Toward a systematic approach to opioid rotation.

Patients requiring chronic opioid therapy may not respond to or tolerate the first opioid prescribed to them, necessitating rotation to another opioid. They may also require dose increases for a number of reasons, including worsening disease and increased pain. Dose escalation to restore analgesia using the primary opioid may lead to increased adverse events. In these patients, rotation to a different opioid at a lower-than-equivalent dose may be sufficient to maintain adequate tolerability and analgesia. In published trials and case series, opioid rotation is performed either using a predetermined substitute opioid with fixed conversion methods, or in a manner that appears to be no more systematic than trial and error. In clinical practice, opioid rotation must be performed with consideration of individual patient characteristics, comorbidities (eg, concurrent psychiatric, pulmonary, renal, or hepatic illness), and concurrent medications, using flexible dosing protocols that take into account incomplete opioid cross-tolerance. References cited in this review were identified via a search of PubMed covering all English language publications up to May 21, 2013 pertaining to opioid rotation, excluding narrative reviews, letters, and expert opinion. The search yielded a total of 129 articles, 92 of which were judged to provide relevant information and subsequently included in this review. Through a review of this literature and from the authors' empiric experience, this review provides practical information on performing opioid rotation in clinical practice.

Combining opioid and adrenergic mechanisms for chronic pain.

Chronic pain is a highly prevalent medical problem in the United States. Although opioids and serotonin-norepinephrine reuptake inhibitors (SNRIs) have demonstrated efficacy for relief of chronic pain, each has risks of adverse events in patients. Because of the risk of opioid abuse and addiction, combinations reducing opioid requirements are particularly valuable. Opioid and SNRI agents relieve pain by different pathways; concurrent use of each agent separately offers many potential benefits: complementary and possibly synergistic analgesic efficacy, separate titrations of opioid and SNRI effects, and the reduction of opioid requirements. However, few clinical studies have investigated the ideal ratios for combinations of opioids and SNRIs. A number of factors affect whether specific combinations have additive, synergistic, less than additive efficacy, or increase adverse events in patients, including general pharmacokinetic considerations, the potential for pharmacodynamic drug interactions, dose, and timing. Because there is little clinical evidence guiding combination therapy with separate opioid and SNRI agents, using single-molecule agents provides safe and effective therapy and should be the first option presented to patients. The use of empiric combinations of separate opioid and SNRI combinations needs to be considered in light of clinical cautions, including the lack of published evidence to guide dose conversion from any opioid to tramadol or to tapentadol, and vice versa; the need to avoid combinations with known drug interactions; and the need to titrate the dose when adding an SNRI to an opioid, and vice versa.

Timing of neuraxial pain interventions following blood patch for post dural puncture headache.

Post dural puncture headache (PDPH) is a common complication of interventional neuraxial procedures. Larger needle gauge, younger patients, low body mass index, women (especially pregnant women), and "traumatic" needle types are all associated with a higher incidence of PDPH. Currently, an epidural blood patch is the gold-standard treatment for this complication. However, despite the high PDPH cure rate through the use of this therapy, little is known about the physiology behind the success of the epidural blood patch, specifically, the time course of patch formation within the epidural space or how long it takes for the blood patch volume to be resorbed by the body. Of the many unanswered and debated topics related to PDPH and epidural blood patches, one additional specific question that may alter clinical management is when it is safe for patients who have experienced a disruption of the thecal space and have undergone this procedure to have a subsequent epidural or spinal procedure, such as a neuraxial anesthetic (i.e. a spinal anesthetic for an elective outpatient procedure) or an interventional pain procedure for chronic pain management. This question becomes more unclear if the new procedure includes a steroid medication. As an example, an older patient presents with a history of lumbar disc disease and during lumbar epidural steroid injection, an inadvertent wet tap occurs leading to PDPH. Following management with fluids, caffeine, medications, and a successful epidural blood patch, it remains unclear as to when would be the best time frame to consider a second lumbar epidural steroid injection. We identified the 3 main risk factors of subsequent interventional neuraxial procedures as (1) disruption of the epidural blood patch and ongoing reparative processes, (2) epidural procedure failure, and (3) infection. We looked at the literature, and summarized the existing literature in order to enable health care professionals to understand the time course of dural repair as well as the risks of subsequent neuraxial procedures after epidural blood patches. This review poses the question using an evidence based review to discuss the appropriate time course to proceed.

Neuromodulation and palliative medicine.

The palliative care population is generally vulnerable to experiencing medication-induced adverse effects and drug-drug interactions. Neuromodulation may offer particular advantages over systemic medications in this population. Spinal cord stimulation and peripheral nerve stimulation have long been utilized in efforts to provide analgesia for various painful conditions. More recently, deep brain stimulation/motor cortex stimulation has anecdotally been utilized for certain intractable pain states. Although brain electrical stimulation has not been adequately trialed or in some cases even tried at all for management of a variety of symptoms, it is conceivable that in the future it may be a potential therapeutic option in efforts to palliate various severe refractory symptoms (eg, intractable pain, nausea, dyspnea, delirium).

Opioid induced nausea and vomiting.

Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the palliative care population. Unfortunately, among the adverse effects of opioids that may be experienced along with analgesia is nausea, vomiting, and/or retching. Although it is conceivable that in the future, using combination agents (opioids combined with agents which may nullify emetic effects), currently nausea/vomiting remains a significant issue for certain patients. However, there exists potential current strategies that may be useful in efforts to diminish the frequency and/or intensity of opioid-induced nausea/vomiting (OINV).

Cervical radicular pain: the role of interlaminar and transforaminal epidural injections.

Chronic neck pain and cervical radicular pain are relatively common in the adult population. Treatment for chronic radicular pain recalcitrant to conservative management includes surgical management as well as interventional techniques with epidural injections utilizing either an interlaminar approach or transforaminal approach. Although there have been multiple systematic reviews and randomized clinical trials of cervical interlaminar epidural injections, the literature is sparse in reference to cervical transforaminal epidural injections. Overall, there is good evidence for the effectiveness of cervical interlaminar epidural injections in managing cervical disc herniation and fair evidence in managing central spinal stenosis and postsurgery syndrome. The evidence is poor, however, for cervical transforaminal epidural injections. Complications with cervical interlaminar epidural injections are rare, but more commonly occur with transforaminal epidural injections and can be fatal. Emerging concepts in pain include further randomized trials; proper placebo design; focus on control design (either active control or placebo control); and appropriate methodologic quality assessment and evidence synthesis.

Painful boney metastases.

Up to 90% of patients with metastatic or advanced stage cancer will experience significant cancer-related pain. Approximately half or more of patients diagnosed with cancer may experience bone pain. It has been estimated that tumor metastases to the skeleton affects roughly 400,000 US citizens annually. Carcinoma from breast, lung, and prostate cancers account for approximately 80% of secondary metastatic bone disease. Bone metastases may cause devastating clinical complications associated with dramatic reductions in quality of life, mobility, and independence, as well as excruciating refractory pain. Associated complications from osseous metastases also present a substantial economic burden. Currently, there are still a significantly high number of patients suffering with unrelieved pain from osseous metastases. Treatments for painful osseous metastases may not only diminish pain but also may improve quality of life and independence/mobility, and reduce skeletal morbidity, potential pathologic fractures, spinal cord compression, and other "skeletal-related events." Treatment strategies for painful osseous metastases include the following: systemic analgesics, intrathecal analgesics, glucocorticoids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), bisphosphonates, chemotherapeutic agents, inhibitors of RANKL-RANK interaction (eg, denosumab), hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Although the mechanisms underlying the development of bone metastases remain incompletely understood, there appears to be important bi-directional interactions between the tumor and the bone microenvironment. A greater understanding of the pathophysiology of painful osseous metastases may lead to better and more selective targeted analgesic therapy. Additionally, potential future therapeutic approaches to painful osseous metastases may revolutionize approaches to analgesia for this condition, leading to optimal outcomes with maximal pain relief and minimal adverse effects.

Antioxidant therapy for pain relief in patients with chronic pancreatitis: systematic review and meta-analysis.

BACKGROUND: Currently, there is no specific therapy for chronic pancreatitis (CP). The treatment of micronutrient antioxidant therapy for painful CP has been sporadically used for more than 30 years, however, its efficacy are still poorly understood. OBJECTIVE: The purpose of this meta-analysis is to investigate the safety and efficacy of antioxidant therapy for pain relief in patients with CP. SETTING: University Hospital in China STUDY DESIGN: Systematic review and meta-analysis METHODS: Two authors independently reviewed the search results and extracted data and disagreements were resolved by discussion. Effects were summarized using standardized mean differences (SMDs), weighted mean differences, or odds ratio (OR) according to the suitable effect model. MEDLINE, PsycINFO, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials  were searched from 1980 through December 2012. Randomized controlled trials (RCTs) that studied antioxidant supplementation for pain relief in patients with CP were analyzed. RESULTS: Nine randomized controlled trials (RCTs) involving 390 patients were included. Overall, there was no association of antioxidant therapy with pain reduction in CP patients (SMD, -0.55; 95% CI, -1.22 to 0.12; P = 0.67). However, antioxidant therapy significantly increased blood levels of antioxidants in CP patients versus the placebo group (SMD, 1.08; 95% CI, 0.74 to 1.43; P < 0.00001). Interestingly, combined antioxidant (selenium, ß-carotene, vitamin C, vitamin E, methionine) therapy was found to be associated with pain relief (SMD, -0.93; 95% CI, -1.72 to -0.14; P = 0.02), while the trials in which a single antioxidant was used revealed no significant pain relief (SMD, -0.12; 95% CI, -1.23 to 0.99; P = 0.83) in CP patients. Strong evidence was obtained that the antioxidants increased adverse effects (OR, 6.09; 95% CI, 2.29 to 16.17, P < 0.01); nevertheless, none was serious. LIMITATIONS: Because of the small sample, a consolidated conclusion cannot be reached based on current RCTs. Large-sample RCTs are needed to clarify the analgesic effect of antioxidants in CP patients. CONCLUSIONS: Combined antioxidant therapy seems to be a safe and effective therapy for pain relief in CP patients. Measures of total antioxidant status may not help to monitor the efficacy of antioxidant therapy for patients with CP.

Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy.

Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

Buprenorphine in the treatment of non-suicidal self-injury: a case series and discussion of the literature.

A global public health problem, non-suicidal self-injury (NSSI) is highly prevalent in both males and females, and tends to first occur in adolescence. NSSI is correlated with a history of childhood trauma, and with a variety of developmental and psychiatric disorders. NSSI is associated with increased risk of morbidity and premature death from suicide, accidents, and natural causes. Current treatment approaches are inadequate for a substantial number of people. Converging evidence for opioid system dysregulation in individuals with NSSI make this a promising area of investigation for more effective treatments. The pharmacological profile of buprenorphine, a potent µ-opioid partial agonist and κ-opioid antagonist, suggests that it may be beneficial. In this paper, we describe the successful treatment of severe NSSI with buprenorphine in six individuals, followed by discussion and further recommendations.

Painful boney metastases.

Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics.

An update of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. Part I: introduction and general considerations.

In 2011, the Institute of Medicine (IOM) re-engineered its definition of clinical guidelines as follows: "clinical practice guidelines are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." This new definition departs from a 2-decade old definition from a 1990 IOM report that defined guidelines as "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances." The revised definition clearly distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. The IOM committee acknowledged that for many clinical domains, high quality evidence was lacking or even nonexistent. Even though the guidelines are important decision-making tools, along with expert clinical judgment and patient preference, their value and impact remains variable due to numerous factors. Some of the many factors that impede the development of clinical practice guidelines include bias due to a variety of conflicts of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Consequently, a knowledgeable, multidisciplinary panel of experts must develop guidelines based on a systematic review of the existing evidence, as recently recommended by the IOM. Chronic pain is a complex and multifactorial phenomenon associated with significant economic, social, and health outcomes. Interventional pain management is an emerging specialty facing a disproportionate number of challenges compared to established medical specialties, including the inappropriate utilization of ineffective and unsafe techniques. In 2000, the American Society of Interventional Pain Physicians (ASIPP) created treatment guidelines to help practitioners. There have been 5 subsequent updates. These guidelines address the issues of systematic evaluation and ongoing care of chronic or persistent pain, and provide information about the scientific basis of recommended procedures. These guidelines are expected to increase patient compliance; dispel misconceptions among providers and patients, manage patient expectations reasonably; and form the basis of a therapeutic partnership between the patient, the provider, and payers.

An update of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. Part II: guidance and recommendations.

OBJECTIVE: To develop evidence-based clinical practice guidelines for interventional techniques in the diagnosis and treatment of chronic spinal pain. METHODOLOGY: Systematic assessment of the literature. EVIDENCE: I. Lumbar Spine • The evidence for accuracy of diagnostic selective nerve root blocks is limited; whereas for lumbar provocation discography, it is fair. • The evidence for diagnostic lumbar facet joint nerve blocks and diagnostic sacroiliac intraarticular injections is good with 75% to 100% pain relief as criterion standard with controlled local anesthetic or placebo blocks. • The evidence is good in managing disc herniation or radiculitis for caudal, interlaminar, and transforaminal epidural injections; fair for axial or discogenic pain without disc herniation, radiculitis or facet joint pain with caudal, and interlaminar epidural injections, and limited for transforaminal epidural injections; fair for spinal stenosis with caudal, interlaminar, and transforaminal epidural injections; and fair for post surgery syndrome with caudal epidural injections and limited with transforaminal epidural injections. • The evidence for therapeutic facet joint interventions is good for conventional radiofrequency, limited for pulsed radiofrequency, fair to good for lumbar facet joint nerve blocks, and limited for intraarticular injections. • For sacroiliac joint interventions, the evidence for cooled radiofrequency neurotomy is fair; limited for intraarticular injections and periarticular injections; and limited for both pulsed radiofrequency and conventional radiofrequency neurotomy. • For lumbar percutaneous adhesiolysis, the evidence is fair in managing chronic low back and lower extremity pain secondary to post surgery syndrome and spinal stenosis. • For intradiscal procedures, the evidence for intradiscal electrothermal therapy (IDET) and biaculoplasty is limited to fair and is limited for discTRODE. • For percutaneous disc decompression, the evidence is limited for automated percutaneous lumbar discectomy (APLD), percutaneous lumbar laser disc decompression, and Dekompressor; and limited to fair for nucleoplasty for which the Centers for Medicare and Medicaid Services (CMS) has issued a noncoverage decision. II. Cervical Spine • The evidence for cervical provocation discography is limited; whereas the evidence for diagnostic cervical facet joint nerve blocks is good with a criterion standard of 75% or greater relief with controlled diagnostic blocks. • The evidence is good for cervical interlaminar epidural injections for cervical disc herniation or radiculitis; fair for axial or discogenic pain, spinal stenosis, and post cervical surgery syndrome. • The evidence for therapeutic cervical facet joint interventions is fair for conventional cervical radiofrequency neurotomy and cervical medial branch blocks, and limited for cervical intraarticular injections. III. Thoracic Spine • The evidence is limited for thoracic provocation discography and is good for diagnostic accuracy of thoracic facet joint nerve blocks with a criterion standard of at least 75% pain relief with controlled diagnostic blocks. • The evidence is fair for thoracic epidural injections in managing thoracic pain. • The evidence for therapeutic thoracic facet joint nerve blocks is fair, limited for radiofrequency neurotomy, and not available for thoracic intraarticular injections. IV. Implantables • The evidence is fair for spinal cord stimulation (SCS) in managing patients with failed back surgery syndrome (FBSS) and limited for implantable intrathecal drug administration systems. V. ANTICOAGULATION • There is good evidence for risk of thromboembolic phenomenon in patients with antithrombotic therapy if discontinued, spontaneous epidural hematomas with or without traumatic injury in patients with or without anticoagulant therapy to discontinue or normalize INR with warfarin therapy, and the lack of necessity of discontinuation of nonsteroidal anti-inflammatory drugs (NSAIDs), including low dose aspirin prior to performing interventional techniques. • There is fair evidence with excessive bleeding, including epidural hematoma formation with interventional techniques when antithrombotic therapy is continued, the risk of higher thromboembolic phenomenon than epidural hematomas with discontinuation of antiplatelet therapy prior to interventional techniques and to continue phosphodiesterase inhibitors (dipyridamole, cilostazol, and Aggrenox). • There is limited evidence to discontinue antiplatelet therapy with platelet aggregation inhibitors to avoid bleeding and epidural hematomas and/or to continue antiplatelet therapy (clopidogrel, ticlopidine, prasugrel) during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic fatalities. • There is limited evidence in reference to newer antithrombotic agents dabigatran (Pradaxa) and rivaroxan (Xarelto) to discontinue to avoid bleeding and epidural hematomas and are continued during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic events. CONCLUSIONS: Evidence is fair to good for 62% of diagnostic and 52% of therapeutic interventions assessed. DISCLAIMER: The authors are solely responsible for the content of this article. No statement on this article should be construed as an official position of ASIPP. The guidelines do not represent "standard of care."

Intrathecal infusion systems for long-term management of chronic non-cancer pain: an update of assessment of evidence.

BACKGROUND: Intrathecal infusion systems are often used for patients with intractable pain when all else fails, including surgery. There is, however, some concern as to the effectiveness and safety of this treatment. STUDY DESIGN:   A systematic review of intrathecal infusion systems for long-term management of chronic non-cancer pain. OBJECTIVE: To evaluate and update the effect of intrathecal infusion systems in managing chronic non-cancer pain. METHODS: The available literature on intrathecal infusion systems in managing chronic pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials and the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the U.S. Preventative Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to December 2012, and manual searches of the bibliographies of known primary and review articles. OUTCOME MEASURES: The primary outcome measure was pain relief with short-term relief < 12 months and long-term relief ≥ 12 months. Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. RESULTS: There were 28 studies identified for this systematic review. Of these, 21 were excluded from further review. A total of 7 non-randomized studies met inclusion criteria for methodological quality assessment. No randomized trials met the inclusion requirements.The evidence is limited based on observational studies. LIMITATIONS: The limitations of this systematic review include the paucity of literature. CONCLUSION: The evidence is limited for intrathecal infusion systems.

An update of evaluation of intravenous sedation on diagnostic spinal injection procedures.

BACKGROUND: Intravenous (IV) sedation analgesia is often employed in patients with chronic spinal pain undergoing diagnostic spinal injection procedures. The drugs used for intravenous sedation analgesia produce varying degrees of sedation, amnesia, anxiolysis, muscle relaxation, and analgesia. The very nature of these pharmacologic effects in altering the patient's level of consciousness, awareness, or response to a particular diagnostic stimulus invokes a sense of uncertainty about the results or response obtained from the diagnostic procedure. There is an ongoing controversy regarding the validity of controlled diagnostic blocks due to variability in sensitivity, specificity, and accuracy. Moreover, there is no consensus with regards to the use of sedation analgesic measures prior to controlled diagnostic blocks and their influence on the accuracy and validity of a diagnosis. OBJECTIVE: To assess and update the clinically significant effects sedation analgesia procedures have on the diagnostic accuracy and validity of interventional spinal techniques. METHODS: A comprehensive literature search using PubMed, EMBASE, and Cochrane Library review databases up to September 2012 was performed. The search included systematic and narrative review articles, prospective and retrospective studies, as well as cross-referencing of bibliographies from notable primary and review articles and abstracts from scientific meetings and peer-reviewed non-indexed journals. The search emphasized the effects of sedation analgesia on diagnostic spinal interventions. CONCLUSION: Based on a review of the available evidence, it appears that the administration of mild to moderate sedation does not confound the results or diagnostic validity of spinal injection procedures. Specifically, immediate pain relief after cervical and lumbar facet joint controlled nerve blocks is not enhanced by IV sedation with midazolam or fentanyl. This is especially true if stringent outcome criteria are employed, such as at least 75% pain relief combined with an increase in range of motion for pain limited movements.

Assessment of bleeding risk of interventional techniques: a best evidence synthesis of practice patterns and perioperative management of anticoagulant and antithrombotic therapy.

BACKGROUND: Interventional pain management is a specialty that utilizes invasive procedures to diagnose and treat chronic pain. Patients undergoing these treatments may be receiving exogenous anticoagulants and antithrombotics. Even though the risk of major bleeding is very small, the consequences can be catastrophic. However, the role of antithrombotic therapy for primary and secondary prevention of cardiovascular disease to decrease the incidence of acute cerebral and cardiovascular events is also crucial. Overall, there is a paucity of literature on the subject of bleeding risk in interventional pain management along with practice patterns and perioperative management of anticoagulant and anti-thrombotic therapy. STUDY DESIGN: Best evidence synthesis. OBJECTIVE: To critically appraise and synthesize the literature with assessment of the bleeding risk of interventional techniques including practice patterns and perioperative management of anticoagulant and antithrombotic therapy. METHODS: The available literature on the bleeding risk of interventional techniques and practice patterns and perioperative management of anticoagulant and antithrombotic therapy was reviewed. Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 through December 2012 and manual searches of the bibliographies of known primary and review articles. RESULTS: There is good evidence for the risk of thromboembolic phenomenon in patients who discontinue antithrombotic therapy, spontaneous epidural hematomas occur with or without traumatic injury in patients with or without anticoagulant therapy associated with stressors such as chiropractic manipulation, diving, and anatomic abnormalities such as ankylosing spondylitis, and the lack of necessity of discontinuation of nonsteroidal anti-inflammatory drugs (NSAIDs), including low dose aspirin prior to performing interventional techniques. There is fair evidence that excessive bleeding, including epidural hematoma formation may occur with interventional techniques when antithrombotic therapy is continued, the risk of thromboembolic phenomenon is higher than the risk of epidural hematomas with discontinuation of antiplatelet therapy prior to interventional techniques, to continue phosphodiesterase inhibitors (dipyridamole [Persantine], cilostazol [Pletal], and Aggrenox [aspirin and dipyridamole]), and that anatomic conditions such as spondylosis, ankylosing spondylitis and spinal stenosis, and procedures involving the cervical spine; multiple attempts; and large bore needles increase the risk of epidural hematoma; and rapid assessment and surgical or nonsurgical intervention to manage patients with epidural hematoma can avoid permanent neurological complications. There is limited evidence to discontinue antiplatelet therapy with platelet aggregation inhibitors to avoid bleeding and epidural hematomas and/or to continue antiplatelet therapy clopidogrel (Plavix), ticlopidine (Ticlid), or prasugrel (Effient) during interventional techniques to avoid cerebrovascular and cardiovascular thromboembolic fatalities. There is limited evidence in reference to newer antithrombotic agents dabigatran (Pradaxa) and rivaroxaban (Xarelto) to discontinue to avoid bleeding and epidural hematomas during interventional techniques and to continue to avoid cerebrovascular and cardiovascular thromboembolic events. RECOMMENDATIONS: The recommendations derived from the comprehensive assessment of the literature and guidelines are to continue NSAIDs and low dose aspirin, and phosphodiesterase inhibitors (dipyridamole, cilostazol, Aggrenox) during interventional techniques. However, the recommendations for discontinuation of antiplatelet therapy with platelet aggregation inhibitors (clopidogrel, ticlopidine, prasugrel) is variable with clinical judgment to continue or discontinue based on the patient's condition, the planned procedure, risk factors, and desires, and the cardiologist's opinion. Low molecular weight heparin (LMWH) or unfractionated heparin may be discontinued 12 hours prior to performing interventional techniques. Warfarin should be discontinued or international normalized ratio (INR) be normalized to 1.4 or less for high risk procedures and 2 or less for low risk procedures based on risk factors. It is also recommended to discontinue Pradaxa for 24 hours for paravertebral interventional techniques in 2 to 4 days for epidural interventions in patients with normal renal function and for longer periods of time in patients with renal impairment, and to discontinue rivaroxaban for 24 hours prior to performing interventional techniques. LIMITATIONS:   The paucity of the literature. CONCLUSION: Based on the available literature including guidelines, the recommendations in patients with antithrombotic therapy for therapy prior to interventional techniques are provided.

Considerations in selecting rapid-onset opioids for the management of breakthrough pain.

Breakthrough pain (BTP) is a transitory pain that occurs despite the use of long-term, around-the-clock analgesia. It is highly prevalent in certain populations and places a significant burden on patients, their families, caregivers, and health-care systems. Despite its prevalence and impact, BTP is sometimes unrecognized and often undertreated. Various formulations of fentanyl - a rapid-onset opioid with short duration of action - are available for the management of BTP. The efficacy of formulations using transmucosal, transbuccal, sublingual, and intranasal administration routes has been demonstrated for BTP treatment in clinical trials. However, a lack of head-to-head trials evaluating their relative efficacy makes it challenging for physicians to reach informed decisions on the most efficacious intervention for individual patients. In the absence of clear data on the relative efficacy of fentanyl formulations, prescribing decisions need to be based on physician understanding and experience and product cost and availability, taking into account the individual patient's needs, the ability of the patient or caregivers to administer medication, and the patient's wishes. This review evaluates current pharmacologic methods of alleviating BTP and discusses factors that should be considered when selecting the most appropriate formulation for individual patients. With the range of fentanyl formulations available, it is now possible to successfully address BTP in the majority of patients.

Botulinum toxins: mechanisms of action, antinociception and clinical applications.

Botulinum toxin (BoNT) is a potent neurotoxin that is produced by the gram-positive, spore-forming, anaerobic bacterium, Clostridum botulinum. There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G. Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150kDa, which is cleaved by tissue proteinases into an active di-chain molecule: a heavy chain (H) of ∼100 kDa and a light chain (L) of ∼50 kDa held together by a single disulfide bond. Each serotype demonstrates its own varied mechanisms of action and duration of effect. The heavy chain of each BoNT serotype binds to its specific neuronal ecto-acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs. The light chain acts to cleave SNAP-25, which inhibits synaptic exocytosis, and therefore, disables neural transmission. The action of BoNT to block the release of acetylcholine botulinum toxin at the neuromuscular junction is best understood, however, most experts acknowledge that this effect alone appears inadequate to explain the entirety of the neurotoxin's apparent analgesic activity. Consequently, scientific and clinical evidence has emerged that suggests multiple antinociceptive mechanisms for botulinum toxins in a variety of painful disorders, including: chronic musculoskeletal, neurological, pelvic, perineal, osteoarticular, and some headache conditions.

An updated review of the diagnostic utility of cervical facet joint injections.

BACKGROUND: Chronic persistent neck pain with or without upper extremity pain is common in the general adult population with a prevalence of 48% for women and 38% for men, with persistent complaints in 22% of women and 16% of men. Multiple modalities of treatment are exploding in managing chronic neck pain along with increasing prevalence. However, there is a paucity of evidence for all modalities of treatments in managing chronic neck pain. Controlled studies have supported the existence of cervical facet or zygapophysial joint pain in 36% to 60% in heterogenous population of these patients. However, these studies also have shown false-positive results in 27% to 63% of patients with a single diagnostic block. STUDY DESIGN: A systematic review of diagnostic cervical facet joint nerve blocks. OBJECTIVE: To evaluate and update the accuracy of diagnostic facet joint nerve blocks in the diagnosis of facet joint pain. METHODS: A methodological quality assessment of included studies was performed using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. Studies scoring less than 50% are presented descriptively and critically analyzed. The level of evidence was classified as good, fair, and limited or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF).Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to June 2012, and manual searches of the bibliographies of known primary and review articles. RESULTS: Overall, a total of 26 manuscripts were considered for diagnostic accuracy evaluation and 9 manuscripts for studies evaluating various factors influencing the diagnostic validity of facet joint interventions. Based on 9 studies meeting the inclusion criteria utilizing 75% to 100% pain relief as the criterion standard with controlled blocks, the evidence is good for diagnostic accuracy of cervical facet joint pain, with a prevalence of 36% to 60% with a false-positive rate of 27% to 63% with a single block. Based on 2 studies from the same group of authors, the evidence for 75% to 100% pain relief as the criterion standard with a single block is limited. The evidence is limited for a single diagnostic block with 50% to 74% pain relief as the criterion standard, whereas no studies were available assessing the accuracy of 50% to 74% pain relief as the criterion standard with controlled blocks. LIMITATIONS: The limitations of this systematic review include a paucity of literature on outcomes, randomized, placebo-controlled trials and a lack of consensus on a gold standard. CONCLUSIONS: Diagnostic cervical facet joint nerve blocks are safe, valid, and reliable. The strength of evidence for diagnostic facet joint nerve blocks is good with the utilization of controlled diagnostic blocks with at least 75% pain relief as the criterion standard; however, the evidence is limited for single blocks or dual blocks for relief of 50% to 74% and single blocks with at least 75% pain relief.