Treatment of painful polyneuropathies

The treatment of painful polpyneuropathies has begun to improve over the past several years. This is based on an evolving understanding of the pathogenesis related to the development of diabetic neuropathy and other diseases that may lead to peripheral nerve injury. Consensus on evaluation strategies for patients presenting with pain has furthered our ability to define neuropathic pain and accompanying signs and symptoms that may respond to particular therapeutic approaches. Recent therapeutic advances in medical management have demonstrated improved outcomes in pain relief. This, along with lower side effect-related issues, has led to improved compliance and patient satisfaction. The assessment and treatment of comorbid conditions, which include sleep, anxiety, and depression, have further advanced the management of painful polyneuropathies in patients. New antiepileptics, antidepressants, and topical therapies have contributed to improved patient outcomes.     

Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K

OBJECTIVE

To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy.

RESEARCH DESIGN AND METHODS

Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS).

RESULTS

Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS >8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7–2.4], P < 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR = 1.5 [1.4–1.6], P < 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P < 0.0001).

CONCLUSIONS

One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN.Neuropathy is one of the most common long-term complications of diabetes and is the main initiating factor for foot ulceration, Charcot neuroarthropathy, and lower-extremity amputation (1). However, the quality and even quantity of epidemiological data on symptomatic diabetic neuropathy remain poor due to inconsistent definitions, poor ascertainment, and a lack of population-based studies. Of three large, clinic-based studies from Europe, the prevalence of diabetic polyneuropathy varied from 23 to 29% (2–4). In the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) cohort of 2,368 type 2 diabetic patients with coronary artery disease, the prevalence of diabetic peripheral neuropathy was 51% (5). However, in all of these studies, although neuropathy symptoms were assessed as part of the diagnostic definition of diabetic neuropathy, the prevalence of painful diabetic neuropathy (PDN) per se was not established. In our large, community-based survey of 9,710 predominantly type 2 diabetic patients derived from general practice in northwest England, the prevalence of at least moderate neuropathic deficits as defined by a neuropathy disability score (NDS ≥6) was 22% and at least moderate neuropathy symptoms as defined by the neuropathy symptom score (NSS ≥5) was 34% (6).PDN is considered to be the cause of considerable morbidity and, under the auspices of the American Academy of Neurology, evidence-based guidelines have been published for the management of this difficult condition (7). However, there is a distinct paucity of robust, population-based epidemiological data on the prevalence and natural history of this condition, limited to a few small studies. Thus, in a small population-based study of 269 diabetic patients from Wales, whereas 64% reported pain, only 26% were confirmed to have PDN, but interestingly those with PDN had a significantly poorer quality of life compared with those with nonneuropathic pain (8). In a study of 350 diabetic patients from Liverpool, 13% of patients with PDN had never reported their symptoms to their treating physician and a further 39% had not received any treatment for PDN (9). In a recent study of 1,113 diabetic patients attending secondary care clinics across Turkey, whereas 62% had neuropathy based on abnormal nerve conduction and clinical examination, only 16% had neuropathic pain according to the Leeds Assessment of Neuropathic Symptoms and Signs score (10).The natural history of PDN remains unclear, although in a small longitudinal study, 77% of 56 diabetic patients with painful neuropathy were found to continue with nonabating pain after 5 years (11). Although it has been suggested that painful symptoms abate with progressive worsening of neuropathy, this has not been supported by a study that has demonstrated equal prevalence of painful symptoms in those with mild compared with more advanced neuropathy (12).Therefore there is a significant lack of large, population-based data defining the size of the neuropathic pain problem and attempting to provide some explanations toward pain etiology. We have had the unique opportunity to assess the following in a large, community-based diabetic population: 1) the prevalence of painful neuropathic symptoms; 2) the relationship between neuropathic symptoms and severity of clinical neuropathy; 3) the differences in neuropathic symptoms between patients with type 1 and type 2 diabetes; and 4) the role of sex and ethnicity.     

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial

Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect.     

Epidemiology and impact on quality of life of postherpetic neuralgia and painful diabetic neuropathy

OBJECTIVE: This article reviews the prevalence, risk factors, natural history, and impact on quality of life of painful diabetic neuropathy (PDN) and postherpetic neuralgia (PHN). DISCUSSION: Diabetes mellitus afflicts more than 14 million persons in the U.S. An estimated 20% to 24% of these persons experience PDN. Data on risk factors for PDN are limited, but duration of diabetes mellitus and poor glycemic control are probably important factors. Painful diabetic neuropathy may interfere with general activity, mood, mobility, work, social relations, sleep, leisure activities, and enjoyment of life. Herpes zoster strikes an estimated 800,000 persons each year in the U.S., most of whom are elderly or immunosuppressed. Using pain at 3 months after rash onset as a definition of PHN, between 25% and 50% of adults older than 50 years develop PHN, depending on early antiviral therapy for herpes zoster. Increasing age, greater pain and rash severity, greater degree of sensory impairment, and psychological distress are risk factors for PHN. Postherpetic neuralgia may cause fatigue, insomnia, depression, anxiety, interference with social roles and leisure activity, and impaired basic and instrumental activities of daily living. CONCLUSIONS: Both conditions are common complications of their underlying disorders and can profoundly diminish the quality of life of affected persons.     

Spinal cord stimulation in patients with painful diabetic neuropathy: A multicentre randomized clinical trial

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0–100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P < .001) and remained 67 (P = .97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life.     

Exercise-Induced Modulation of Pain in Adults With and Without Painful Diabetic Neuropathy

The purpose of this study was to examine exercise-induced pain modulation in diabetic adults with painful diabetic neuropathy (PDN) compared to diabetic adults without PDN. Eighteen adults diagnosed with type 2 diabetes with and without PDN (mean age of 49 years) completed 2 sessions. During the familiarization session, participants completed questionnaires, were familiarized with the pain testing protocols, and completed maximal isometric contractions. During the exercise session, experimental pain testing was completed before and following exercise consisting of 3 minutes of isometric exercise performed at 25% maximal voluntary contraction. Ratings of perceived exertion and muscle pain were assessed every 30 seconds during exercise. Results indicated that ratings of perceived exertion and muscle pain during exercise were significantly higher (P < .05) for diabetic adults with PDN versus diabetic adults without PDN. Diabetic adults with PDN did not experience changes in thermal pain ratings following exercise, whereas diabetic adults without PDN reported significantly lower pain ratings following exercise. It is concluded that diabetic adults with PDN experienced high levels of muscle pain during exercise and a lack of exercise-induced hypoalgesia following exercise, in comparison to diabetic adults without PDN, who experienced lower levels of muscle pain during exercise and a hypoalgesic response following exercise.PerspectiveVery little research has been conducted examining the impact of exercise on pain modulation in diabetic adults with PDN. This study provides support that adults with PDN exhibit exercise-induced endogenous pain modulatory system dysfunction.     

Diabetic neuropathies.

Diabetic neuropathy is a common complication of diabetes that may be associated both with considerable morbidity (painful polyneuropathy, neuropathic ulceration) and mortality (autonomic neuropathy). The epidemiology and natural history of diabetic neuropathy is clouded with uncertainty, largely caused by confusion in the definition and measurement of this disorder. We have reviewed various clinical manifestations associated with somatic and autonomic neuropathy, and we herein discuss current views related to the management of the various abnormalities. Although unproven, the best evidence suggests that near-normal control of blood glucose in the early years after diabetes onset may help delay the development of clinically significant nerve impairment. Intensive therapy to achieve normalization of blood glucose also may lead to reversibility of early diabetic neuropathy, but again, this is unproven. Our ability to manage successfully the many different manifestations of diabetic neuropathy depends ultimately on our success in uncovering the pathogenic processes underlying this disorder. The recent resurgence of interest in the vascular hypothesis, for example, has opened up new avenues of investigation for therapeutic intervention. Paralleling our increased understanding of the pathogenesis of diabetic neuropathy, refinements must be made in our ability to measure quantitatively the different types of defects that occur in this disorder. These tests must be validated and standardized to allow comparability between studies and more meaningful interpretation of study results.     

In vivo silencing of the CaV3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy

Earlier, we showed that streptozocin (STZ)-induced type 1 diabetes in rats leads to the development of painful peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia and mechanical allodynia accompanied by significant enhancement of T-type calcium currents (T-currents) and cellular excitability in medium-sized dorsal root ganglion (DRG) neurons. Here, we studied the in vivo and in vitro effects of gene-silencing therapy specific for the Ca_V3.2 isoform of T-channels, on thermal and mechanical hypersensitivities, and T-current expression in small- and medium-sized DRG neurons of STZ-treated rats. We found that silencing of the T-channel Ca_V3.2 isoform using antisense oligonucleotides, had a profound and selective anti-hyperalgesic effect in diabetic rats and is accompanied by significant down-regulation of T-currents in DRG neurons. Anti-hyperalgesic effects of Ca_V3.2 antisense oligonucleotides in diabetic rats were similar in models of rapid and slow onset of hyperglycemia following intravenous and intraperitoneal injections of STZ, respectively. Furthermore, treatments of diabetic rats with daily insulin injections reversed T-current alterations in DRG neurons in parallel with reversal of thermal and mechanical hypersensitivities in vivo. This confirms that Ca_V3.2 T-channels, important signal amplifiers in peripheral sensory neurons, may contribute to the cellular hyperexcitability that ultimately leads to the development of painful PDN.     

Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage ‘enriched enrollment’ design

Because a variety of mechanisms may generate pain in neuropathic pain syndromes, conventional clinical trial methods may fail to identify some potentially useful drugs; a drug affecting just a single mechanism may work in too few patients to yield a statistically significant result for the trial. To test a previous clinical observation that approximately one-quarter of patients with painful diabetic neuropathy appear responsive to clonidine, we conducted a formal clinical trial of transdermal clonidine in painful diabetic neuropathy patients using a 2-stage enriched enrollment design. In the first stage (study I), 41 patients with painful diabetic neuropathy completed a randomized, 3-period crossover comparison of transdermal clonidine (titrated from 0.1 to 0.3 mg/day) to placebo patches. Twelve apparent responders from study I were entered into the ‘enriched enrollment’ second stage (study II), consisting of an additional 4 double-blind, randomized, 1-week treatment periods with transdermal clonidine and placebo. Study I showed that in the overall group of 41 patients, pain intensity differed little during clonidine and placebo treatment. In study II, however, the 12 apparent responders from study I had 20% less pain with clonidine than placebo (95% confidence interval (CI): 4–35% pain reduction; P = 0.015), confirming that their pain was responsive to clonidine. None of the 3 consistent clonidine responders who were tested with the -adrenergic blocker phentolamine had relief of pain, suggesting that clonidine's pain relief is not mediated by a decrease in sympathetic outflow. A post-hoc analysis of many variables suggested that patients who described their pain as sharp and shooting may have a greater likelihood of responding to clonidine. The results of this study support the hypothesis that there is a subset of patients with painful diabetic neuropathy who benefit from systemic clonidine administration and illustrate the value of an enriched enrollment technique in analgesic trials.     

A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial

OBJECTIVE

To compare the efficacy and safety of duloxetine and amitriptyline in painful diabetic neuropathy (PDN).

RESEARCH DESIGN AND METHODS

In this randomized, double-blind, cross-over, active-control trial, 58 patients received amitriptyline and duloxetine orally once daily at bedtime, each for 6 weeks with optional dose uptitration fortnightly. Single-blinded placebo washout was given for 2 weeks between the two treatments and a single-blinded placebo run-out phase of 4 weeks was given at the end of the treatment period. Pain relief was measured by the patient’s global assessment of efficacy, using a visual analog scale (0–100) as a primary end point, and overall improvement and adverse events were assessed as secondary outcome measures. Median pain score reductions of >50%, 25–50%, and <25% were considered good, moderate, and mild responses, respectively.

RESULTS

There was a significant improvement in pain with both treatments compared with their baseline values (P < 0.001 for both). Good, moderate, and mild pain relief was achieved in 55, 24, and 15% of patients, respectively, on amitriptyline and 59, 21, and 9% of patients, respectively, on duloxetine. There were no significant differences in various other outcome measures between the groups. Of the reported adverse events, dry mouth was significantly more common with amitriptyline than duloxetine (55 vs. 24%; P < 0.01). Although, numerically, more patients preferred duloxetine, overall this was not statistically significant (48 vs. 36%; P = 0.18).

CONCLUSIONS

Both duloxetine and amitriptyline demonstrated similar efficacy in PDN. A large, multicentric clinical trial in other populations could possibly demonstrate the superiority of either drug.The management of painful diabetic neuropathy (PDN) includes intensive glycemic control and drugs for pain relief. The American Diabetes Association recommends amitriptyline, a tricyclic antidepressant, as the first choice; however, titration to higher doses is limited by its anticholinergic adverse effects (1). The selective serotonin norepinephrine reuptake inhibitor, duloxetine, is approved by the Food and Drug Administration for the treatment of PDN. It attenuates persistent pain mechanisms, including the central sensitization and hyperexcitability of the spinal and supraspinal pain-transmitting pathways. Duloxetine has been evaluated in placebo-controlled trials for a variety of chronic pain, including PDN (2–6). It not only relieves pain but also improves functionality and quality of life in patients with PDN. An extensive search of literature did not reveal any head-to-head comparison of duloxetine with amitriptyline, an established first-line therapy for PDN (1). Thus, the current study was planned to compare the efficacy and safety of duloxetine with amitriptyline in PDN.     

18. Painful Diabetic Polyneuropathy

In the industrialized world, polyneuropathy induced by diabetes mellitus (DM) is one of the most prevalent forms of neuropathy. Diabetic neuropathy can result from a direct toxic effect of glucose on nerve cells. Additionally, the damage of the nerve structures (central and peripheral) is accompanied by a microvascular dysfunction, which damages the vasa nervorum. More than 80% of the patients with DM‐induced polyneuropathy have a distal and symmetric presentation. The initial symptoms are: signs of diminished sensation, burning feet, which may occur particularly during the night and worsen when touched, and tingling sensation in the feet. Attacks of shooting pain may also occur. Proper control of DM is mandatory. Based on the recently published National Institute for Health and Clinical Excellence guidelines, treatment of painful diabetic neuropathy should start with duloxetine or amitriptyline if duloxetine is contraindicated. If pain relief is inadequate, monotherapy with amitriptyline or pregabalin, or combination therapy with amitriptyline and pregabalin should be considered. If pain relief is still insufficient, tramadol instead of or in combination with a second‐line agent should be considered. In patients who are unable to take oral medication, topical lidocaine can be considered for localized pain. There are currently four studies showing that spinal cord stimulation can potentially provide pain alleviation for the longer term in patients with painful diabetic polyneuropathy. Complications are mainly implant related, though infections also occur. The available evidence (2 C+) justifies spinal cord stimulation to be considered, preferably study related.     

AIDS and AIDS-treatment neuropathies

AIDS and AIDS-treatment neuropathies are common in individuals infected with HIV. As patients live longer due to improved antiretroviral therapies, the impact of painful neuropathy on patients’ lives may increase. Several antiretroviral medications are known to cause toxic neuropathy in patients with AIDS, but this may be outweighed by the beneficial effects of viral suppression. Current theories on the pathogenesis of AIDS neuropathies include mitochondrial toxicity secondary to γ-DNA polymerase inhibition and subsequent abnormal mitochondrial DNA synthesis. Treatment of AIDS neuropathies is directed toward relief of symptoms; however, new evidence suggests that aggressive antiretroviral therapy may also be effective.     

Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up.

OBJECTIVE--We conducted an 8-wk controlled study with topical 0.075% capsaicin in subjects with chronic severe painful diabetic neuropathy who were unresponsive or intolerant to conventional therapy. Capsaicin is an alkaloid found in capsicum peppers and produces desensitization to noxious thermal, chemical, and mechanical stimuli when applied topically. RESEARCH DESIGN AND METHODS--In 22 randomly assigned subjects, either capsaicin or vehicle cream was applied to painful areas 4 times/day. Pain measurements were recorded at baseline and at 2-wk intervals for 8 wk. RESULTS--Capsaicin treatment was more beneficial than vehicle treatment in the overall clinical improvement of pain status, as measured by physician's global evaluation (P = 0.038) and by a categorical pain severity scale (P = 0.057). Decrease in mean pain intensity by a visual analogue scale was 16% in capsaicin-treated and 4.1% in vehicle-treated subjects. Mean pain relief on visual analogue scale was 44.6 and 23.2%, respectively. In a follow-up open-label study, approximately 50% of subjects reported improved pain control or were cured, and 25% each were unchanged or worse. A burning sensation at the application site was noted by some subjects but both its magnitude and duration decreased with time. CONCLUSIONS-- Results from this preliminary study suggest that topical 0.075% capsaicin may be of value in subjects with diabetic neuropathy and intractable pain.     

循证护理、自我效能在糖尿病痛性神经病变中的联合应用

目的 探讨循证护理、自我效能在糖尿病痛性神经病变患者护理中联合应用的效果.方法 将84例糖尿病痛性神经病变患者随机分为两组.护理干预组应用循证护理的理论,针对研究对象的具体情况,提出循证问题,寻求最佳护理行为并实施干预,同时联合自我效能,为期1个月;对照组进行常规护理.结果 护理干预后干预组疼痛分值有明显下降,各项自我效能分值和护理满意度明显升高,同对照组比较有显著性差异(P＜0.05).结论 通过循证护理和自我效能的联合干预,能有效缓解糖尿病痛性神经病变患者的疼痛症状,减轻患者的痛苦,提高护理满意度.     

Dextromethorphan and diabetic neuropathy

OBJECTIVE: To review the use of dextromethorphan for the treatment of painful diabetic neuropathy. DATA SOURCES: MEDLINE and EMBASE searches for studies using dextromethorphan to manage diabetic neuropathy were conducted from 1966 to 1999 and 1980 to 1999, respectively. DATA SYNTHESIS: Peripheral neuropathy is a common manifestation of diabetic patients. Many classes of medications have been investigated to treat this condition, including N-methyl-D-aspartate inhibitors. A review of studies using dextromethorphan to manage diabetic neuropathy was performed. CONCLUSIONS: There are insufficient safety and efficacy data to justify the use of dextromethorphan for treating painful diabetic neuropathy. Further clinical trials are needed.     

Acute painful neuropathy restricted to the abdomen following rapid glycaemic control in type 2 diabetes

A 46-year-old Japanese man with type 2 diabetes mellitus, whose only diabetic complication was simple retinopathy, developed acute painful neuropathy. This presented as paresthesia and hyperesthesia restricted to the abdomen. The patient's haemoglobin A(1c) had dropped from 12% to 7.5% within 5 months, following a rapid improvement in glycaemic control. On investigation, there were no indications of disease in the intraabdominal area. Nerve conduction studies were consistent with mild sensorimotor peripheral and autonomic neuropathy. The patient required medication (mexiletine, sulpiride and imipramine hydrochloride) to control the pain. Four months after presentation, the symptoms showed a dramatic improvement and the treatment for pain relief was discontinued without any recurrence of paresthesia or hyperesthesia in the patient's abdomen. This was a very unusual case of diabetic post-treatment painful neuropathy in which the prominent features were severe pain, paresthesia and hyperesthesia restricted to the abdomen.     

Treatment of diabetic neuropathy and neuropathic pain: how far have we come?

At least one of four diabetic patients is affected by distal symmetric polyneuropathy, which represents a major health problem, since it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity, increased mortality, and impaired quality of life. Treatment is based on four cornerstones: 1) causal treatment aimed at (near)-normoglycemia, 2) treatment based on pathogenetic mechanisms, 3) symptomatic treatment, and 4) avoidance of risk factors and complications. Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. From the clinical point of view, it is important to note that, based on these pathogenetic mechanisms, therapeutic approaches could be derived, some of which are currently being evaluated in clinical trials. Among these agents, only alpha-lipoic acid is available for treatment in several countries and epalrestat in Japan. Although several novel analgesic drugs such as duloxetine and pregabalin have recently been introduced into clinical practice, the pharmacologic treatment of chronic painful diabetic neuropathy remains a challenge for the physician. Individual tolerability remains a major aspect in any treatment decision. Epidemiological data indicate that not only increased alcohol consumption but also the traditional cardiovascular risk factors such as hypertension, smoking, and cholesterol play a role in development and progression of diabetic neuropathy and hence need to be prevented or treated.     

A Randomized,Controlled Trial of Oxycodone Versus Placebo in Patients With PostHerpetic Neuralgia and Painful Diabetic Neuropathy Treated With Pregabalin

The aim of this randomized double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of pregabalin in combination with oxycodone or placebo, in patients with either postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN). After a 7-day washout period, 62 patients were randomized to receive either oxycodone mixture 10 mg/day or placebo mixture for 1 week. Patients were then started on open-label pregabalin (75, 150, 300 and 600 mg/day) according to a forced titration dosing regimen, while continuing the same dosage of oxycodone or placebo for 4 weeks. The primary efficacy measure was a decrease in the pain-intensity score of at least 2cm and a pain score <4cm measured using a 10-cm visual analogue scale (VAS) following pregabalin dosage escalation and treatment for 4 weeks. Secondary efficacy measures included sleep interference and the Neuropathic Pain Scale. There were similar levels of overall efficacy between pregabalin/oxycodone and pregabalin/placebo groups in relieving PHN and PDN related pain.PerspectivePeripheral neuropathic pain presents commonly in clinical practice, and 2 of its most prevalent types are PHN and PDN. Currently available treatments provide some degree of pain relief in ～40-60% of patients, leaving the remainder with unremitting pain. Although this study supports the effectiveness of pregabalin in the treatment of PHN or PDN, it also shows that the addition of a low dose of oxycodone at 10mg/day does not enhance the pain-relieving effects of pregabalin.     

A Randomized Controlled Pilot Study of a Cognitive-Behavioral Therapy Approach for Painful Diabetic Peripheral Neuropathy

The purpose of the present pilot study was to assess the efficacy of cognitive-behavioral therapy (CBT) for painful diabetic peripheral neuropathy. This was a randomized, treatment as usual (TAU), controlled, nonblinded intervention pilot study with a 4-month follow-up conducted in a VA medical center. It was hypothesized that participants who received CBT, as compared to those who received TAU, would report significant decreases on self-report measures of pain severity, interference, and depressive symptoms from pretreatment to 4-month follow-up. Participants meeting inclusion criteria were randomly assigned to 1 of the study conditions. Of the 20 eligible participants, 12 were randomized to CBT and 8 were randomized to TAU. Participants randomized to CBT showed significant decreases on measures of pain severity (B = ?.54) and pain interference (B = ?.77) from pretreatment to 4-month follow-up. There were no significant changes in the TAU participants' scores on measures of pain severity (B = .00) or pain interference (B = ?.09). Neither CBT nor TAU participants showed significant changes in their levels of depressive symptoms from pretreatment to 4-month follow-up. CBT may be an effective treatment approach for reducing pain severity and interference associated with painful diabetic peripheral neuropathy.PerspectiveThe results of this study suggest that engaging patients in CBT for painful diabetic peripheral neuropathy may provide them the skills to become more active and experience less pain.