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 alpha 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-alpha 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.

The intravenous ketamine test predicts subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients.

UNLABELLED: Fibromyalgia (FM) is a challenging pain syndrome for which no reliable pharmacologic treatment exists. Recent clinical studies suggest that N-methyl-D-aspartate receptors might play a role in the pathogenesis of this disorder. To determine whether an intravenous (IV) ketamine test predicts the response to a therapeutic trial with an oral N-methyl-D-aspartate receptor antagonist, we performed a low-dose (0.1 mg/kg) IV ketamine infusion on 34 consecutive patients with FM, which was subsequently followed by an oral dextromethorphan (DX) treatment regimen. As per previous guidelines, the cutoff value for a positive response to the IV ketamine test was designated to be 67% pain relief, and a positive response to DX treatment was 50% pain reduction at 4- to 6-week follow-up visits. The degree of correlation between pain relief with ketamine and DX was highly significant (Pearson correlation coefficient, 0.66; P < .001). Ten patients responded positively to both ketamine and DX, 19 responded to neither drug, 3 had a positive response to ketamine but not DX, and 2 obtained good pain relief with DX but not ketamine. The sensitivity of the IV ketamine test was 83%, the specificity was 86%, the positive predictive value was 77%, and the negative predictive value was 91%. An association was also found between the development of side effects to the two treatments. PERSPECTIVE: The response to an IV ketamine infusion was found to predict the subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients, with an observed agreement of 83%. Considering the refractory nature of fibromyalgia to conventional pain treatments, the IV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials.