Aseptic Meningitis and Depression: The Neuropsychiatric Manifestations of a Patient with Systemic Lupus Erythematosus.

Aseptic meningitis as an initial and isolated manifestation of systemic lupus erythematosus (SLE) is extremely rare. About a third of patients with SLE have neuropsychiatric manifestations; however, less than 2% develop aseptic meningitis. Therefore, SLE as a cause of aseptic meningitis is commonly overlooked and leads to delayed or even missed diagnosis.

Editor's Highlight: Formulation and Toxicology Evaluation of the Intrathecal AYX1 DNA-Decoy in Sprague Dawley Rats.

The longevity of pain after surgery is debilitating and limits the recovery of patients. AYX1 is a double-stranded, unprotected, 23 base-pair oligonucleotide designed to reduce acute post-surgical pain and prevent its chronification with a single intrathecal perioperative dose. AYX1 mimics the DNA sequence normally bound by EGR1 on chromosomes, a transcription factor transiently induced in the dorsal root ganglia-spinal cord network following a noxious input.

Intrathecal administration of AYX2 DNA-decoy produces a long-term pain treatment in rat models of chronic pain by inhibiting the KLF6, KLF9 and KLF15 transcription factors.

Background: Nociception is maintained by genome-wide regulation of transcription in the dorsal root ganglia—spinal cord network. Hence, transcription factors constitute a promising class of targets for breakthrough pharmacological interventions to treat chronic pain. DNA decoys are oligonucleotides and specific inhibitors of transcription factor activities.

Pharmacology, pharmacokinetics, and metabolism of the DNA-decoy AYX1 for the prevention of acute and chronic post-surgical pain.

Background AYX1 is an unmodified DNA-decoy designed to reduce acute post-surgical pain and its chronification with a single intrathecal dose at the time of surgery. AYX1 inhibits the transcription factor early growth response protein 1, which is transiently induced at the time of injury and triggers gene regulation in the dorsal root ganglia and spinal cord that leads to long-term sensitization and pain. This work characterizes the AYX1 dose-response profile in rats and the link to AYX1 pharmacokinetics and metabolism in the cerebrospinal fluid, dorsal root ganglia, and spinal cord.

A Phase II Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Lenalidomide in Lumbar Radicular Pain with a Long-Term Open-Label Extension Phase.

Objective: This phase II study assessed lenalidomide efficacy and safety.

Design: Three-phase core study: 14-day prerandomization, 12-week treatment, and 52-week open-label extension.

Setting: Fourteen US centers from July 2005 to July 2007.

Lenalidomide for complex regional pain syndrome type 1: lack of efficacy in a phase II randomized study.

Unlabelled: Complex regional pain syndrome (CRPS) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury. Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide, we investigated lenalidomide, a thalidomide derivative, for CRPS treatment. We conducted a phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1.

Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury.

The persistence of pain after surgery increases the recovery interval from surgery to a normal quality of life. AYX1 is a DNA-decoy drug candidate designed to prevent post-surgical pain following a single intrathecal injection. Tissue injury causes a transient activation of the transcription factor EGR1 in the dorsal root ganglia-dorsal horn network, which then triggers changes in gene expression that induce neuronal hypersensitivity.

ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials.

Context: Development of pharmacological and behavioral interventions for cancer-related fatigue (CRF) requires adequate measures of this symptom. A guidance document from the Food and Drug Administration offers criteria for the formulation and evaluation of patient-reported outcome measures used in clinical trials to support drug or device labeling claims.

Methods: An independent working group, ASCPRO (Assessing Symptoms of Cancer Using Patient-Reported Outcomes), has begun developing recommendations for the measurement of symptoms in oncology clinical trials.

Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations.

There has been an increase in the number of chronic pain clinical trials in which the treatments being evaluated did not differ significantly from placebo in the primary efficacy analyses despite previous research suggesting that efficacy could be expected. These findings could reflect a true lack of efficacy or methodological and other aspects of these trials that compromise the demonstration of efficacy. There is substantial variability among chronic pain clinical trials with respect to important research design considerations, and identifying and addressing any methodological weaknesses would enhance the likelihood of demonstrating the analgesic effects of new interventions.

Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial.

Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment. Dexmethylphenidate (D-MPH; the D-isomer of methylphenidate) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment. A randomized, double-blind, placebo-controlled, parallel-group study evaluated the potential therapeutic effect and safety of D-MPH in the treatment of patients with chemotherapy-related fatigue.

Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials.

The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity.

Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations.

Unlabelled: A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures.

New and emerging pharmacological targets for neuropathic pain.

Increasing knowledge of the molecular consequences of nerve injury and the availability of genome databases has greatly increased the range of potential targets for the pharmacological management of neuropathic pain. Controlling neuronal sensitization and the associated alterations in gene expression, protein modification, and neuronal excitability is the key to managing neuropathic pain. Control of neuronal sensitization can occur through inhibition of nerve injury-associated production of cytokines, activation of glial cells, modulation of potassium channel subtypes, mitogen-activated protein kinases, the ubiquitin-proteasome system, or the protection and amplification of spinal cord dorsal horn inhibitory systems.

Core outcome domains for chronic pain clinical trials: IMMPACT recommendations.

Objective: To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment.

Methods: Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia, governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain.

Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat.

Streptozotocin (STZ)-induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy to assess the efficacies of potential analgesic agents. We have established this model, and here we question whether the changes in nocifensive reflex activity, used as a measure of hyperalgesia, are genuinely indicative of peripheral neuropathy or may rather be attributed to the extreme poor health of the animals. For comparison we have examined animals with peripheral neuropathy induced by partial ligation of the sciatic nerve.