(8): 683-9
Maggie Thomson, MD, PGY-1, Queen’s Anesthesiology
“Caudal Normal Saline Injections for the Treatment of Post-Dural Puncture Headache.”
Pain Physician 2011; 14:2781-279.
“Comprehensive sonoanatomy module to reduce duration of training and increase accuracy of neuraxial block performance”
Jessie Collings PGY3
Research supervisors: Dr Shyam, Dr Murdoch, Dr McMullen; thanks to Rachel Phelan, Val Wilson
The traditional method for neuraxial regional analgesia relies on palpation of landmarks which may not be accurate or evident, especially in cases of obesity and scoliosis. Even the most experienced anesthesiologists incorrectly estimate the interspace level by palpation 71% of the time (1). Uncertainty of anatomy can result in numerous puncture attempts, trauma to neurovascular structures, and unintentional dural puncture. Ultrasound can increase accuracy in identifying intervertebral levels to 76% compared to 30% with palpation (2). Studies on obstetric patients show that ultrasound also results in better blocks, fewer complications, and increased overall patient satisfaction. Anesthesia trainees had a higher success rate and steeper learning curve with ultrasound-guided epidurals compared to the group that was taught the traditional palpation technique for needle insertion (3). However, ultrasound use in neuraxial regional blocks is still usually reserved for only the most difficult patients.
The overall goal of the current study is to increase the accuracy and reduce the time required to master ultrasound-guided neuraxial blocks in the lumbar region. The project evaluates the efficacy of our educational module at increasing competence and confidence for accurate lumbar ultrasound performance in our anesthesiology residents. The module is designed to describe the role of ultrasound for spine demarcation before placement of a neuraxial block and to familiarize residents with ultrasound technology and techniques. Through use with normal models, residents will become confident with using ultrasound to identify sonoanatomy and optimal needle insertion point before attempting to use it on difficult patients.
Our module encompasses 3 methods of training: 1) verbal instruction
, 2) instructor-guided lumbar ultrasound performance on a model (7 residents,1 hour per week for 4 weeks), and 3) unlimited access to our interactive laptop-based training application. Our outcomes for assessment are: 1) ability to identify the L3 /4 interspace in the paramedian longitudinal view, 2) ability to identify the optimal insertion site in the transverse view, and 3) ability to measure the depth of the dura/ligamentum flavum in the transverse view Prior the completion of the module, the residents fill out a survey addressing their own estimation of competence, potential adoption into practice, most useful/least useful aspects of the course, etc. Some limitations in our study design include a small number of residents and the use of the same models each week, which may lead to memorization of their anatomy by the residents scanning them. We also need to ensure our assessment outcomes are objective and reproducible. We have completed the four week teaching module with our residents and over the next few months, we will be doing data collection, analysis and interpretation. Our goal is to repeat an assessment of knowledge and survey in 3 months time. Results from this pilot can be used to design a multicenter, fully powered investigation to determine the full impact of our comprehensive training module. We can also use this module to teach staff who are unfamiliar with the use of ultrasound for neuraxial techniques.
1. Broadbent CR, Maxwell WB, Ferrie R, Wilson DJ, Gawne-Cain M, Russell, R. Ability of anesthetists to identify a marked lumbar interspace. Anaesthesia 2000; 55: 1122-6.
2. Watson MJ, Evans S, Thorp JM. Could ultrasonography be used by an anaesthetist to identify a specified lumbar interspace before spinal anesthesia? Br J Anaesth 2003; 90: 509-11.
3. Grau T, Bartusseck E, Conradi R, Martin E, Motsch J. Ultrasound imaging improves learning curves in obstetric epidural anesthesia: a preliminary study. Can J Anesth 2003; 50: 1047-50.
A Survey of Health Professional Education in Patient Safety at Queen’s University
Patricia Doyle, David Goldstein, Elizabeth VanDenKerkhof, Dana Edge
Safety is central and critical to quality healthcare. With the current efforts to optimize safe, quality care, more attention has been brought to the integration of patient safety into health education curricula. Much of this effort in Canada is underpinned by the Canadian Patient Safety Institute’s Safety Competencies Framework. The result of the Institute’s study revealed that the integration of patient safety concepts into training has been poor, and launched an initiative which developed a framework composed of six competencies to make patient safety easy to understand and apply at all levels of education. An understanding of current student perspectives on these concepts is necessary in order to integrate these safety concepts and monitor the effectiveness of any changes made. Currently, there is little evidence garnering student perspectives in this domain, particularly amongst medical trainees. The purpose of this study is to understand the quality and content of patient safety education in the medical education at Queen’s University.
Study Design and Methodology:
How do medical trainees describe the patient safety curriculum in the classroom and clinical settings?
Is there a relationship between the patient safety curriculum in the classroom and clinical settings?
Are there differences in students’ perspectives of the patient safety curriculum across stages of training?
This study is a cross-sectional web-based survey. All trainees in the undergraduate (n ~436) and postgraduate (n ~406) medical educational programs were invited to complete the online Modified Health Professional Education in Patient Safety Survey. This is a previously validated questionnaire designed to assess students’ exposure to the six health safety competencies and students’ perceptions on how broader patient safety issues are addressed in their education. Participants were invited via email with two subsequent reminder emails, which directed them to the online questionnaire. A prize incentive was offered for participation. The data collection is occurring from January through March 2012. All data gathered remains confidential. Demographic data will be described using descriptive statistics (mean and standard deviation). For research question #1, frequencies and percentages will be used to summarize findings; for question #2, Spearman rank coefficient will be used, and for question #3, Kruskal-Wallis one-way analysis of variance will be used.
Response rate to date show that 252 medical students (62%) have completed the questionnaire whereas 151 residents (35%) have participated. The questionnaire is available for another 2 weeks, with a targeted response rate of 70%, which was achieved with a previous survey of nursing students. Statistical analysis will follow closure of the questionnaire.
Results from this study will guide future health safety curriculum development for medical education programs at Queen’s University and will serve as a baseline to track trainees’ perspectives about patient safety over time. Plans are also underway to conduct an annual national survey of health professional trainees.
PHARMACOTHERAPY FOR THE PREVENTION OF CHRONIC PAIN AFTER SURGERY
Luis Enrique Chaparro, MD: Department of Anesthesiology & Perioperative Medicine. Queen’s University, Kingston, Canada.
Shane A. Smith, MSc, MD: Department of Anesthesiology & Perioperative Medicine. Queen’s University, Kingston, Canada.
Phil J. Wiffen, BPharm, MSc: UK Cochrane Centre, Oxford, UK
Henry J. McQuay, DM: Nuffield Division of Anaesthetics, Oxford University, Oxford, UK.
R. Andrew Moore, DPhil: Nuffield Division of Anaesthetics,
University of Oxford, Oxford, UK.
Ian Gilron, MD, MSc: Departments of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences. Queen’s University. Kingston, Canada.
Surgery, as a cause of chronic pain, is unique because the injury is planned and predictable . We report here preliminary results of an ongoing systematic review of clinical trials evaluating pharmacotherapy to prevent chronic postsurgical pain in adults.
Our review criteria and search strategy included double-blind, placebo-controlled, randomized adult trials of one or more perioperatively administered drugs that measured pain at least three months after surgery . All reviewed trials are graded using the Cochrane risk of bias tool. The primary outcome was defined as the proportion of participants reporting any pain at, or referred to, the anatomical site of the procedure three months after the procedure. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PaPaS Trials Register were the databases used for the search strategy. Other trials are currently being searched from reference lists of relevant articles in order to complete this review.
The first iteration of the literature search yielded, thus far, 37 trials that met inclusion and evaluated impact on chronic postsurgical pain following administration of: gabapentin or pregabalin (15 trials), NMDA antagonists (14), opioids (2), NSAIDs (2), corticosteroids (2), and single trials of topical local anesthesia
, and allopurinol. Twelve studies followed the patients for 3 months; 17 studies for at least six months; 7 followed the patients for one year and only one for two years.
Results of this ongoing systematic review have revealed evidence that NMDA antagonists and gabapentinoids may play a role in reducing chronic pain after surgery. Imminent completion of the trial search and meta-analysis of combinable studies will serve to quantify the impact of these two drug classes on the development of chronic postsurgical pain.
 Lancet 2006. 367: 1618–25.
 Cochrane Database of Systematic Reviews: Protocols 2010 Issue 1 DOI: 10.1002/14651858.CD008307.
Preoperative beta blocker use associated with cerebral ischemia during carotid endarterectomy
Alexandra Florea, Janet van Vlymen, Samia Ali, Donald Brunet, Joel Parlow
Cerebral ischemia is a known complication of carotid cross-clamping during carotid endarterectomy. While selective intra-luminal shunting has been used for cerebral protection, this procedure may not always be effective and carries its own risks. The purpose of this study was to identify potentially modifiable risk factors for intraoperative cerebral ischemia and shunting during carotid endarterectomy.
We performed a retrospective, case-control chart review of all primary carotid endarterectomies with electroencephalographic (EEG) monitoring and selective shunting performed at our institution between 2000-2010. Operative records were screened for documentation of ischemic EEG changes and shunting at the time of carotid clamping. The remaining charts of patients not requiring shunting were randomized and matched to the shunt cases by year of surgery, and presence or absence of contralateral carotid occlusion. Detailed perioperative data was collected for all shunt and control cases. Results were analyzed using the Mantel-Haenszel test and a multivariable logistic regression model.
The incidence of intraoperative ischemic EEG changes leading to shunt placement gradually decreased by approximately 50% between the first and second 5 year periods of the study, or on average 12% per year (P=0.0032). Chronic beta blocker use was the only preoperative variable that was significantly different between the shunt and control groups, with patients undergoing shunting being more likely to have been receiving beta blockers (33/69 vs 18/69, P=0.01, OR 2.5, 95% CI, 1.2 - 5.1). Intraoperative hemodynamic values were similar for shunt and control groups, as well as for beta blocked and non-beta blocked patients.
The current study found an association between chronic beta blocker use and intraoperative cerebral ischemia in patients undergoing carotid endarterectomy. As this effect did not seem to relate to intraoperative hemodynamics, it is postulated that this observation may involve impaired vasodilation and autoregulation of cerebral blood flow in response to carotid clamping.
Rationalizing a standard approach to the emergency surgical airway: a review of technique and evidence for efficacy
Rebecca M. Gerlach MD1, Kenji Inaba MD2, Regan J. Berg MD2, Demetrios Demetriades MD2
Department of Anesthesiology, Queen’s University, Kingston General Hospital, Kingston, ON
Division of Trauma Surgery and Surgical Critical Care, Los Angeles County Medical Center – University of Southern California, Los Angeles, CA
The patient who cannot be intubated and cannot be ventilated presents an immediate threat to life that, despite multiple advances in the difficulty airway armamentarium, continues to challenge anesthesiologists with the need for an emergent surgical airway. The rarity of this situation
, however, is such that no one provider will attain enough clinical experience to be comfortable with the technique, mandating training with cadaveric or synthetic anatomic models to ensure competency. The ideal surgical airway technique should be simple and reliable, easily replicable, fast, and performable under pressure, yet the optimal approach remains controversial. Both percutaneous and open techniques are described, with a significant trend in the anesthesia literature towards less invasive percutaneous approaches in contrast to the open techniques advocated by surgeons. Attempts to compare the efficacy of various techniques are confounded by significant biases, including use of varying synthetic and cadaveric models and varying provider clinical backgrounds and training. The use of several surgical instruments and multiple approaches has clouded the understanding of open cricothyroidotomy for non-surgeons, while percutaneous techniques mandate a baseline skillset and familiarity with commercial kits, and may not be as reliable in a true clinical situation as airway models suggest.
The current systematic literature review surveys the range of advocated techniques and the evidence for their efficacy, incorporating experience from one of the largest Level 1 trauma centers in the United States, to rationalize an optimal approach for obtaining surgical airway access applicable to surgeons and non-surgeons alike. In addition, multiple outstanding research questions including the impact of distorted neck anatomy on the performance of cricothyroidotomy, the role of stress and previous cricothyroidotomy experience on performance
, and long-term clinical outcomes of emergency cricothyroidotomy are tabulated and the ongoing attempts by our research group to address these issues are described.
Impact of Spontaneous Versus Evoked Neuropathic Pain on Pain-Related Quality of Life
Grant B, Gilron I, Holden R, Orr E.
Background: A substantial percentage (18-42%) of patients with diabetes suffer from disabling pain due to sensory neuropathy. Neuropathic pain is known to have a significant impact on quality of life and activities of daily living. Given that current pain therapies are inadequate for 40-60% of affected patients, much effort is being invested into the identification of new targets of pain modulation. Research into novel drug therapies for pain is largely based upon animal pain models of stimulus-evoked pain since very few animal models of spontaneous pain exist. Patients with neuropathic pain describe an array of sensory abnormalities. These can be pains of a spontaneous nature (those that arise without external stimulation) and evoked pains (abnormal responses to mechanical or thermal stimuli). Spontaneous pain can be continuous, steady and ongoing, or it can be paroxysmal, episodic and intermittent. The relative impact of spontaneous versus evoked pain on quality of life and activities of daily living is unclear. There have been very few reports on the ability of patients to differentiate between these two types of pain and their relative impact on pain-related quality of life. The purpose of this ongoing investigation is to develop a pool of self-report items and descriptors that will describe functionally-relevant differences between spontaneous and stimulus-evoked pain. We expect this research to lead to the development and validation of a pain measurement inventory that could be used to quantify differential impact of analgesic therapies on spontaneous versus evoked chronic pain.
Methods: Following Research Ethics Board approval and informed consent, adult patients with neuropathic pain who experience daily moderate pain for at least 3 months were recruited. In this prospective study, patients completed a pilot version of the “Functional Impact of Neuropathic Evoked and Spontaneous Symptom Evaluation Pain Questionnaire”,a modified Brief Pain Inventory, and the “S-LANSS” neuropathic pain questionnaire.
Results: Preliminary descriptive results of this pilot questionnaire suggest the experience of evoked pain as “often” or more by 57-74% of study subjects and the experience of spontaneous pain as “often” or more by 67-74%. Interestingly, 57% of patients never or only sometimes avoid activities because of evoked pain and 62% say it never or only sometimes interferes with activities. Strikingly, 93% of patients often, very often or always carry on with their regular activities of life despite the pain. The most common factors reported to evoke pain included walking, standing, bedsheets, shoes and socks. The most common situations in which spontaneous pain occurred included watching TV, reading and sitting.
Conclusions: Preliminary results of this pilot questionnaire suggest that subjects with neuropathic pain are able to differentiate between evoked and spontaneous pain both of which appear to be frequent experiences. Given the need to better understand the mechanistic diversity of neuropathic pain and how current and future pain therapies can differentially affect spontaneous versus evoked pain, further development and validation of this type of pain measurement inventory is warranted.
Surgical vs. classical approach to TAP blocks: A randomized controlled study
Erika Nguyen, Tarit Saha, Jasmine Bahrami
TAP blocks have been shown to be superior to intravenous and oral opioids in relieving postoperative pain following various abdominal procedures. The technique was initially described as an anatomical landmark-based approach before the ultrasound guided approach was introduced in 2007 with the expectation of increasing safety and reliability of the TAP block. Recently, a novel technique using an intra-abdominal approach performed by the surgeon has proved to be successful in decreasing postoperative pain following colorectal surgery and cesarean section. It is likely that this approach would be associated with a decreased incidence bowel and organ perforation as it is performed under direct visualization of all abdominal components. On a resources standpoint, a surgical TAP block does not require the involvement of specially trained anesthesiology staff or additional equipment (ultrasound). With a trained surgeon, a TAP block from an intra abdominal approach can be done very quickly, is time efficient and could improve turnover time in OR. Its efficacy over the transcutaneous approach, however, has yet to be proven as no one has compared the two techniques.
Our study aims to demonstrate that the surgical transversus abdominis plane block provides equivalent analgesia to the classical TAP with the added benefits of being a more cost-effective, time-efficient and potentially safer technique.
After obtaining ethics approval, patients scheduled for elective total abdominal hysterectomy +/- bilateral salpingo-oophorectomy using a Pfannenstiel or low midline incision will be randomized into 3 groups. Group A will receive surgical TAP blocks, group B ultrasound-guided transcutaneous TAP blocks and group C will be a control group. A standard postoperative analgesia regimen that includes a PCA-IV will be ordered for all patients. Our primary end points will be pain scores and hemodynamic values (HR, BP) at different times postoperatively. We will include opioid consumption, patient satisfaction, OR time and incidence of side-effects as secondary end points. Patients with a past medical history of chronic pain, fibromyalgia, inflammatory bowel disease or drug allergy to local anesthetics will be excluded from the study.
We plan to conduct a pilot study in order to determine the feasibility and the sample size required for our project. This will also provide our surgeon(s) an opportunity to get familiar and consistent with the surgical TAP block technique.
1. Bharti N, Kumar P, Bala I, Gupta V: The efficacy of a novel approach to transversus abdominis plane block for postoperative analgesia after colorectal surgery. Anesthesia & Analgesia 2011, 112(6):1504-1508.
2. Owen DJ, Harrod I, Ford J, Luckas M, Gudimetla V: The surgical transversus abdominis plane block--a novel approach for performing an established technique. BJOG: An International Journal of Obstetrics & Gynaecology 2011, 118(1):24-27.
The Economics of Anesthesia Drug Wastage
Investigators: Dr. Y. Hayat, Dr. R. Tanzola, Dr. R. Rooney, Dr. Dale Engen
Background: Soaring health care costs have led to an increasing proportion of the federal and provincial budgets being utilized to provide health care services. Both federal and provincial governments have been forcing reductions in health care expenditures. This has lead to hospitals and medical departments, including Anesthesiology, being pressured to bring down their costs and justify expenditures. Anesthetic drugs are a major variable cost for the department and the hospital. Last year total OR anesthetic drug expenditure at KGH was approximately ½ million dollars. More recently we have faced critical shortage of intravenous anesthetic agents that further highlights the need for drug conservation strategies. Gillerman et. al., using a mathematical model, estimated the cost of anesthetic drug wastage to be 26% of an Anesthesiology department’s total drug expenditure. At KGH, this wastage could be approximately $125,000. Weinger calculated drug wastage cost per case of US $ 13.51 and estimated potential aggregate annual savings of US $250-$350 million based on the potential cost savings of $10-$15 per surgical case in the USA. Wagner et. al. used regularly drawn drugs including epinephrine, ephedrine, lidocaine, atropine and succinylcholine in their study and estimated total savings of $ 66,000 per year in a tertiary care hospital. However, none of these studies have directly quantified the amount of total drug wastage. Therefore, the purpose of this study was to directly quantify anesthetic drug wastage.
At least twenty five percent of the Anesthetic drugs are wasted on a given day
To quantify the magnitude of the Anesthetic drugs wastage and to determine the most commonly wasted drugs.
Suggest strategies to improve utilization.
Following institutional ethics approval, we carried out wasted anesthetics drugs collection study for a two week period starting on January 30th. All opened and incompletely used syringes and vials of anesthetic drugs were collected in marked containers. Investigators went through the collection on daily basis to record quantities of the wasted drugs.
The following numbers represent minimum anesthetic drug wastage captured for the two week period, excluding controlled drugs, volatiles, oral and infrequently used anesthetic drugs. This is the minimum due to the fact that drugs from some operating rooms were discarded elsewhere and were missed from the study.
Total projected cost of wasted intravenous anesthetic drugs was $ 45,552
Following drugs were most commonly wasted:
This study quantified the magnitude of Anesthetic drug wastage. Current critical shortage of intravenous anesthetic drugs signifies rational use of these drugs. Following strategies will help optimize drug utilization
Redo study to show impact of conservation strategies on drug wastage post intervention (post critical shortage era)
Have labeled syringes ready to draw drugs such as Atropine and Succinlycholine as oppose to routinely drawing them
Draw smaller quantities and save remaining in the vials for later use such as Rocuronium if full 50 mgs is not needed for a patient
Carry stock of pre-mixed syringes of smaller quantities of Ephedrine and Phenylephrine prepared by OR pharmacy
Consider purchasing secure anesthetic drug cart management system with option for the storage of pre-drawn unused syringes for later use and to ensure patient safety
Our thanks to Ron Koob, Paula King , Joe Raposo & Joanne Bauder Fobert for their help.
SYSTEMIC ADMINISTRATION OF ULTRA-LOW DOSE ALPHA 2-ADRENORECEPTOR ANTAGONIST ATIPAMEZOLE ATTENUATES MORPHINE TOLERANCE AND ENHANCES OPIOID ANALGESIA IN NEUROPATHIC PAIN STATES
Grenier P (1), Milne B (2), Cahill CM (1,2,3). (1) Department of Pharmacology and Toxicology, (2) Department of Anesthesiology, and (3) Centre for Neuroscience Studies, Queen’s University
Two significant obstacles in the therapeutic use of opioid analgesics are the development of tolerance over time and the decreased effectiveness of opioids in the treatment of chronic pain states. Previous studies have investigated the use of spinal administration of ultra-low dose (ULD) a2-adrenergic receptor antagonists to attenuate the development of morphine tolerance. The aim of this study was to confirm the effectiveness of systemic administration of ULD a2-adrenergic antagonist atipamezole in enhancing morphine analgesia in models of opioid tolerance and neuropathic (NP) pain, which has not been previously investigated.
To determine the effects of ULD α2-adrenergic antagonists on the development of opioid tolerance in pain naïve animals, male Sprague-Dawley rats were randomly assigned to groups receiving once daily subcutaneous injections of morphine (5mg/kg), morphine (5mg/kg) plus atipamezole (5ng), atipamezole alone (5ng) or saline vehicle. Thermal tail flick latencies were assessed on day one and day seven over a two hour time course to assess the effect of atipamezole on acute morphine tolerance. Tail flick latencies were also assessed daily, thirty and sixty minutes post-injection for seven days to assess the effect of atipamezole on development of chronic morphine tolerance.
To determine the effect of ULD a-2 adrenergic antagonists on morphine analgesia in a model of NP pain, separate rats were randomly assigned to one of two groups: sham or NP. NP pain was induced through chronic constriction injury (CCI) of the sciatic nerve. Half the animals in each group received once daily subcutaneous injections of low-dose atipamezole (5ng) or saline for eleven days. Thermal and mechanical responses were assessed on days four, seven and ten post-surgery. Once pain hypersensitivity was established, a single injection of morphine (5mg/kg) was administered to all animals, and behaviour was assessed over a two hour time course to determine changes in acute opioid analgesia.
Opioid tolerance developed rapidly over the seven days in morphine-treated animals. In rats co-administered atipamezole, an approximate 30% attenuation of tolerance was observed compared to morphine alone. Neither atipamezole alone nor saline vehicle had any effect on tail flick latencies.
Development of mechanical allodynia was observed in CCI animals over the ten days following surgery, and was significantly attenuated by day ten in those receiving daily low-dose atipamezole compared to saline. No effect on thermal tail flick latencies was observed over the same period.
On day ten, a single acute injection of morphine restored mechanical withdrawal thresholds to pre-surgery baselines in the CCI animals. The duration of the anti-allodynic effects of morphine was significantly prolonged in the animals that had been chronically treated with atipamezole compared to saline. Similarly, following the acute morphine injection, the thermal anti-nociceptive effects were prolonged in the CCI animals treated with atipamezole compared to saline controls.
Chronic systemic administration of ULD a2-adrenergic antagonist atipamezole attenuates the development of morphine tolerance, and enhances and prolongs the anti-allodynic effects of morphine in NP pain states. This may one day prove useful in a clinical setting to enhance the effects of opioid analgesics. Further studies will be performed to determine the mechanism through which adrenergic antagonists modulate opioid receptor activity.