Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations.

A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development.

NGX-4010, a high-concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double-blind, controlled study with an open-label extension.

Objectives: To assess the efficacy, tolerability, and safety of NGX-4010, a high-concentration capsaicin dermal patch (capsaicin 640 microg/cm(2), 8%) in patients with postherpetic neuralgia (PHN).

Methods: Patients were randomized to receive NGX-4010 or control patch in a 4-week, double-blind study. This was followed by an open-label extension phase (up to 48 weeks total) where patients could receive up to three additional treatments no sooner than 12 weeks after initial treatment.

Assessment of neuropathic pain in primary care.

Management of patients presenting with chronic pain is a common problem in primary care. Essentially, the classification of chronic pain falls into 3 broad categories: (1) pain owing to tissue disease or damage (nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3) pain without a known somatic background. Key challenges in developing a targeted holistic approach to treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and assessing the relative importance of its various components; and determining appropriate treatment.

Quantitative sensory testing and mapping: a review of nonautomated quantitative methods for examination of the patient with neuropathic pain.

Objectives: Despite a growing interest in neuropathic pain, neurologists and pain specialists do not have a standard, validated, office examination for the evaluation of neuropathic pain signs to complement the neurologic, musculoskeletal, and general physical examinations. An office neuropathic pain examination focused on quantifying sensory features of neuropathic pain, ranging from deficits to allodynia and hyperalgesia, and evoked by a physiologically representative array of stimuli, will be an essential tool to monitor treatment effectiveness and for clinical investigation into the mechanisms and management of neuropathic pain. Such an examination should include mapping of areas of stimulus-evoked neuropathic pain and standardized, reproducible quantitative sensory testing (QST) of tactile, punctuate, pressure, and thermal modalities.

A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain.

ABT-594 is a neuronal nicotinic acetylcholine receptor (NNR) agonist that exhibits potent analgesic activity in preclinical models of acute, chronic, and neuropathic pain. The purpose of this phase 2, randomized, multicenter, double-blind, placebo-controlled study was to evaluate the safety and analgesic efficacy of ABT-594 in patients with diabetic peripheral neuropathic pain (DPNP). A total of 266 DPNP patients were randomized 1:1:1:1 to receive placebo, ABT-594 150 microg BID, ABT-594 225 microg BID, or ABT-594 300 microg BID.

Voluntary facial displays of pain increase suffering in response to nociceptive stimulation.

Unlabelled: Facial expressions of pain are an important part of the pain response, signaling distress to others and eliciting social support. To evaluate how voluntary modulation of this response contributes to the pain experience, 29 subjects were exposed to thermal stimulation while making standardized pain, control, or relaxed faces. Dependent measures were self-reported negative effect (valence and arousal) as well as the intensity of nociceptive stimulation required to reach a given subjective level of pain.

Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicenter, randomized, double-blind, placebo-controlled, parallel-group studies.

Objective: This post hoc analysis was aimed to summarize the efficacy and tolerability of duloxetine as represented by number needed to treat (NNT) and number needed to harm (NNH) to provide a clinically useful assessment of the position of duloxetine among current agents used to treat diabetic peripheral neuropathic pain (DPNP).

Methods: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as >or=30% and >or=50% reductions from baseline in the weekly mean of the 24-hour average pain severity scores); NNH was calculated based on rates of discontinuation due to adverse events (AEs).

Individual differences in the effects of perceived controllability on pain perception: critical role of the prefrontal cortex.

The degree to which perceived controllability alters the way a stressor is experienced varies greatly among individuals. We used functional magnetic resonance imaging to examine the neural activation associated with individual differences in the impact of perceived controllability on self-reported pain perception. Subjects with greater activation in response to uncontrollable (UC) rather than controllable (C) pain in the pregenual anterior cingulate cortex (pACC), periaqueductal gray (PAG), and posterior insula/SII reported higher levels of pain during the UC versus C conditions.

Long-term use of controlled-release oxycodone for noncancer pain: results of a 3-year registry study.

Objective: To evaluate the outcomes associated with the use of controlled-release (CR) oxycodone for up to 3 years in the treatment of noncancer pain.

Methods: Adult patients who previously participated in controlled trials of CR oxycodone for osteoarthritis pain, diabetic neuropathy pain, or low back pain, and who continued to require opioid analgesia for moderate or severe pain, were enrolled in an open-label, uncontrolled, registry study. Data collected over time included dose, pain severity on a numeric scale, treatment acceptability, adverse events, and descriptions of problematic drug-related behavior.

Assessment: use of epidural steroid injections to treat radicular lumbosacral pain: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

Based on the available evidence, the Therapeutics and Technology Assessment subcommittee concluded that 1) epidural steroid injections may result in some improvement in radicular lumbosacral pain when assessed between 2 and 6 weeks following the injection, compared to control treatments (Level C, Class I-III evidence). The average magnitude of effect is small and generalizability of the observation is limited by the small number of studies, highly selected patient populations, few techniques and doses, and variable comparison treatments; 2) in general, epidural steroid injection for radicular lumbosacral pain does not impact average impairment of function, need for surgery, or provide long-term pain relief beyond 3 months. Their routine use for these indications is not recommended (Level B, Class I-III evidence); 3) there is insufficient evidence to make any recommendation for the use of epidural steroid injections to treat radicular cervical pain (Level U).

Quantitative sensory testing for spinal cord stimulation in patients with chronic neuropathic pain.

Objective: A prospective pilot study was conducted, attempting to identify objective tests that would help clinicians to assess the efficacy of spinal cord stimulation (SCS) trial preceding permanent device implantation.

Setting: Four university hospitals in the United States and Israel.

Participants: Thirteen patients with radicular leg pain due to failed back surgery syndrome (FBSS) or leg pain due to complex regional pain syndrome (CRPS) who were candidates for SCS.

New perspectives on the management of diabetic peripheral neuropathic pain.

Peripheral neuropathy affects about 30% of people with diabetes mellitus. Between 16% and 26% of diabetes patients experience chronic pain. This may be referred to as diabetic neuropathic pain (DNP) or diabetic peripheral neuropathic pain (DPNP).

Classification of patients with pain based on neuropathic pain symptoms: comparison of an artificial neural network against an established scoring system.

Wider use of pain assessment tools that are specifically designed for certain types of pain--such as neuropathic pain--contribute an increasing amount of information which in turn offers the opportunity to employ advanced methods of data analysis. In this manuscript, we present the results of a study where we employed artificial neural networks (ANNs) in an analysis of pain descriptors with the goal of determining how an approach that uses a specific symptoms-based tool would perform with data from the real world of clinical practice. We also used traditional statistics approaches in the form of established scoring systems as well as logistic regression analysis for the purpose of comparison.

Consensus guidelines: treatment planning and options. Diabetic peripheral neuropathic pain.

Despite the number of patients affected by diabetic peripheral neuropathic pain (DPNP), little consensus exists about the pathophysiology, best diagnostic tools, and primary treatment choices. Theories about the causes of DPNP are inextricably linked with the causes of diabetic neuropathles, yet most patients with such neuropathies do not experience pain. The factors that differentiate patients with pain from those without remain unknown and are the subject of much research.

A randomized, double-masked, placebo-controlled pilot trial of extended IV lidocaine infusion for relief of ongoing neuropathic pain.

Objectives: To determine the dose-response effect and safety of IV lidocaine at different dose infusion rates on spontaneous ongoing neuropathic pain.

Methods: In this double-masked, placebo-controlled, parallel study conducted in an outpatient clinical research center, patients with peripheral neuropathic pain received a 6-hour infusion of three doses (1, 3, and 5 mg/kg) of lidocaine or placebo. The main outcome measure was relief of pain intensity (percentage pain intensity difference [PID %]).

Rational multidrug therapy in the treatment of neuropathic pain.

Multidrug therapy (MDT) has been widely accepted and used as a standard of practice in most areas of medical practice, including neuropathic pain. Because neuropathic pain is a new field of medical science and practice, standards for its treatment including MDT are still evolving. In this article, we present rationale and principals for the MDT of neuropathic pain based on our best understandings of the underlying mechanisms of the disease processes and the actions of drugs, the goal being to maximize benefits and minimize adverse effects.

Pain ratings at the thresholds are necessary for interpretation of quantitative sensory testing.

Published databases of quantitative sensory testing (QST) for sensory thresholds provide a means for detecting deficits of the thermonociceptive sensory nervous system. These databases, however, do not assist in the assessment of neuropathic pain, which is characterized by pain or hyperalgesia, or both. We utilized the method of levels for innocuous thermal stimuli, warm and cool, and the method of limits for noxious thermal stimuli, hot pain and cold pain, to determine QST thresholds.

Neuropathic pain symptoms relative to overall pain rating.

Unlabelled: The influence of sensory symptoms on overall simple pain ratings in neuropathic pain is not well understood. The goal of this study was to determine this relationship by using the Neuropathic Pain Questionnaire (NPQ) and Neuropathic Pain Scale (NPS) in patients who had neuropathic pain. Overall pain intensity ratings were assessed by means of Average and Worst Pain ratings from the Brief Pain Inventory.

Perceived controllability modulates the neural response to pain.

The response to painful stimulation depends not only on peripheral nociceptive input but also on the cognitive and affective context in which pain occurs. One contextual variable that affects the neural and behavioral response to nociceptive stimulation is the degree to which pain is perceived to be controllable. Previous studies indicate that perceived controllability affects pain tolerance, learning and motivation, and the ability to cope with intractable pain, suggesting that it has profound effects on neural pain processing.

Pharmacologic management part 2: lesser-studied neuropathic pain diseases.

This second part of a review of the pharmacologic management of neuropathic pain diseases describes the current treatment options for three lesser-studied neuropathic syndromes: Central poststroke pain, spinal cord injury, and complex regional pain syndrome II. Diagnosis can be difficult in patients with these syndromes, because the pain experienced is much greater and of a different type than would normally be expected following a stroke or injury to the spinal cord or a peripheral nerve. Even when an accurate and timely diagnosis is made, treatment options are limited and frequently suboptimal.

Development of a neuropathic pain questionnaire.

Ongoing efforts to develop mechanisms-based assessment and treatment of chronic pain have been hindered by the lack of assessment tools differentially sensitive to various phenomena underlying different mechanisms of pain. This study describes the development of an assessment instrument intended to measure neuropathic pain based on qualities of pain as they are inferred from pain descriptors. Subjects were 528 chronic pain patients from several clinics.

Defining neuropathic pain.

Clinical research and practice have suffered because of lack of specificity when clinical diagnoses of pain are made. Distinction between neuropathic and inflammatory pain mechanisms is suggested, as well as the distinction between neuropathic pain from hypersensitivity pain disorders, previously termed neuropathic pain due to neurological dysfunction. Neuropathic pain is in this case defined as pain occurring in the ara of body affected by neurological disease or injury.