Yakov Vorobeychik

Combination therapy for neuropathic pain: a review of current evidence.

Neuropathic pain is a debilitating chronic condition that remains very difficult to treat. Recently, a number of clinical studies have compared the effectiveness of combination drug therapy with monotherapy for neuropathic pain treatment. In this article, we summarize up-to-date clinical studies of combination therapy for the treatment of both cancer- and non-cancer-related neuropathic pain. Despite a relatively small number of clinical studies on this topic, several positive indications have emerged. First, clinical studies using gabapentin (five positive trials) and pregabalin (five positive trials and one negative trial) in combination with an opioid, cyclo-oxygenase-2 inhibitor or antidepressant have shown positive responses greater than the respective monotherapies for pain related to diabetic neuropathy and post-herpetic neuropathy. Second, high-concentration (8%) topical capsaicin and a 5% lidocaine patch seem to be effective add-on therapies (a modality of combination therapy) for various neuropathic pain conditions. Third, combination therapy for cancer-related neuropathic pain has yielded only limited success based on a number of small-scale clinical studies.While there are benefits of using combination therapy for neuropathic pain treatment, including better pain relief and reduced adverse effects, more clinical studies are required in order to (i) make head-to-head comparisons between combination and single-drug therapies, (ii) identify symptom-specific combination therapies for distinctive clinical neuropathic pain conditions, (iii) explore combination therapies that include non-drug modalities such as physical therapy, psychological coping and biofeedback to facilitate functional restoration and (iv) develop new and objective evaluation tools for clinical outcome assessment.

Improved Opioid Analgesic Effect Following Opioid Dose Reduction

INTRODUCTION Traditionally, opioids have been the cornerstone of therapy for patients suffering from cancer pain, regardless of the potential to develop opioid tolerance. In chronic pain patients who experience worsening pain despite increasing doses of opioids, the clinical role of opioid-induced hyperalgesia is gaining more recognition. CASE Presented here is the case of a 56-year-old man with recurrent squamous cell lung carcinoma and spinal metastases, suffering with intractable 8/10 pain on the visual analog scale in his chest, lower thoracic spine, and upper lumbar spine. He was admitted five times for pain control. In spite of escalating doses of oxycodone, morphine, and hydromorphone, the patient continued to experience severe pain. Also, he endured undesirable sedation, fatigue, and generalized weakness. The clinical picture suggested the possibility of opioid-induced hyperalgesia. We decreased the hydromorphone dose by 40-50% and started methadone. The patients pain level dropped to a more acceptable 3/10. He was more alert, and his pain was tolerable until his death. DISCUSSION Opioid-induced hyperalgesia might be considered in a patient who has no evidence of disease progression, who is on clinically reasonable doses of opioids, and whose pain escalates as opioid doses are increased. A reduction of opioids and the addition of a low-dose N-methyl-D-aspartate receptor antagonist may provide a favorable clinical outcome in those patients who have failed to benefit from opioid rotation and other adjunctive pain treatments.

Epidural steroid injections, conservative treatment, or combination treatment for cervical radicular pain: a multicenter, randomized, comparative-effectiveness study.

Background:Cervical radicular pain is a major cause of disability. No studies have been published comparing different types of nonsurgical therapy. Methods:A comparative-effectiveness study was performed in 169 patients with cervical radicular pain less than 4 yr in duration. Participants received nortriptyline and/or gabapentin plus physical therapies, up to three cervical epidural steroid injections (ESI) or combination treatment over 6 months. The primary outcome measure was average arm pain on a 0 to 10 scale at 1 month. Results:One-month arm pain scores were 3.5 (95% CI, 2.8 to 4.2) in the combination group, 4.2 (CI, 2.8 to 4.2) in ESI patients, and 4.3 (CI, 2.8 to 4.2) in individuals treated conservatively (P = 0.26). Combination group patients experienced a mean reduction of −3.1 (95% CI, −3.8 to −2.3) in average arm pain at 1 month versus −1.8 (CI, −2.5 to −1.2) in the conservative group and −2.0 (CI, −2.7 to −1.3) in ESI patients (P = 0.035). For neck pain, a mean reduction of −2.2 (95% CI, −3.0 to −1.5) was noted in combination patients versus −1.2 (CI, −1.9 to −0.5) in conservative group patients and −1.1 (CI, −1.8 to −0.4) in those who received ESI; P = 0.064). Three-month posttreatment, 56.9% of patients treated with combination therapy experienced a positive outcome versus 26.8% in the conservative group and 36.7% in ESI patients (P = 0.006). Conclusions:For the primary outcome measure, no significant differences were found between treatments, although combination therapy provided better improvement than stand-alone treatment on some measures. Whereas these results suggest an interdisciplinary approach to neck pain may improve outcomes, confirmatory studies are needed.

Epidural steroid injections compared with gabapentin for lumbosacral radicular pain: multicenter randomized double blind comparative efficacy study

Objective To evaluate whether an epidural steroid injection or gabapentin is a better treatment for lumbosacral radiculopathy. Design A multicenter randomized study conducted between 2011 and 2014. Computer generated randomization was stratified by site. Patients and evaluating physicians were blinded to treatment outcomes. Settings Eight military, Veterans Administration, and civilian hospitals. Participants 145 people with lumbosacral radicular pain secondary to herniated disc or spinal stenosis for less than four years in duration and in whom leg pain is as severe or more severe than back pain. Interventions Participants received either epidural steroid injection plus placebo pills or sham injection plus gabapentin. Main outcome measures Average leg pain one and three months after the injection on a 0-10 numerical rating scale. A positive outcome was defined as a ≥2 point decrease in leg pain coupled with a positive global perceived effect. All patients had one month follow-up visits; patients whose condition improved remained blinded for their three month visit. Results There were no significant differences for the primary outcome measure at one month (mean pain score 3.3 (SD 2.6) and mean change from baseline −2.2 (SD 2.4) in epidural steroid injection group versus 3.7 (SD 2.6) and −1.7 (SD 2.6) in gabapentin group; adjusted difference 0.4, 95% confidence interval −0.3 to 1.2; P=0.25) and three months (mean pain score 3.4 (SD 2.7) and mean change from baseline −2.0 (SD 2.6) versus 3.7 (SD 2.8) and −1.6 (SD 2.7), respectively; adjusted difference 0.3, −0.5 to 1.2; P=0.43). Among secondary outcomes, one month after treatment those who received epidural steroid injection had greater reductions in worst leg pain (−3.0, SD 2.8) than those treated with gabapentin (−2.0, SD 2.9; P=0.04) and were more likely to experience a positive successful outcome (66% v 46%; number needed to treat=5.0, 95% confidence interval 2.8 to 27.0; P=0.02). At three months, there were no significant differences between treatments. Conclusions Although epidural steroid injection might provide greater benefit than gabapentin for some outcome measures, the differences are modest and are transient for most people. Trial registration ClinicalTrials.gov Identifier: NCT01495923.

Epidural Steroid Injections are Safe and Effective: Multisociety Letter in Support of the Safety and Effectiveness of Epidural Steroid Injections

BACKGROUND In April 2014, the Food and Drug Administration (FDA) issued a Drug Safety Communication requesting that corticosteroid labeling include warnings that injection of corticosteroids into the epidural space of the spine may result in rare but serious adverse events, including loss of vision, stroke, paralysis, and death. RESULTS The International Spine Intervention Society spearheaded a collaboration of more than a dozen other medical societies in submitting the letter below to the FDA on November 7, 2014. We are publishing the letter to ensure that the readership of Pain Medicine is aware of the multisociety support for the safety and effectiveness of these procedures. A special note of thanks to all of the societies who signed on in support of the message.

Incidence of Neuropathic Pain after Cooled Radiofrequency Ablation of Sacral Lateral Branch Nerves

OBJECTIVE To determine the incidence of neuropathic pain after cooled radiofrequency ablation (RFA) of the sacral lateral branches for the treatment of chronic posterior sacroiliac joint complex pain. DESIGN Retrospective chart review of all patients with chronic posterior sacroiliac joint complex pain who underwent cooled RFA of the sacral lateral branches in our practice between July 2011 and February 2014. SETTING Single academic pain practice at a tertiary care medical center. SUBJECTS Thirty-six patients with chronic posterior sacroiliac joint complex pain. METHODS All charts were reviewed to determine the procedure date, unilateral or bilateral, number of levels treated, and number of individual lesions. Side effects were assessed for their presence or absence, character, intensity, duration, and whether treatment was initiated or symptoms resolved spontaneously. RESULTS Forty-eight separate procedures were performed, with a total of 193 levels and 430 lesions. Three patients had transient postprocedure neuropathic pain yielding a 0.7% (95% confidence interval [CI]± 0.4%) rate of this complication per lesion. This proportion increases to 6.2% (95% CI ± 3.5%) per procedure and to 9.4% (95% CI ± 5.2%) per patient. CONCLUSION The incidence of postprocedural neuropathic pain after cooled RFA for posterior sacroiliac joint complex denervation is low and in a similar range to that in the lumbar spine. We consider this procedure safe to be utilized by pain medicine practitioners.

Radiofrequency Denervation for Chronic Low Back Pain

tail chains. Even when contraception is available in pharmacies, it may not be economically accessible because of fees. In California, lack of insurance reimbursement may undergird low availability of pharmacist-prescribed contraception. Additional legislation (effective in July 2017) requires Californias Medicaid program to reimburse for pharmacist services by July 20216; the implementation timeline and lack of private insurance coverage may still present barriers to increasing availability of this service. The strengths of this study include use of a large, representative sample of pharmacies and the high response rate. Limitations are assessment of service availability via phone and inclusion of only 1 state. Additionally, availability of each method was not systematically ascertained. Pharmacist-prescribed contraception could facilitate contraceptive use for many women. With at least 9 states implementing or considering allowing pharmacist-prescribed contraception,1 continued research is needed to identify barriers to accessibility of this clinical service.

The Effectiveness and Risks of Non–Image-Guided Lumbar Interlaminar Epidural Steroid Injections: A Systematic Review with Comprehensive Analysis of the Published Data

OBJECTIVE To determine the effectiveness and risks of non-image-guided lumbar interlaminar epidural steroid injections. DESIGN Systematic review. INTERVENTIONS Three reviewers with formal training and certification in evidence-based medicine searched the literature on non-image-guided lumbar interlaminar epidural steroid injections. A larger team of seven reviewers independently assessed the methodology of studies found and appraised the quality of the evidence presented. OUTCOME MEASURES The primary outcome assessed was pain relief. Other outcomes such as functional improvement, reduction in surgery rate, decreased use of opioids, and complications were noted, if reported. The evidence was appraised in accordance with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system of evaluating evidence. RESULTS The searches yielded 92 primary publications addressing non-image-guided lumbar interlaminar epidural steroid injections. The evidence supporting the effectiveness of these injections for pain relief and functional improvement in patients with lumbar radicular pain due to disc herniation or neurogenic claudication secondary to lumbar spinal stenosis is limited. This procedure may provide short-term benefit in the first 3-6 weeks. The small number of case reports on significant risks suggests these injections are relatively safe. In accordance with GRADE, the quality of evidence is very low. CONCLUSIONS In patients with lumbar radicular pain secondary to disc herniation or neurogenic claudication due to spinal stenosis, non-image-guided lumbar interlaminar epidural steroid injections appear to have clinical effectiveness limited to short-term pain relief. Therefore, in a contemporary medical practice, these procedures should be restricted to the rare settings where fluoroscopy is not available.

NMDA Receptor Antagonists in the Treatment of Pain

Over the past three decades, the central glutamatergic system, particularly the role of the N-methyl-d-aspartate (NMDA) receptor in the neural mechanisms of persistent pain, has been extensively investigated. Chronic pain can be sustained by way of a central sensitization process involving the NMDA receptor system. Data from preclinical studies have consistently supported a crucial role of the central glutamatergic system and NMDA receptors in the induction and maintenance of persistent pain resulting from pathological conditions such as inflammation and nerve injury. To date, clinical trials have resulted in mixed conclusions as to the overall effectiveness in treating persistent pain with NMDA receptor antagonists. Nonetheless, NMDA receptor antagonists have been demonstrated as an effective treatment option in the management of chronic pain, particularly for pain which has been refractory to other treatment modalities.

Authors' reply to Lin and colleagues.

Lin and colleagues commented that because the differences between treatments were small we were unjustified in recommending one treatment over another.1 2 In our conclusions we stated that it was reasonable to proceed with pharmacotherapy first, given the small differences seen. If physical therapy and surgery—which is associated with much higher costs and risks than physical therapy—were shown to be equivalent, would they still state …