Robert W. Hurley

The Analgesic Effects of Perioperative Gabapentin on Postoperative Pain: A Meta-Analysis

Background and Objectives: Gabapentin is an anticonvulsant that has been shown to be effective in the treatment of neuropathic and inflammatory pain in animal and human studies. The analgesic effect of its perioperative use has not been fully elucidated. Methods: This systematic review (meta-analysis) included 12 randomized controlled trials of 896 patients undergoing a variety of surgical procedures that investigated the impact of perioperative administration of gabapentin on postoperative outcome. Results: The pooled visual analog scores for pain at 4 hours and 24 hours were significantly less in those patients who received gabapentin (weighted mean difference [WMD] = −1.57; 95% confidence interval [CI], −2.14 to −0.99 and WMD = −0.74; CI, −1.03 to −0.45, respectively). A concomitant decrease in opioid usage by those patients who received gabapentin was also noted (odds ratio [OR] = −17.84; CI, −23.50 to −12.18). Gabapentin administration was associated with sedation and anxiolysis (OR = 3.28; CI, 1.21-8.87) but not associated with a difference in lightheadedness, dizziness, nausea, or vomiting. Conclusions: Based on this systematic review, perioperative oral gabapentin is a useful adjunct for the management of postoperative pain that provides analgesia through a different mechanism than opioids and other analgesic agents and would make a reasonable addition to a multimodal analgesic treatment plan.

Randomized Placebo-Controlled Study Evaluating Lateral Branch Radiofrequency Denervation for Sacroiliac Joint Pain

Background:Sacroiliac joint pain is a challenging condition accounting for approximately 20% of cases of chronic low back pain. Currently, there are no effective long-term treatment options for sacroiliac joint pain. Methods:A randomized placebo-controlled study was conducted in 28 patients with injection-diagnosed sacroiliac joint pain. Fourteen patients received L4–L5 primary dorsal rami and S1–S3 lateral branch radiofrequency denervation using cooling-probe technology after a local anesthetic block, and 14 patients received the local anesthetic block followed by placebo denervation. Patients who did not respond to placebo injections crossed over and were treated with radiofrequency denervation using conventional technology. Results:One, 3, and 6 months after the procedure, 11 (79%), 9 (64%), and 8 (57%) radiofrequency-treated patients experienced pain relief of 50% or greater and significant functional improvement. In contrast, only 2 patients (14%) in the placebo group experienced significant improvement at their 1-month follow-up, and none experienced benefit 3 months after the procedure. In the crossover group (n = 11), 7 (64%), 6 (55%), and 4 (36%) experienced improvement 1, 3, and 6 months after the procedure. One year after treatment, only 2 patients (14%) in the treatment group continued to demonstrate persistent pain relief. Conclusions:These results provide preliminary evidence that L4 and L5 primary dorsal rami and S1–S3 lateral branch radiofrequency denervation may provide intermediate-term pain relief and functional benefit in selected patients with suspected sacroiliac joint pain. Larger studies are needed to confirm these results and to determine the optimal candidates and treatment parameters for this poorly understood disorder.

Gabapentin and Pregabalin Can Interact Synergistically with Naproxen to Produce Antihyperalgesia

Background Gabapentin and pregabalin are anticonvulsants with antihyperalgesic effects in animal models of neuropathic and inflammatory nociception. This study characterized the manner in which gabapentin or pregabalin interacts with naproxen to suppress thermal hyperalgesia and inflammation in the carrageenan model of peripheral inflammation. Methods Gabapentin, pregabalin, naproxen, or a fixed-dose ratio of gabapentin + naproxen or pregabalin + naproxen was administered orally to rats after the induction of inflammation by intraplantar injection of &lgr;-carrageenan in one hind paw. Nociceptive thresholds were determined by the radiant heat paw-withdrawal test. Paw edema was measured by plethysmometry. Drug plasma concentrations were determined by a liquid chromatography–mass spectroscopy–mass spectroscopy method. Results Gabapentin, pregabalin, and naproxen alone reversed thermal hyperalgesia with ED50 values of 19.2, 6.0, and 0.5 mg/kg, respectively. Mixtures of gabapentin + naproxen in fixed-dose ratios of 50:1, 10:1, or 1:1 interacted synergistically to reverse carrageenan-induced thermal hyperalgesia. However, 1:50 gabapentin + naproxen produced only additive effects. No combination of gabapentin + naproxen decreased paw edema in a manner greater than additive. Plasma concentrations of gabapentin and naproxen were unaltered by the addition of the other drug. The mixture of 10:1 of pregabalin + naproxen interacted synergistically to reverse thermal hyperalgesia on the inflamed hind paw, whereas mixtures of 1:1 or 1:10 produced additive effects. Conclusions These data suggest that gabapentin + naproxen and pregabalin + naproxen can interact synergistically or additively to reverse thermal hyperalgesia associated with peripheral inflammation. Therefore, the use of gabapentin or pregabalin in low-dose combinations with naproxen may afford therapeutic advantages for clinical treatment of persistent inflammatory pain.

Effect of postoperative epidural analgesia on morbidity and mortality following surgery in medicare patients.

Background Because of the uncertainty and limitations in available randomized controlled trials, we performed an analysis of the Medicare claims database to determine whether an association exists between postoperative epidural analgesia and mortality. Methods A 5% nationally random sample of Medicare beneficiaries from 1997 to 2001 was analyzed to identify patients undergoing segmental excision of the lung (International Statistical Classification of Diseases, Ninth Revision, Clinical Modification codes 32.3 and 32.4), complete pneumonectomy (code 32.5), partial excision of large intestine (codes 45.73 and 45.76), anastomosis of the esophagus (codes 42.5 and 42.6), total knee replacement/revision (codes 81.54 and 81.55), total/radical abdominal hysterectomy (codes 68.4 and 68.6), partial/radical pancreaticoduodenectomy (codes 52.5 and 52.7), partial/complete nephrectomy (codes 55.4 and 55.5), partial/complete cystectomy (codes 57.6 and 57.7), hepatotomy/lobectomy of the liver (codes 50.0 and 50.3), partial/total gastrectomy (codes 43.5 to 43.9), and radical retropubic prostatectomy (codes 60.4 and 60.5). Patients were divided into 2 groups, depending on the presence or absence of postoperative epidural analgesia. The rate of major morbidity and death at 7 and 30 days after surgery were compared. Multivariate regression analyses incorporating race, gender, age, comorbidities, hospital size, hospital teaching status, and hospital technology status were performed. Results The presence of epidural analgesia was associated with a significantly lower odds of death at 7 days (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.38 to 0.73; P = .0001) and 30 days (OR, 0.74; 95% CI, 0.63 to 0.89; P = .0005) after surgery; however, no difference was seen between the groups with regard to overall major morbidity, with the exception of an increase in pneumonia at 30 days for the epidural group (OR, 1.91;[95% CI, 1.09 to 3.34; P = .02). Conclusions Postoperative epidural analgesia may contribute to lower odds of death after surgery.

Clinical predictors of success and failure for lumbar facet radiofrequency denervation.

ObjectiveTo determine the clinical factors associated with the success and failure of radiofrequency denervation of the lumbar facet joints. MethodsClinical data were garnered from 3 academic medical centers on 192 patients with low back pain who underwent radiofrequency denervation after a positive response to diagnostic blocks. Success was defined as ≥50% pain relief lasting at least 6 months. Factors evaluated for their association with outcome included duration of pain, opioid use, symptom location, paraspinal tenderness, pain exacerbated by extension/rotation (ie, facet loading), MRI abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery and levels treated. ResultsThe only factor associated with a successful outcome was paraspinal tenderness. Variables that correlated with treatment failure were ‘facet loading,’ long duration of pain, and previous back surgery. ConclusionsIt is counterproductive to use ‘facet loading’ as the sole basis for choosing patients for facet interventions. In patients at high risk for treatment failure, taking additional steps to reduce the rate of false-positive screening blocks may improve outcomes.

Obesity and Weight Loss in the Treatment and Prevention of Osteoarthritis

Obesity is associated with an increasing prevalence of musculoskeletal complaints and pain. Obesity is a major risk factor for osteoarthritis (OA), and pain can manifest in load‐bearing and nonload‐bearing joints. The lumbar spine and the knee are 2 primary sites for pain onset in the obese patient. Irrespective of the weight loss method, reduction of body fat can lower the mechanical and inflammatory stressors that contribute to OA. Single or combined methods of weight loss including exercise, dietary modification, medications, and bariatric surgery are associated with lower joint pain and increased physical function. Methods of weight loss or maintenance in early years may reduce the life exposure of joints to the obesity induced stressors on load bearing joints.

A double-blind, placebo-controlled, dose-response pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy.

Background:In recent years, convincing evidence has emerged implicating tumor necrosis factor α as a causative factor in radiculopathy and discogenic back pain. But although preliminary open-label studies demonstrated promising results for the treatment of low back pain with tumor necrosis factor-α inhibitors, early optimism has been tainted by a controlled study showing no significant benefit in sciatica. To determine whether outcomes might be improved by a more direct route of administration, the authors evaluated escalating doses of intradiscal etanercept in 36 patients with chronic lumbosacral radiculopathy or discogenic low back pain. Methods:A double-blind, placebo-controlled pilot study was conducted whereby six patients received 0.1, 0.25, 0.5, 0.75, 1.0, or 1.5 mg etanercept intradiscally in each pain-generating disc. In each escalating dose group of six patients, one received placebo. A neurologic examination and postprocedure leukocyte counts were performed in all patients at 1-month follow-up visits. In patients who experienced significant improvement in pain scores and function, follow-up visits were conducted 3 and 6 months after the procedure. Results:At 1-month follow-up, no differences were found for pain scores or disability scores between or within groups for any dose range or subgroup of patients. Only eight patients remained in the study after 1 month and elected to forego further treatment. No complications were reported, and no differences were noted between preprocedure and postprocedure leukocyte counts. Conclusions:Although no serious side effects were observed in this small study, a single low dose of intradiscal etanercept does not seem to be an effective treatment for chronic radicular or discogenic low back pain.

Factors predicting success and failure for cervical facet radiofrequency denervation: a multi-center analysis.

Background and Objectives: The concept of radiofrequency denervation has recently come under question in light of several studies showing minimal to no benefit. One possibility proposed for these negative outcomes is poor selection criteria. Unlike virtually all other spine interventions, the factors associated with success and failure for cervical facet denervation have yet to be determined. The purpose of this study is to determine which demographic, clinical and treatment factors are associated with cervical facet radiofrequency denervation outcomes. Methods: Data were garnered from 3 academic medical centers on 92 patients with chronic neck pain who underwent radiofrequency denervation after a positive response to diagnostic local anesthetic blocks. Success was defined as at least 50% pain relief lasting at least 6 months. Variables evaluated for their association with outcome included age, sex, duration of pain, opioid use, pain referral pattern, paraspinal tenderness, pain exacerbated by extension/rotation, magnetic resonance image abnormalities, diabetes, smoking, scoliosis, obesity, prior surgery, and levels treated. Results: The only clinical variable associated with success was paraspinal tenderness. Factors associated with treatment failure included radiation to the head, opioid use, and pain exacerbated by neck extension and/or rotation. Conclusions: Selecting patients based on key clinical variables may increase the chance of treatment success for cervical facet radiofrequency denervation.

The ability of diagnostic spinal injections to predict surgical outcomes

BACKGROUND:Since their first description more than 80 yr ago, the use of diagnostic spinal injections to predict surgical outcomes has been the subject of intense controversy. Because there are no standardized guidelines or substantive reviews on this topic, their use has remained inconsistent. METHODS:Diagnostic procedures included in this review were lumbar and cervical discography, lumbar facet blocks, lumbar and cervical selective nerve root blocks, and sacroiliac (SI) joint injections. We garnered materials via MEDLINE and OVID search engines, books and book chapters, bibliographic references, and conference proceedings. RESULTS:The lack of randomized, comparative studies for all blocks limited the conclusions that could be drawn. For the data that do exist, there is limited evidence that lumbar discography improves fusion outcomes, and no evidence that it influences disk replacement results. Although limited in scope, the current literature supports the notion that cervical discography improves surgical outcomes. There is strong evidence that lumbar selective nerve root blocks improve the identification of a symptomatic nerve root(s), and moderate evidence that both lumbar and cervical nerve root blocks improve surgical outcomes. The data supporting surgery for facet arthropathy are weak, and the use of screening blocks does not appear to improve outcomes. The data supporting SI joint fusion for degenerative, nontraumatic injuries are similarly weak. Because the most reliable method to diagnose a painful SI joint is with low volume, diagnostic injections, one might reasonably conclude that screening blocks improve surgical outcomes. However, this conclusion is not supported by indirect evidence. CONCLUSIONS:The ability to evaluate the effect of diagnostic blocks on surgical outcomes is limited by a lack of randomized studies, methodological flaws, and wide-ranging discrepancies with regard to injection variables, surgical technique, and outcome measures. More research is needed to optimize injection techniques and determine which, if any, diagnostic screening blocks can improve surgical outcomes.

A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist

&NA; This study used concordant behavioral and electrophysiological approaches to examine the actions of the prototypic kappa opioid receptor agonist U69593 in the rostral ventromedial medulla (RVM). In vitro whole‐cell voltage clamp recordings indicated that bath application of U69593 produced outward currents in primary cells in the RVM. In secondary cells, which comprised 80% of the population, U69593 produced a concentration‐dependent and norbinaltorphimine (norBNI)‐reversible inhibition of evoked excitatory postsynaptic currents (EPSCs) in the absence of any postsynaptic effect. U69593 also decreased the frequency, but not the amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in secondary cells. The inhibition of excitatory inputs to secondary cells would be consonant with disinhibition of primary cells and the production of antinociception. Consistent with this expectation, the activation of kappa opioid receptors in the RVM by microinjection of U69593 produced a dose‐dependent increase in paw‐withdrawal latency that was antagonized by norBNI. Furthermore, microinjection of norBNI in the RVM antagonized the increases in paw‐withdrawal latency and hot‐plate latency produced by systemically‐administered U69593. In contrast, microinjection of norBNI in the RVM did not antagonize the increase in tail‐flick latency produced by systemically‐administered U69593. Also, microinjection of U69593 in the RVM did not increase tail‐flick latency. The highly test‐dependent nature of U69593’s effects suggests that the mechanisms by which neurons in the RVM modulate thermal nociceptive responses evoked from the tail and hindpaw are not uniform. Collectively, these data suggest that the RVM is a primary site of action for the antinociceptive actions of kappa opioid receptor agonists and that the mechanism most likely involves a presynaptic inhibition of excitatory inputs to secondary cells. Thus, disinhibition of pain inhibitory neurons in the RVM is likely to be a common mechanism by which opioid receptor agonists produce antinociception, whether by the direct inhibition of inhibitory secondary cells, as in the case of mu opioid receptor agonists, or by a reduction in the excitatory drive to these neurons, as in the case of kappa opioid receptor agonists.