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Biomedical subjects

Misha-Miroslav Backonja

Publications and source records attributed to Misha-Miroslav Backonja.

17 recordsLinked to original sources
PubMed2006

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. Our results confirm the clinical experience that groups of pain descriptors rather than single items differentiate between patients with neuropathic and non-neuropathic pain. The accuracy obtained by ANN analysis was only slightly higher than that of the traditional approaches, indicating the absence of nonlinear relationships in this dataset. Data analysis with ANNs provides a framework that extends what current approaches offer, especially for dynamic data, such as the rating of pain descriptors over time.

Adult↗
PubMed2006

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. MDT for neuropathic pain is based on a comprehensive clinical neuropathic pain assessment and ongoing monitoring of the drug therapy's efficacy and adverse effects, administering one drug at the time.

Analgesics↗
PubMed2006

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. When choosing treatment for patients with DPNP, physicians are confronted with a myriad of choices, none of which has been shown to be effective for all patients. This article reviews the evidence for these treatments and attempts to guide physicians in choosing those treatments based on evidence from well-designed clinical trials to support their use. Two agents, duloxetine and pregabalin, are formally approved by the Food and Drug Administration for the treatment of DPNP. In addition, several other agents, including the tricyclic class of antidepressants, have been effective in clinical trials. Ultimately, treatment choice must also Include consideration of adverse effects, individual patient factors such as comorbidities, and often cost.

Analgesics, Opioid↗
PubMed2006

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. METHODS: PARTICIPANTS underwent a series of quantitative sensory tests prior to, and seven days after the initiation of SCS trial. These tests included: vibration threshold (conducted using the VSA 3000; Medoc Inc., Ramat Ishay, Israel), cold threshold, warm threshold, heat pain threshold, phasic heat pain threshold, tonic heat pain threshold (conducted using the TSA 2001; Medoc Inc.), and electrical pain tolerance at 5, 250 and 2000 Hz (administered using the NerveScan 2000; Neurotron, Inc., Baltimore, MD, USA). RESULTS: Useful data were obtained from 12 patients. The results of the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz changed with an SCS trial. These results also correlated with the decision regarding the permanent implantation, which was made independently of them. In contrast, the results of thermal thresholds and tolerance to electrical stimulation at 2000 Hz tests did not change with the SCS trial. CONCLUSIONS: Our findings, which agree with those of a few other studies, suggest that the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz tests can assist the clinician to select the right patients for permanent stimulation.

Adolescent↗
PubMed2006

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). Minimum requirements for diagnosis of DPNP should include assessment of pain and symptoms and neurological examination, with the accent on sensory examination. Given that depression and other co-morbidities are commonly associated with this condition, a broad approach to management is essential. Lifestyle intervention and optimisation of glycaemic control are recommended as initial steps in management. An evidence-based treatment algorithm for DPNP has been proposed, recommending initial use of either a tricyclic antidepressant, selective serotonin noradrenaline re-uptake inhibitor or alpha-2-delta agonist, depending on patient co-morbidities and contra-indications. Addition of an opioid agonist may be required in the event of inadequate pain control. Irrespective of which treatment is offered, only about one third of patients are likely to achieve more than 50% pain relief. Further research to improve the diagnosis and management of DPNP is needed.

Anticonvulsants↗
PubMed2005

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. Stimuli were applied to distal and proximal sites in the upper and lower limbs of 50 healthy volunteers, ranging in age from 19 to 59 years. Thresholds for innocuous and noxious stimuli in this study were similar to previously published results. The mean pain rating across all sites at thresholds for noxious heat and cold stimuli was 4.10, as rated on a 0-10 numeric scale. Suggestions are provided for combining threshold information for innocuous and noxious stimuli and related pain ratings for the evaluation of sensory nervous system function and, specifically, neuropathic pain.

Adult↗
PubMed2004

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. To date, however, no neuroimaging studies have assessed these effects. We manipulated the subjects' belief that they had control over a nociceptive stimulus, while the stimulus itself was held constant. Using functional magnetic resonance imaging, we found that pain that was perceived to be controllable resulted in attenuated activation in the three neural areas most consistently linked with pain processing: the anterior cingulate, insular, and secondary somatosensory cortices. This suggests that activation at these sites is modulated by cognitive variables, such as perceived controllability, and that pain imaging studies may therefore overestimate the degree to which these responses are stimulus driven and generalizable across cognitive contexts.

Adult↗
PubMed2004

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. Ongoing average pain was rated as 5.7 and worst pain as 7.7 on 0 to 10 scale, and it was present in 96% of patients, whereas symptoms that are commonly studied in the laboratory, such as increased pain due to touch and due to heat, were much less frequent (64% and 38%, respectively). Worst pain was most highly correlated with shooting, stabbing, and distress symptom complex, which was in contrast to Average pain, which was most highly correlated with symptom complex consisting of a large number of items. Analysis of conceptually related thermal heat sensation types of pain, spontaneous "burning" pain and the evoked pain "increased due to heat," showed that spontaneous burning pain was reported at much higher frequency and intensity than the evoked increased pain due to heat. There was no statistically significant difference between descriptors from NPS and NPQ among subgroups of neuropathic pain, such as polyneuropathy, radiculopathy, or posttraumatic neuralgia, but this could be in part due to relatively small number of patients in these subgroups of neuropathic pain. Quantitative analysis, as performed in this study, is one of the steps in developing an approach for elucidating the relationship between neuropathic pain symptoms and underlying mechanisms. PERSPECTIVE: Assessment of neuropathic pain symptoms by means of specifically designed questionnaires provides significant insight into patients' pain experience, including pain overall, which is under many influences. Further research of this type can contribute to advances in mechanism-based diagnosis and treatment.

Adult↗
PubMed2004

Pharmacologic management part 1: better-studied neuropathic pain diseases.

Neuropathic pain impacts millions of people in the United States and around the world. Patients experience one of many symptoms, such as pain, paresthesia, dysesthesia, hyperalgesia, and allodynia, for many years because of unavailable or inadequate treatment. One of the major challenges in treating patients with neuropathic pain syndromes is a lack of consensus concerning the appropriate first-line treatment options for conditions associated with neuropathic pain, including postherpetic neuralgia, diabetic peripheral neuropathy, and trigeminal neuralgia. This review summarizes the published results of randomized trials involving treatment for neuropathic pain conditions. Anticonvulsants, such as gabapentin, carbamazepine, and lamotrigine, and tricyclic antidepressants, including amitriptyline and desipramine, have demonstrated efficacy in relieving pain associated with postherpetic neuralgia, diabetic peripheral neuropathy, and trigeminal neuralgia, in several studies. However, the lack of head-to-head comparison studies of these agents limits the conclusions that can be reached. Clinicians who must make decisions regarding the care of individual patients may find some guidance from the number of randomized trials with a positive outcome for each agent. Using quality-of-life study outcomes, treatment strategies must encompass the impact of therapeutic agents on the comorbid conditions of sleep disturbance and mood and anxiety disorders associated with neuropathic pain. Looking to the future, emerging therapies, such as pregabalin and newer N-methyl-D-aspartate-receptor blockers, may provide physicians and patients with new treatment options for more effective relief of pain.

Analgesics↗
PubMed2004

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. However, the results of published trials do support the use of anticonvulsants and/or tricyclic antidepressants as first-line pharmacotherapy in these three neuropathic pain syndromes. To maximize treatment outcomes, future research must: Continue to more fully elucidate the relationship between the signs and symptoms of pain and the underlying pathophysiology; Delineate the natural history of central poststroke pain, spinal cord injury, and complex regional pain syndrome; Identify patient-related factors that may indicate an increased risk of developing neuropathic pain following stroke or nerve injury; Investigate emerging treatments that target underlying pain mechanisms.

Analgesics↗
PubMed2003

Mechanistic stratification of antineuralgic agents.

Current treatment options in neuropathic pain include antidepressants, antiepileptics, antiarrhythmics, and analgesics. However, stratification of treatments based on their original therapeutic class is inadequate, as drugs belonging to a particular class may have distinct antineuralgic modes of action. It is therefore useful to review the mechanisms of action of these drugs and determine which of these mechanisms is most likely responsible for the drugs' efficacy in the symptomatic treatment of neuropathic pain. Switching from the traditional therapeutic class stratification to one based on putative antineuralgic mechanisms of action will allow more rational selection of therapies, and aid evaluation of the additive or synergistic effects of drugs when used in combination.

Analgesics↗
PubMed2003

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. This type of pain manifests not only with positive sensory phenomena such as pain, dysesthesia, and different types of hyperalgesia, but also with negative sensory phenomena and negative and positive motor and autonomic symptoms and signs.

Humans↗
PubMed2002

Use of anticonvulsants for treatment of neuropathic pain.

Emerging evidence from animal models of neuropathic pain suggests that many pathophysiologic and biochemical changes occur in the peripheral and central nervous system. Similarities between the pathophysiologic phenomena observed in some epilepsy models and in neuropathic pain models justify the use of anticonvulsants in the symptomatic management of neuropathic pain. Positive results from laboratory and clinical trials further support such use. Carbamazepine was the first of this class of drugs to be studied in clinical trials and has been longest in use for treatment of neuropathic pain. Clinical trial data support its use in treating trigeminal neuralgia, but data for treatment of painful diabetic neuropathy are less convincing. Use of newer anticonvulsants has marked a new era in the treatment of neuropathic pain. Gabapentin has demonstrated efficacy, specifically in painful diabetic neuropathy and postherpetic neuralgia. Lamotrigine has been reported to be effective in relieving pain from trigeminal neuralgia refractory to other treatments, HIV neuropathy, and central post-stroke pain. Results from clinical trials of phenytoin are equivocal. Zonisamide's mechanisms of action suggest that it would be effective in controlling neuropathic pain symptoms. Other anticonvulsants, including lorazepam, valproate, topiramate, and tiagabine, have also been under investigation. Anecdotal experience provides support for studies with oxcarbazepine and levetiracetam for treating neuropathic pain. Evidence supporting the efficacy of anticonvulsants in treatment of such pain is evolving. Additional clinical trials should provide information that will better define their role in neuropathic pain.

Acetates↗
PubMedDate not supplied

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. Of these, 149 had strictly neuropathic pain, while 233 had non-neuropathic pain. Subjects completed a 32 item preliminary questionnaire, which asked them to rate their usual pain on multiple descriptors, as well as the degree to which their pain differed in response to various internal and external factors. This preliminary questionnaire was submitted to factor analysis, and this yielded 6 factors. Representatives of each of these factors were combined with additional items that demonstrated significant differences between neuropathic and non-neuropathic pain groups, to yield a 12 item Neuropathic Pain Questionnaire (NPQ). These items were able to differentiate neuropathic pain patients from non-neuropathic pain patients in a holdout sample with 66.6% sensitivity and 74.4% specificity. The newly developed instrument, NPQ, may be used for the initial screening of neuropathic pain patients. It also has the ability to provide a quantitative measure for the descriptors important in the diagnosis and assessment of neuropathic pain. Consequently, it can be used for monitoring of neuropathic pain treatments and as an outcome measure.

Adult↗
PubMedDate not supplied

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 %]). Other measures were responder rate, adverse events, and correlation between lidocaine levels and PID %. RESULTS: There was a significant difference in the median PID % between the group treated with lidocaine 5 mg/kg/h (-34.60) and the placebo group (-11.96, P=0.012). Such effect began 4 hours after the onset of treatment and lasted until the end of the study. Lidocaine at lower infusion rates was no better than placebo in relieving pain. A modest but significant correlation was found between methylethylglycinexylidide (MEGX) levels and pain relief (R=0.60). There were no serious adverse events, but in two patients lidocaine was stopped prematurely. CONCLUSIONS: Lidocaine at 5 mg/kg/h was more effective than placebo at relieving neuropathic pain. The effect started 4 hours after the onset of treatment and continued for at least 4 hours after the end of the infusion. Additional research is needed using higher infusion rates with larger sample sizes to confirm these results and to explore the role of MEGX in the relief of neuropathic pain.

Adult↗