Management Of Peripheral Neuropathic Pain Research Articles

A Review on the Management of Peripheral Neuropathic Pain Following Breast Cancer.

Postmastectomy pain syndrome (PMPS) is a common and debilitating form of postsurgical pain with neuropathic characteristics, presenting as burning, stabbing, or pulling sensations after mastectomy, lumpectomy, or other breast procedures. With a prevalence of 31%, the risk factors for PMPS include younger age, psychosocial factors, radiotherapy, axillary lymph node dissection, and a history of chronic pain. This review evaluates the pharmacological and surgical options for managing PMPS. Pharmacological treatment options include antidepressants, gabapentinoids, levetiracetam, capsaicin, and topical lidocaine. Procedural and surgical options include fat grafting, nerve blocks, radiofrequency ablation, peripheral nerve surgery, serratus plane block, and botulinum toxin injections. Despite the variety of therapeutic options available for patients, further randomized trials are required to conclude whether these treatments reduce the intensity of neuropathic pain in patients with PMPS. In particular, comparative studies and the inclusion of patients across a range of pain intensities will be essential to developing a treatment algorithm for PMPS. In conclusion, current management for these patients should be tailored to their individual requirements.

Exploring Cholinergic Compounds for Peripheral Neuropathic Pain Management: A Comprehensive Scoping Review of Rodent Model Studies.

Neuropathic pain affects about 7-8% of the population, and its management still poses challenges with unmet needs. Over the past decades, researchers have explored the cholinergic system (muscarinic and nicotinic acetylcholine receptors: mAChR and nAChR) and compounds targeting these receptors as potential analgesics for neuropathic pain management. This scoping review aims to provide an overview of studies on peripheral neuropathic pain (PNP) in rodent models, exploring compounds targeting cholinergic neurotransmission. The inclusion criteria were original articles on PNP in rodent models that explored the use of compounds directly targeting cholinergic neurotransmission and reported results of nociceptive behavioral assays. The literature search was performed in the PubMed and Web of Science databases (1 January 2000-22 April 2023). The selection process yielded 82 publications, encompassing 62 compounds. The most studied compounds were agonists of α4β2 nAChR and α7 nAChR, and antagonists of α9/α10 nAChR, along with those increasing acetylcholine and targeting mAChRs. Studies mainly reported antinociceptive effects in traumatic PNP models, and to a lesser extent, chemotherapy-induced neuropathy or diabetic models. These preclinical studies underscore the considerable potential of cholinergic compounds in the management of PNP, warranting the initiation of clinical trials.

Scyphocephalione A isolated from the stem bark of Scyphocephalium ochocoa (Myristicaceae) attenuate acute and chronic pain through the antiinflammatory activity.

In the treatment of cancer, patients that receive anti-cancer drugs such as Vincristine develop peripheral neuropathic pain. Scyphocephalione A is a new bioactive compound isolated from Scyphocephalium ochocoa (Myristicaceae), a medicinal plant traditionally used in African countries. Recently, an in vitro study has shown its anti-inflammatory and cytotoxic activities on MCF-7 cell line of mammary carcinoma. The purpose of the present study was to assess the in vitro anti-inflammatory and in vivo anti-nociceptive activities of Scyphocephalione A. In vitro tests were carried out on cyclooxygenase and 5-lipoxygenase activities, and on protein denaturation; while in vivo tests were performed on acute and chronic pain models. It was noticed that Scyphocephalione A (1000µg/ml), inhibits proteins denaturation, cyclooxygenase and 5-lipoxygenase activities respectively by 74.21%, 75.80% and 64.43%. The dose 50mg/kg of Scyphocephalione A, inhibits acetic acid (63.43%, p < 0.001) and formalin (42.12%, p < 0.001) within first phase and 67.53% (p < 0.001) within second phase)-induced pains. At the same dose, Scyphocephalione A significantly inhibited mechanical and heat hyperalgesia, as well as cold allodynia induced by vincristine. In addition, the compound restored haematological, biochemical and oxidative stress parameters which were altered following Vincristine administration. These results suggest that Scyphocephalione A is endowed with anti-inflammatory potential and antinociceptive properties. Therefore, Scyphocephalione A can be classified as a promising molecule for the management of peripheral neuropathic pain triggered by anti-cancer drug.

Efficacy and safety of botulinumA toxin for the treatment of chronic peripheral neuropathic pain: A systematic review of randomized controlled trials and meta-analysis.

Botulinum toxin type A (BTX-A)is a recently developed treatment for the management of peripheral neuropathic pain. The objective of this study was to provide a synthesis of the evidence concerning the efficacy and safety of subcutaneous botulinum toxin type A injections. We searched the MEDLINE, EMBASE, LILACS, Cochrane, and Clinical Trial Register databases for randomized controlled trials comparingsubcutaneousBTX-A to placebo injections for treating chronic peripheral neuropathic pain. The primary endpoint was the assessment of pain 1month after the injection. The secondary outcomes were the assessment of pain at 3months, neuropathic pain intensity andquality of lifeat 1 and 3months, and adverse effects. A random-effect meta-analysis was performed on the combined data. Evidence quality was rated by the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Ten randomized controlled trials including 505 patients were included in this review (registration number CRD42021239108). At 1 and 3months after injection,theBTX-A groups had a lower mean difference (MD) in pain score (MD -1.87 (confidence intervals [CIs] -2.91; -0.83) and -1.38 (CI -1.95; -0.81), respectively).Subgroup analysis showed greater efficacy for diabetic polyneuropathy (MD -2.48, [-3.22; -1.74]).We found no impact ofBTX-A onquality of life and no difference in adverse effect betweenBTX-A andplacebo.The evidencewasconsideredof moderate quality. The pooled data suggest that subcutaneousBTX-A injections have aclinicallysignificant effect, decreasing pain for threemonths after the injection, but nobenefit in terms of quality of life has yet been demonstrated. We found that botulinum toxin is efficient and safe for the treatment of neuropathic pain, especially for diabetic polyneuropathy. Botulinum toxin type A, used for years in neurology, rehabilitation and physical medicine, has proved innocuous and effective, and should be considered as a serious alternative for pain treatment.

Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.

Neuropathic pain in humans results from an injury or disease of the somatosensory nervous system at the peripheral or central level. Despite the considerable progress in pain management methods made to date, peripheral neuropathic pain significantly impacts patients’ quality of life, as pharmacological and non-pharmacological methods often fail or induce side effects. Topical treatments are gaining popularity in the management of peripheral neuropathic pain, due to excellent safety profiles and preferences. Moreover, topical treatments applied locally may target the underlying mechanisms of peripheral sensitization and pain. Recent studies showed that peripheral sensitization results from interactions between neuronal and non-neuronal cells, with numerous signaling molecules and molecular/cellular targets involved. This narrative review discusses the molecular/cellular mechanisms of drugs available in topical formulations utilized in clinical practice and their effectiveness in clinical studies in patients with peripheral neuropathic pain. We searched PubMed for papers published from 1 January 1995 to 30 November 2020. The key search phrases for identifying potentially relevant articles were “topical AND pain”, “topical AND neuropathic”, “topical AND treatment”, “topical AND mechanism”, “peripheral neuropathic”, and “mechanism”. The result of our search was 23 randomized controlled trials (RCT), 9 open-label studies, 16 retrospective studies, 20 case (series) reports, 8 systematic reviews, 66 narrative reviews, and 140 experimental studies. The data from preclinical studies revealed that active compounds of topical treatments exert multiple mechanisms of action, directly or indirectly modulating ion channels, receptors, proteins, and enzymes expressed by neuronal and non-neuronal cells, and thus contributing to antinociception. However, which mechanisms and the extent to which the mechanisms contribute to pain relief observed in humans remain unclear. The evidence from RCTs and reviews supports 5% lidocaine patches, 8% capsaicin patches, and botulinum toxin A injections as effective treatments in patients with peripheral neuropathic pain. In turn, single RCTs support evidence of doxepin, funapide, diclofenac, baclofen, clonidine, loperamide, and cannabidiol in neuropathic pain states. Topical administration of phenytoin, ambroxol, and prazosin is supported by observational clinical studies. For topical amitriptyline, menthol, and gabapentin, evidence comes from case reports and case series. For topical ketamine and baclofen, data supporting their effectiveness are provided by both single RCTs and case series. The discussed data from clinical studies and observations support the usefulness of topical treatments in neuropathic pain management. This review may help clinicians in making decisions regarding whether and which topical treatment may be a beneficial option, particularly in frail patients not tolerating systemic pharmacotherapy.

Understanding peripheral neuropathic pain in primary care: diagnosis and management.

To describe an approach that allows for a dedicated clinical assessment and accurate recognition of peripheral neuropathic pain in primary care and to provide an update on the available pharmacologic therapies MATERIALS AND METHODS: Medline was searched using the key word "neuropathic pain". Searches were refined for each pathophysiological mechanism, diagnosis and treatment by adding appropriate key words. The distinction between neuropathic and nociceptive pain is essential for an adequate treatment because these forms of pain differ in their underlying mechanisms and therefore in their response to different drugs. Chronic pain with neuropathic characteristics presents a significant challenge as it is often unresponsive to conventional analgesics. The correct diagnosis and early management of peripheral neuropathic pain not only improve health-related outcomes, but also yield significant cost benefit to society.

ALIAmides Update: Palmitoylethanolamide and Its Formulations on Management of Peripheral Neuropathic Pain.

Neuropathic pain results from lesions or diseases of the somatosensory nervous system and it remains largely difficult to treat. Peripheral neuropathic pain originates from injury to the peripheral nervous system (PNS) and manifests as a series of symptoms and complications, including allodynia and hyperalgesia. The aim of this review is to discuss a novel approach on neuropathic pain management, which is based on the knowledge of processes that underlie the development of peripheral neuropathic pain; in particular highlights the role of glia and mast cells in pain and neuroinflammation. ALIAmides (autacoid local injury antagonist amides) represent a group of endogenous bioactive lipids, including palmitoylethanolamide (PEA), which play a central role in numerous biological processes, including pain, inflammation, and lipid metabolism. These compounds are emerging thanks to their anti-inflammatory and anti-hyperalgesic effects, due to the down-regulation of activation of mast cells. Collectively, preclinical and clinical studies support the idea that ALIAmides merit further consideration as therapeutic approach for controlling inflammatory responses, pain, and related peripheral neuropathic pain.

Repetitive Magnetic Stimulation for the Management of Peripheral Neuropathic Pain: A Systematic Review

Repetitive magnetic stimulation (rMS) is a safe and well-tolerated intervention. Transcranial magnetic stimulation (TMS) is used for the treatment of depression and for the treatment and prevention of migraine. Over the last few years, several reports and randomised controlled studies of the use of rMS for the treatment of pain have been published. The aim of this systematic review was to identify the available literature regarding the use of rMS in the treatment of peripheral neuropathic pain. After a systematic Medline search we identified 12 papers eligible to be included in this review. The majority of the studies were on patients with phantom limb pain, followed by radiculopathy, plexopathy, post-traumatic pain and peripheral neuropathy. The treatment protocols vary significantly from study to study and, therefore, pooling the results together is currently difficult. However, rMS has a definite immediate effect in pain relief which, in the majority of studies, is maintained for a few weeks. rMS seems to be a promising intervention in the treatment of peripheral neuropathic pain. Further research is in the field is needed. Use of neuronavigation might increase the precision of stimulation and subsequently its effectiveness.

Patients' Global Impression of Change in the management of peripheral neuropathic pain: Clinical relevance and correlations in daily practice.

Patient-Reported Outcome (PRO) instruments have been developed to evaluate pain management in daily practice; the Patients' Global Impression of Change (PGIC) is particularly recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. The prospective non-interventional multicenter PRO-QURE study aimed at assessing correlations between PGIC and pain measurements and treatment effects in patients followed in French pain centres. Respectively, 495 and 379 patients with peripheral neuropathic pain initiating treatment with capsaicin 8% cutaneous patch(es) (female, 62.6%; mean age, 54.0±14.8years; post-surgical or traumatic pain, 52.7%; mean pain duration, 42.2±54.1months; DN4 score >4, 92.9%) completed the PGIC and several other PRO instruments before (baseline) and 3months (M3) after treatment application. At M3, improvement ("much improved" or "very much improved") was observed in 23.0% of patients, associated with decreases of -3.0±2.2, -2.5±2.4, and -23.1±19.7 in BPI pain intensity, BPI pain interference and NPSI total scores, respectively. The highest Spearman's rank correlation coefficients with PGIC were found for pain intensity (BPI: r=-0.479, p<0.001), satisfaction with current state (Patient Acceptable Symptomatic State: r=0.455, p<0.001), and treatment effectiveness (TSQM: r=0.431, p<0.001); correlation coefficients were lower for all NPSI scores, BPI pain interference score, HAD scores and EQ-5D-3L index. In daily clinical practice, significant improvement in peripheral neuropathic pain, as assessed by PGIC scores, significantly correlated with changes in well-established measures of pain intensity, pain interference with activities of daily living, mood and quality of life, confirming its clinical interest as PRO measure in real-world conditions. Clinically important improvement in peripheral neuropathic pain, as assessed by PGIC scores, significantly correlated with well-established measures of pain intensity, pain interference in daily life and treatment efficacy. This result, associated with the ease of administration and scoring, encourages the widespread use of the PGIC in daily practice.

Cupping with neural glides for the management of peripheral neuropathic plantar foot pain: a case study

ABSTRACTBackground/purpose: Plantar foot pain of neural origin is a challenging diagnosis to identify and treat. The purpose of this paper is to illustrate the novel way in which cupping was utilized in conjunction with neural glides to better diagnose and manage a patient who presented with symptoms of peripheral neuropathic plantar foot pain.Case description: A 65-year-old male presented to physical therapy with the diagnosis of plantar fasciitis by an orthopedic surgeon. The presentation included a diffuse area of pain toward the medial border of the foot with a peripheral neuropathic pain description. Cupping was used to identify pain in the saphenous nerve distribution and aided in resolving symptoms with the concomitant use of lower quarter neural glides.Outcome: At discharge and 1-year follow-up, the patient had a full resolution of symptoms and a return to prior level of function. Self-report outcomes included the numeric pain rating scale and the lower extremity functional scale.Discussion: This case is the first to describe the use of cupping combined with neural glides in the diagnosis and management of peripheral neuropathic pain from the saphenous nerve that was previously diagnosed as plantar fasciitis. The proposed mechanisms behind this treatment are also reviewed.Conclusion: In patients that present with symptoms of plantar fasciitis, testing neural glides combined with cupping may be warranted to confirm or refute the presence of a peripheral neuropathic pain source. Further studies are necessary to determine the mechanisms and further utility of the combined interventions in well controlled trials.Level of Evidence: Level IV

Effectiveness of the capsaicin 8% patch in the management of peripheral neuropathic pain in European clinical practice: the ASCEND study

BackgroundIn randomised studies, the capsaicin 8% patch has demonstrated effective pain relief in patients with peripheral neuropathic pain (PNP) arising from different aetiologies.MethodsASCEND was an open-label, non-interventional study of patients with non-diabetes-related PNP who received capsaicin 8% patch treatment, according to usual clinical practice, and were followed for ≤52 weeks. Co-primary endpoints were percentage change in the mean numeric pain rating scale (NPRS) ‘average daily pain’ score from baseline to the average of Weeks 2 and 8 following first treatment; and median time from first to second treatment. The primary analysis was intended to assess analgesic equivalence between post-herpetic neuralgia (PHN) and other PNP aetiologies. Health-related quality of life (HRQoL, using EQ-5D), Patient Global Impression of Change (PGIC) and tolerability were also assessed.ResultsFollowing first application, patients experienced a 26.6% (95% CI: 23.6, 29.62; n = 412) reduction in mean NPRS score from baseline to Weeks 2 and 8. Equivalence was demonstrated between PHN and the neuropathic back pain, post-operative and post-traumatic neuropathic pain and ‘other’ PNP aetiology subgroups. The median time from first to second treatment was 191 days (95% CI: 147, 235; n = 181). Forty-four percent of all patients were responders (≥30% reduction in NPRS score from baseline to Weeks 2 and 8) following first treatment, and 86.9% (n = 159/183) remained so at Week 12. A sustained pain response was observed until Week 52, with a 37.0% (95% CI: 31.3, 42.7; n = 176) reduction in mean NPRS score from baseline. Patients with the shortest duration of pain (0–0.72 years) experienced the highest pain response from baseline to Weeks 2 and 8. Mean EQ-5D index score improved by 0.199 utils (responders: 0.292 utils) from baseline to Week 2 and was maintained until Week 52. Most patients reported improvements in PGIC at Week 2 and at all follow-up assessments regardless of number of treatments received. Adverse events were primarily mild or moderate reversible application site reactions.ConclusionIn European clinical practice, the capsaicin 8% patch provided effective and sustained pain relief, substantially improved HRQoL, improved overall health status and was generally well tolerated in a heterogeneous PNP population.Trial registrationNCT01737294 Date of registration - October 22, 2012.

Prospective, Multicenter, Randomized, Double-Blinded, Partial Crossover Study to Assess the Safety and Efficacy of the Novel Neuromodulation System in the Treatment of Patients With Chronic Pain of Peripheral Nerve Origin.

Currently available central nervous system treatment strategies are often insufficient in management of peripheral neuropathic pain, prompting a resurgence of neuromodulation focused on peripheral pain. A new peripheral nerve stimulation device was investigated in a prospective, randomized, double blind, crossover study, looking specifically at efficacy and safety, with Food and Drug Administration oversight. Prospective, multicenter, randomized, double-blind, partial crossover study to assess safety and efficacy. After IRB approval, patients were enrolled, implanted, and then followed for three months to assess efficacy and one year for safety based on Food and Drug Administration guidance. One hundred forty-seven patients were consented and screened for the study. Thirty-five did not meet inclusion or exclusion criteria. Ninety-four patients were implanted and then randomized to the treatment (45) or the Control group (49). The primary efficacy endpoint, three months after randomization to treatment, demonstrated that patients receiving active stimulation achieved a statistically significantly higher response rate of 38% vs. the 10% rate found in the Control group (p = 0.0048). Improvement in pain was statistically significant between the randomized groups, with the Treatment group achieving a mean pain reduction of 27.2% from Baseline to Month 3 compared to a 2.3% reduction in the Control group (p < 0.0001). During the partial crossover period, patients again demonstrated statistically significant improvement in pain relief with active stimulation compared to baseline. Further, the Treatment group had significantly better improvement than the Control group in secondary measures including but not limited to quality of life and satisfaction. Safety, assessed throughout the trial and with follow-up to one year, demonstrated no serious adverse events related to the device. All device-related adverse events were minor and self-limiting. The novel peripheral nerve stimulation device is a safe and effective treatment strategy to address neuropathic pain of peripheral nerve origin.

Topical amitriptyline and ketamine for the treatment of neuropathic pain

A neuropathy is a disturbance of function or pathological change in nerves. In some cases, peripheral neuropathic pain may occur due to a lesion or disease of the peripheral somatosensory nervous system. Efficacy of different agents for peripheral neuropathic pain conditions is less than optimal. The administration of topical analgesics might be an option, due to the potential of reduced adverse effects and increased patient compliance. There is major interest in compounding topical analgesics for peripheral neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of peripheral neuropathic pain. Topical amitriptyline-ketamine combination (AK) is a promising agent for peripheral neuropathic pain conditions. Some studies have shown its efficacy in neuropathic pain conditions. However, this data was not uniformely obtained and its role remains still controversial. Efficacy may depend on many factors, including the choice of the vehicle, the concentration, the pain site, and specific diseases. More studies are necessary to support the use of AK in clinical practice.

Pregabalin versus gabapentin in the management of peripheral neuropathic pain associated with post-herpetic neuralgia and diabetic neuropathy: a cost effectiveness analysis for the Greek healthcare setting

BackgroundThe anticonvulsants pregabalin and gabapentin are both indicated for the treatment of peripheral neuropathic pain. The decision on which treatment provides the best alternative, should take into account all aspects of costs and outcomes associated with the two therapeutic options. The objective of this study was to examine the cost – effectiveness of the two agents in the management of patients with painful diabetic neuropathy or post – herpetic neuralgia, under the third party payer perspective in Greece.MethodsThe analysis was based on a dynamic simulation model which estimated and compared the costs and outcomes of pregabalin and gabapentin in a hypothetical cohort of 1,000 patients suffering from painful Diabetic Peripheral Neuropathy (DPN) or Post-Herpetic Neuralgia (PHN). In the model, each patient was randomly allocated an average pretreatment pain score, measured using an eleven-point visual analogue scale (0 – 10) and was “run through” the model, simulating their daily pain intensity and allowing for stochastic calculation of outcomes, taking into account medical interventions and the effectiveness of each treatment.ResultsPregabalin demonstrated a reduction in days with moderate to severe pain when compared to gabapentin. During the 12 weeks the pregabalin arm demonstrated a 0.1178 (SE 0.0002) QALY gain, which proved to be 0.0063 (SE 0.0003) higher than that in the gabapentin arm. The mean medication cost per patient was higher for the pregabalin arm when compared to the gabapentin arm (i.e. €134.40) over the 12 week treatment period. However, this higher cost was partially offset by the reduced direct medical costs (i.e. the cost of specialist visits, the cost of diagnostic tests and the other applied interventions). Comparing costs with respective outcomes, the ICERs for pregabalin versus gabapentin were €13 (95%CI: 8 – 18) per additional day with no or mild pain and €19,320 (95%CI: 11,743 – 26,755) per QALY gained.ConclusionsNeuropathic pain carries a great disease burden for patients and society and, is also, associated with a significant economic burden. The treatment of pain associated with DPN and PHN with pregabalin is a cost-effective intervention for the social security in Greece compared to gabapentin. Thus, these findings need to be taken into consideration in the decision – making process when considering which therapy to use for the treatment of neuropathic pain.

Cost Savings Associated With Early Initiation of Pregabalin in the Management of Peripheral Neuropathic Pain

Peripheral neuropathic pain (PNP) is associated with significant economic burden. Guidelines recommend the early adoption of appropriate pharmacological interventions. The aim of this study was to explore whether early initiation of pregabalin was associated with lower economic burden, than later initiation, in the management of refractory chronic PNP. A secondary analysis of a multicenter, observational cost-of-illness study was carried out in adults older than 18 years of age with refractory chronic PNP. Patients were pregabalin naive, with a poor response to previous analgesic therapy, defined as pain >40 in a 0 to 100 mm visual analog scale after, at least, 1 analgesic. The total costs, health care and indirect, assessed 12 weeks before the initiation of pregabalin were analyzed according to the time elapsed since diagnosis. One thousand one hundred thirty-nine outpatients, 59.3 (12.8) years old, 59.3% women, 2.0 (3.5) years with a diagnosis of PNP, fulfilled the criteria for analysis. Adjusted (pain intensity, sex, age, and body mass index) mean total costs 12 weeks before the baseline visit were significantly lower when pregabalin was initiated early (<6 mo; n=389) in comparison with later initiation; 6 to 12 months (n=328), or >12 months (n=422) after diagnosis; €2439 (2197; 2681) versus €3011 (2758; 3264) and €2945 (2717; 3173), respectively (P<0.01 in both cases). Lower health care costs and fewer lost-workday equivalents with early initiation of pregabalin were the main factors contributing to these findings. Early initiation of pregabalin treatment after diagnosis in patients with refractory chronic PNP may result in substantial cost savings from a societal perspective in daily practice in Spain.

Cost-utility of pregabalin as add-on to usual care versus usual care alone in the management of peripheral neuropathic pain in Belgium

Background and objectivess:The cost effectiveness of pregabalin as an add-on to the standard treatment of Belgian patients with post-herpetic neuralgia (PHN) had been demonstrated in a previously published Markov model. The purpose of this study was to update that model with more recent cost data and clinical evidence, and reevaluate the cost effectiveness from the payer’s perspective of add-on pregabalin in a wider set of NeP conditions.Methods:The model, featuring 4-week cycles and a 1-year time horizon, consisted in four possible health states: mild, moderate or severe pain and withdrawn from therapy. Three versions of the model were developed, using transition probabilities derived from pain scores reported in three placebo-controlled studies. The two treatment arms were ‘usual care’ or ‘usual care + pregabalin’. Resource use and utility data were obtained from a chart review and unit costs from recent published data. The final outcome of the model was the incremental cost per quality-adjusted life-year (QALY) gained when adding pregabalin to standard care.Results:Based on 1000 simulations, two versions of the model showed that pregabalin was dominant respectively in 94.8% and 67.2% of the simulations, while the incremental cost per QALY was below €32,000/QALY in respectively 99.1% and 94.6% of the simulations. The third version did not show cost effectiveness, despite an incremental cost of only €300 after 1 year. However, in the corresponding study, patients seemed less responsive to GABA analogs, since 55% of them had failed to respond to gabapentin before study inclusion.Limitations:The studies upon which the model is based have a short follow-up time as compared to the model horizon. The endpoints of two studies were only provided at the aggregated level and do not necessarily reflect the real practice.Conclusion:Based on this analysis, it can be concluded that from a Belgium payer perspective pregabalin offers a slight increase in quality of life in the studied populations as compared to standard care. Pregabalin is cost effective in the majority of cases except in one published clinical study, despite a low incremental cost per year (€300).

Managing foot disorders in patients with diabetes

In this article, issues relating to the management of foot disorders in patients with diabetes are discussed. These include the nature of foot ulceration, foot screening, and the management of peripheral neuropathic pain, neuropathic and ischaemic ulcers, infected foot ulcers, and Charcot foot.

Pharmacokinetic Analysis of Capsaicin After Topical Administration of a High-Concentration Capsaicin Patch to Patients With Peripheral Neuropathic Pain

Capsaicin, a pungent compound in chili peppers, is a highly selective agonist for the transient receptor potential vanilloid 1 receptor expressed in nociceptive sensory nerves. A high-concentration (640 microg/cm2) capsaicin patch, designated NGX-4010, is in clinical evaluation for the management of peripheral neuropathic pain. To determine systemic capsaicin exposure after single 60- or 90-minute NGX-4010 applications, plasma samples were collected from 173 patients with postherpetic neuralgia (PHN), painful human immunodeficiency virus-associated neuropathy (HIV-AN), and painful diabetic neuropathy (PDN). The percentages of patients with quantifiable levels of capsaicin at any time point were 31% for PHN (30 of 96), 7% for HIV-AN (3 of 44), and 3% for PDN (1 of 33). The maximum plasma concentration observed in any patient was 17.8 ng/mL. Due to the limited number of quantifiable levels, a population analysis was performed to characterize the pharmacokinetics (PK) of capsaicin. Plasma concentrations were fitted adequately using a 1-compartment model with first-order absorption and linear elimination. Capsaicin levels declined very rapidly, with a mean population elimination half-life of 1.64 hours. Mean area under the curve and C max values after a 60-minute application were 7.42 ng x h/mL and 1.86 ng/mL, respectively. Only a few correlations between calculated PK parameters and patient characteristics were observed. Duration and area of application of the patch were detected as significant covariates explaining the PK of capsaicin. Ninety-minute applications of NGX-4010 resulted in capsaicin area under the curve and Cmax values approximately 1.78- and 2.15-fold higher than those observed in patients treated for 60 minutes. Treatment on the feet (patients with HIV-AN and PDN) produced far lower systemic exposure than treatment on the trunk (patients with PHN). Finally, larger treatment areas were associated with statistically higher Vc/F values. The low systemic exposure and very rapid elimination half-life of capsaicin after NGX-4010 administration are unlikely to result in systemic effects and support the overall safety profile of this investigational cutaneous patch.

A COST-UTILITY ANALYSIS OF PREGABALIN IN THE MANAGEMENT OF PERIPHERAL NEUROPATHIC PAIN

OBJECTIVES: To assess the cost per QALY (quality-adjusted life years) of pregabalin in the management of peripheral neuropathic pain. METHODS: We compared pregabalin on top of “usual care” with “usual care” alone. In this study, usual care was defined as a mix of drug therapies, excluding anti-epileptic drugs (AEDs), because the latter represented only 9% of current use, and clinical evidence of pregabalin was demonstrated versus usual care without anti-epileptic drugs. A Markov model was developed to simulate the evolution of a patient cohort over 1 year, and applied cycles of 4 weeks. During each cycle, patients remained in 1 out of 4 possible states: severe, moderate or mild pain, and therapy withdrawal. The health care payers perspective was taken into account. Clinical data were obtained from a trial comparing usual care plus placebo to usual care plus pregabalin, at either 150, 300, or 300/600 mg/day (the latter depending on clearance of creatinin). Resulting effects on pain were transformed into transition-probabilities between different pain levels. Cost and SF36 utility data of pain levels were obtained from a 1-month observational study in 88 patients. RESULTS: Usual care resulted in a yearly cost of € 6,200 compared to € 5,984 for an all dose pregabalin-mix, meaning a cost saving of € 216 per patient. Utility increase was 0.01 for the pregabalin-mix (QALY 0.510 usual care; 0.520 pregabalin-mix). MonteCarlo analysis showed cost savings were not significant. However, the utility gain, albeit small, was statistically significant. CONCLUSIONS: Based on this analysis, it may be concluded, that in the considered patient population, at the specialist level, pregabalin is at least cost neutral to current usual care (without AEDs) and offers a slight but significant increase in quality of life.

Pregabalin in the management of central neuropathic pain

Central neuropathic pain is a painful condition, often severe, that occurs in a person who is already affected by an injury or disease of the brain or spinal cord. This dual insult is especially threatening to the quality of life of a person and their ability to perform even the most basic of tasks. Despite this high level of suffering there are relatively few trials investigating the management of central neuropathic pain. However, two randomised placebo-controlled studies have recently emerged demonstrating efficacy of pregabalin in reducing central neuropathic pain due to spinal cord injury and central poststroke pain. Pregabalin, an anticonvulsant, has been shown to be efficacious in the management of peripheral neuropathic pain of various causes and now may have a role to play in central neuropathic pain.