Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs.

BACKGROUND AND PURPOSE: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. METHODS: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. RESULTS: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. CONCLUSIONS: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

Randomized trial of facilitated subcutaneous immunoglobulin in multifocal motor neuropathy.

BACKGROUND AND PURPOSE: To optimize subcutaneous therapy with immunoglobulins, large volume infusion of immunoglobulin G facilitated by pretreatment with hyaluronidase (fSCIG) was compared to conventional infusion of multiple small dosages (cSCIG) in 20 patients with multifocal motor neuropathy. METHODS: A randomized, non-inferiority and observer-blinded cross-over design was applied with a treatment period of 24 weeks for each therapy. RESULTS: In 18 patients fSCIG was feasible, two patients leaving the study due to side-effects. The primary study variable, isometric strength, was unchanged, being 100.8% [95% confidence interval (CI) 94.8%-107.1%) in fSCIG and 105.9% (95% CI 99.8%-112.0%) in cSCIG. Secondary end-points of disability, functions, impairments and quality of life showed no differences between the two treatments. Mild and short-lasting generalized side-effects were similar in the two groups, whereas the relative frequency of localized side-effects at the injection site was increased after fSCIG [0.63 (95% CI 0.23-1.00) vs. 0.09 (95% CI 0.00-0.22), P = 0.005]. The preference of the patients favoured fSCIG for two out of five visual analogue scale scores as well as the total mean score of all preferences (P = 0.03). CONCLUSIONS: Facilitated SCIG seems effective, feasible and safe. In addition, it is preferred by patients but is accompanied by a higher frequency of short-lasting localized side-effects.

Impact of etiology and duration of pain on pharmacological treatment effects in painful polyneuropathy.

BACKGROUND: The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for. METHODS: We analysed data from four published, randomized, controlled trials of drugs in painful polyneuropathy to see if diabetic etiology and duration of neuropathic pain had an impact on drug efficacy. The studies had a cross-over design, and had nearly similar outcome recordings as well as a thorough baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed. RESULTS: Diabetes as etiology of polyneuropathy had no impact on the effect of antidepressants (imipramine, venlafaxine, escitalopram), but there was a significant interaction with treatment effect on anticonvulsants with better effects in diabetics (0.86 NRS points, p = 0.021) with most pronounced interaction for oxcarbazepine (1.47 NRS points, p = 0.032). There was an interaction between duration of neuropathic pain and treatment with antidepressants with better effect with duration less than 3 years (0.62 NRS points, p = 0.036), whereas anticonvulsants tended to work best with duration of pain for more than 3 years. CONCLUSION: Despite the small sample size and limited number of drugs included this study suggests that diabetic etiology of polyneuropathy may impact on the efficacy of anticonvulsants, and duration of neuropathic pain may impact on the efficacy of antidepressants. SIGNIFICANCE: This study found that duration of pain appears to have an impact on the effect of antidepressants in neuropathic pain and that diabetes as etiology for painful polyneuropathy appears to influence pain relief obtained with anticonvulsants.

Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy: randomized controlled trial study.

BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment-naive patients with CIDP. METHODS: Twenty patients fulfilling the clinical and electrophysiological criteria for CIDP were included and treated with either SCIG (0.4 g/kg/week) for 5 weeks or intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days. After 10 weeks, patients were switched to the opposite treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG. Disability improved during SCIG treatment only. Muscle strength determined by manual muscle testing improved after 5 and 10 weeks during SCIG but only after 5 weeks during IVIG. The remaining parameters improved equally during both treatments. Plasma immunoglobulin G levels at baseline and improvement of cIKS were related. CONCLUSION: In treatment-naive patients with CIDP, short-lasting SCIG and IVIG therapy improve motor performance to a similar degree, but with earlier maximal improvement following IVIG than SCIG treatment.

Subcutaneous immunoglobulin preserves muscle strength in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year in an open-label follow-up study. METHODS: Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were evaluated after 3, 6 and 12 months. Primary end-points were changes in muscle strength evaluated by isokinetic dynamometry in four affected muscle groups and a composite score of muscle performance and function tests, including Medical Research Council (MRC) score, grip strength, 40-m walking test (40-MWT) and nine-hole peg test (9-HPT). Secondary end-points were changes of each of the listed parameters at each time point as well as an overall disability sum score (ODSS). RESULTS: The dose of SCIG was significantly unaltered during the follow-up period. Overall the isokinetic dynamometry value increased by 7.2% (P = 0.033) and after 3, 6 and 12 months by 5.7%, 8.2% and 6.8% (ns). The overall composite score at all time intervals and for each interval remained unchanged. Amongst the secondary parameters the MRC score increased significantly by 1.7% (P = 0.007), whereas grip strength, 40-MWT, 9-HPT and ODSS remained unchanged. CONCLUSION: SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long-term treatment of CIDP patients.

Characterization and diagnostic evaluation of chronic polyneuropathies induced by oxaliplatin and docetaxel comparing skin biopsy to quantitative sensory testing and nerve conduction studies.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy negatively affects the quality of life for many patients treated with oxaliplatin or docetaxel for gastrointestinal cancer or breast cancer. Symptoms can persist long after treatment and often include neuropathic pain. Our objective was to characterize the neuropathies with regard to symptoms, neurological signs and objective evidence of damage to the structure and function of the peripheral nerves. Furthermore, the diagnostic values of skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS) were compared. METHODS: Patients complaining of neuropathy symptoms at least 3 months after completion of treatment with oxaliplatin (n = 20) or docetaxel (n = 20) were recruited from the Department of Oncology or using hospital records. Neuropathy scores were determined along with the intraepidermal nerve fibre density in skin biopsies from the proximal and distal parts of the leg, QST and NCS. RESULTS: Clinically only sensory functions were affected. In general, neuropathy scores were higher in the oxaliplatin-treated group. Both sensory and motor fibres were affected in the NCS, showing predominantly signs of axonal damage. Mechanical detection threshold was most often affected in the QST. NCS, QTS and skin biopsy were abnormal in 11, 13 and 17 and 7, 11 and 15 of the oxaliplatin-treated patients and docetaxel-treated patients, respectively. CONCLUSIONS: Chemotherapy-induced peripheral neuropathy after oxaliplatin or docetaxel treatment is a clinically sensory, axonal neuropathy affecting only small nerve fibres in some patients. NCS are often normal, whereas QST and skin biopsy have a higher diagnostic sensitivity.

Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18-80 years, were randomized either to SCIG at a dose corresponding to their pre-study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial as well as 2 weeks before (-2, 0, 10, 12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was measured. Also, an Overall Disability Sum Score (ODSS), 40-m-walking test (40-MWT), nine-hole-peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. RESULTS: SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group there was an increase of isokinetic muscle strength of 5.5 ± 9.5% (P < 0.05) as compared with a decline of 14.4 ± 20.3% (P < 0.05) in the placebo group; the difference between the two groups being significant (P < 0.01). ODSS, NIS, MRC, grip strength and 40-MWT improved following SCIG versus saline. CONCLUSIONS: SCIG treatment in CIDP is feasible, safe and effective, and seems an attractive alternative to IVIG.

Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy.

GRT9906 is an investigational novel compound with µ-opioid receptor agonism and inhibition of noradrenalin/serotonin re-uptake. In this randomized, double-blind, placebo-controlled, three-way cross-over trial in painful polyneuropathy, the efficacy and safety of GRT9906 was assessed and compared with tramadol. During 4-week treatment periods, daily oral doses of either GRT9906 120-240 mg, or placebo, or tramadol 200-400 mg were given. These were separated by 1-week washout periods. The primary endpoint was the average pain intensity (average of daily current pain intensity over the last 3 days of each treatment period rated on a 0 to 10-point numeric rating scale). One hundred seventeen patients were enrolled and 64 were randomized to one of six treatment sequences. Forty-seven patients qualified for the per protocol analysis. GRT9906 reduced average pain intensity by 2.1 points compared with a reduction of 0.6 points on placebo (p < 0.0001) and 2.4 points on tramadol. GRT9906 also improved scores on the sleep problem scale and the neuropathic pain symptom inventory and scored better than placebo on the patient global impression of change. Numbers needed to treat to obtain one patient with more than 50% pain relief was 3.9 (95% CI 2.4-11.5) for both GRT9906 and tramadol. The most frequently reported adverse events were nausea, fatigue, constipation and sleep disorder for GRT9906 and tramadol. Four patients dropped out due to adverse events during both GRT9906 and tramadol treatment and two dropped out during placebo treatment. In conclusion, in painful polyneuropathy, GRT9906 demonstrated analgesic efficacy with a magnitude of effect comparable with tramadol and was well tolerated.

A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis.

Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well as pain intensity of more than 4 on a 0 to 10-point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Eighty-nine patients were screened for participation and 30 patients entered the study. Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.

Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management.

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co-morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti-depressants, the selective serotonin and noradrenaline re-uptake inhibitors, anti-convulsants, opiates, membrane stabilizers, the anti-oxidant alpha-lipoic acid and topical agents including capsaicin. Current first-line therapies for painful DPN include tricyclic anti-depressants, the serotonin and noradrenaline re-uptake inhibitor duloxetine and the anti-convulsants pregabalin and gabapentin. When prescribing any of these agents, other co-morbidities and costs must be taken into account. Second-line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone-controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long-term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non-pharmacological approaches.

Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia.

BACKGROUND: Oxycodone is a semi-synthetic opioid with a mu-receptor agonist-mediated effect in several pain conditions, including post-operative pain. Oxycodone is metabolized to its active metabolite oxymorphone by O-demethylation via the polymorphic CYP2D6. The aim of this study was to investigate whether CYP2D6 poor metabolizers (PMs) yield the same analgesia post-operatively from intravenous oxycodone as extensive metabolizers (EMs). METHODS: Two hundred and seventy patients undergoing primarily thyroid surgery or hysterectomy were included and followed for 24 h post-operatively. The CYP2D6 genotype was blinded until study procedures had been completed for all patients. All patients received intravenous oxycodone as pain treatment for 24 h post-operatively and morphine 5 mg was used as escape medication. A responder was characterized as a patient without the need for escape medication and a positive evaluation in a questionnaire 24 h post-operatively. RESULTS: Twenty-four patients were PM (8.9%) and 246 were EM (91.1%). One PM (4.17%, CI=0.1-21.1) was a non-responder and 42 EM (17.07%, CI=12.6-22.4) were non-responders. The non-responder rate did not differ between the two genotypes (P=0.14). There was no difference in the total consumption of oxycodone between the two genotypes (EM=14.7 mg, CI=13.0-16.4 and PM=13.0 mg, CI=8.9-17.0, P=0.42). The mean oxymorphone/oxycodone ratios were 0.0031 and 0.00081 in the EMs and PMs, respectively (P<0.0001). CONCLUSION: This study showed for the first time in patients that the oxymorphone formation depends on CYP2D6, but we found no difference in the post-operative analgesic effect of intravenous oxycodone between the two CYP2D6 genotypes.

Escitalopram is a weak inhibitor of the CYP2D6-catalyzed O-demethylation of (+)-tramadol but does not reduce the hypoalgesic effect in experimental pain.

Tramadol is O-demethylated to the active metabolite (+)-O-desmethyltramadol ((+)-M1) via CYP2D6, an enzyme that is weakly inhibited by escitalopram. We investigated the possibility of a pharmacokinetic (PK) and pharmacodynamic (PD) effect of escitalopram on tramadol metabolism. Fifteen healthy subjects completed this randomized, double-blind, three-phase, crossover trial. Combinations of escitalopram 20 mg/day or placebo together with tramadol 150 mg or placebo were used. Blood samples for pharmacokinetics were drawn at 0-24 h after medication. The analgesic effect of (+)-M was assessed by the cold pressor test (CPT) (area under effect curve, 1-12 h after medication (AUEC(1-12))). The median area under plasma concentration-time curve extrapolated to infinity (AUC(0-infinity)) of (+)-M1 was 2.75 micromol/l.h after placebo pretreatment compared with 1.95 micromol/l.h after escitalopram (P = 0.0027). The mean AUEC(1-12) of CPT were 4,140 and 4,388 cm.s after placebo and escitalopram, respectively (P = 0.71). Although escitalopram is a weak inhibitor of CYP2D6, it does not impair the analgesic effect of tramadol.

Levetiracetam in spinal cord injury pain: a randomized controlled trial.

STUDY DESIGN: A randomized, double-blind, placebo-controlled, crossover, multicenter trial. A 1-week baseline period was followed by two treatment periods of 5 weeks duration with levetiracetam increased from 500 mg b.i.d. to a maximum of 1500 mg b.i.d. separated by a 1-week washout period. OBJECTIVES: The objective of the study was primarily to evaluate the efficacy of the anticonvulsant levetiracetam in patients with spinal cord injury (SCI) at- and below-level pain and secondarily to evaluate the effect on spasm severity. SETTING: Outpatients at two spinal cord units and a pain center. METHODS: Patients were allowed to continue their usual pain treatment at a constant dose. The primary outcome measure was the change in median daily pain score (on a 0-10 point numeric rating scale) from 1-week baseline period to the last week of each treatment period. Secondary outcome measures included pain relief of at- and below-level pain, allodynia, spasms and spasticity. RESULTS: A total of 36 patients with SCI at- and or below-level pain were enrolled. Of these, 24 patients completed the trial. We found no effect of levetiracetam on the primary (P=0.46) or any of the secondary outcome measures. Only two patients continued levetiracetam treatment following the trial, and one patient was still in levetiracetam treatment at the 6-month follow-up. Levetiracetam was generally well tolerated with no serious adverse events. CONCLUSIONS: Levetiracetam does not relieve neuropathic pain or spasm severity following spinal cord injury.

Impact of CYP2C19 phenotypes on escitalopram metabolism and an evaluation of pupillometry as a serotonergic biomarker.

PURPOSE: To investigate the impact of cytochrome P450 2C19 (CYP2C19) phenotypes on escitalopram metabolism and to evaluate pupillometry as a serotonergic biomarker. METHODS: This was a double-blind, crossover design study with single and multiple doses of 10 mg escitalopram and placebo in panels of CYP2C19 extensive (EM) and poor metabolisers (PM). Pupillometry was measured by a NeurOptics Pupillometer-PLR. RESULTS: Five PM and eight EM completed the study. The CYP2C19 phenotype significantly affected the metabolism of escitalopram. The area under the time-plasma concentration curve (AUC(0-24)) was 1.8-fold higher in PM than in EM after both single and multiple doses. Escitalopram treatment did not affect the maximum pupil size, but it did statistically significantly decrease the relative amplitude of the pupil light reflex compared to the placebo; this effect was equal in both phenotype groups. CONCLUSIONS: The CYP2C19 polymorphism affects escitalopram metabolism, but the difference does not justify dose adjustment. The puzzling results from pupillometry can be due to interplay between a central and a local serotonergic effect. Based on these results, pupillometry can not be recommended as a serotonergic biomarker.

Sensory function and pain in a population of patients treated for breast cancer.

BACKGROUND: Chronic pain is often reported after surgery for breast cancer. This study examined pain and sensory abnormalities in women following breast cancer surgery. METHODS: Sensory tests were carried out on the operated and contra-lateral side in 55 women with chronic pain after breast cancer treatment and in a reference group of 27 pain-free women, who had also undergone treatment for breast cancer. Testing included a numeric rating score of spontaneous pain, detection and pain threshold to thermal and dynamic mechanical stimuli and temporal summation to repetitive pinprick stimulation. The neuropathic pain symptom inventory was applied for participants with chronic pain. RESULTS: The mean age was 58.6 years for the pain patients and 60.6 years for the pain-free patients. Thermal thresholds were significantly higher on the operated side than on the contra-lateral side in both groups and side difference in warmth detection threshold was significantly higher in the pain group than in the pain-free group (mean 3.8 degrees C vs. 1.1 degrees C, P=0.01). The frequency of cold allodynia was higher in participants with pain than in pain-free participants (15/53 vs. 1/25, P=0.01), and the frequency of temporal summation evoked by repetitive pinprick was higher in participants with pain than in pain-free participants (23/53 vs. 2/25, P=0.0009). The frequency of dynamic mechanical allodynia did not differ significantly between the two groups. CONCLUSION: These findings suggest that chronic pain after surgery for breast cancer is associated with sensory hyperexcitability and is a neuropathic pain condition.

Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial.

BACKGROUND AND PURPOSE: For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better quality of life. METHODS: In a randomized single-blinded cross-over study, nine IVIG responsive patients were allocated to receive either SCIG or IVIG for a period equivalent to three IVIG treatment intervals and, subsequently, crossed over to the other treatment. Primary end-points were (i) dynamometric strength of affected muscles and (ii) the SF-36 quality of life questionnaire. RESULTS: The two treatments were equally effective, the mean change in muscle strength after SCIG being 3.6% (95% CI -3.6% to 10.9%) vs. 4.3% (-1.3% to 10.0%) after IVIG (P = 0.86). One patient had sustained erythema and oedema at the injection sites for a few weeks. All other adverse effects during SCIG were mild and transient. No differences between treatments of health-related quality of life occurred. CONCLUSION: In MMN, short-term subcutaneous infusion of immunoglobulin is feasible, safe and as effective as intravenous infusion. Subcutaneous administration is an alternative option that adds flexibility to the treatment schedule.

The postmastectomy pain syndrome: an epidemiological study on the prevalence of chronic pain after surgery for breast cancer.

The prevalence of the postmastectomy pain syndrome (PMPS) and its clinical characteristics was assessed in a group of patients who had undergone surgery for breast cancer at the Department of Surgery, Odense University Hospital, within the period of 1 May 2003 to 30 April 2004. The study included 258 patients and a reference group of 774 women. A questionnaire was mailed to the patients 1 1/2 year after surgery and to the women in the reference group. The PMPS was defined as pain located in the area of the surgery or ipsilateral arm, present at least 4 days per week and with an average intensity of at least 3 on a numeric rating scale from 0 to 10. The prevalence of PMPS was found to be 23.9%. The odds ratio of developing PMPS was 2.88 (95% confidence interval 1.84-4.51). Significant risk factors were as follows: having undergone breast surgery earlier (OR 8.12), tumour located in the upper lateral quarter (OR 6.48) and young age (OR 1.04). This study shows that, although recent advances in the diagnostic and surgical procedures have reduced the frequency of the more invasive surgical procedures, there still is a considerable risk of developing PMPS after treatment of breast cancer.

Effect of levetiracetam on the postmastectomy pain syndrome.

BACKGROUND AND PURPOSE: The aim of this randomized, double-blind, placebo-controlled, cross-over study was to test whether levetiracetam relieves the postmastectomy pain syndrome (PMPS). METHODS: Postmastectomy pain syndrome was defined as pain of neuropathic character located in the area of the surgery and/or the ipsilateral arm. The inclusion criteria were: age more than 18 years, characteristic symptoms corresponding to PMPS more than 6 months after surgery for breast cancer, pain duration more than 3 months, peripheral nerve lesions confirmed by abnormal neurological and quantitative sensory tests, intensity of pain more than 4 on a numeric rating scale from 0 to 10 and pain present at least 4 days a week. RESULTS: Forty-nine patients were screened for participation and 27 patients were included in the study. Twenty-five patients completed two treatment phases of 4 weeks duration with levetiracetam (3000 mg/day) and placebo. There was no difference in the rating of pain relief between treatment with levetiracetam (P = 0.83) and placebo nor when adjusted for possible period effect (P = 0.60). Analysis defining response as pain relief more than 4 on an eleven-point numeric rating scale showed no significant difference between treatment with levetiracetam and placebo (P = 1.00). CONCLUSIONS: Levetiracetam apparently does not relieve peripheral neuropathic pain in PMPS.

Algorithm for neuropathic pain treatment: an evidence based proposal.

New studies of the treatment of neuropathic pain have increased the need for an updated review of randomized, double-blind, placebo-controlled trials to support an evidence based algorithm to treat neuropathic pain conditions. Available studies were identified using a MEDLINE and EMBASE search. One hundred and five studies were included. Numbers needed to treat (NNT) and numbers needed to harm (NNH) were used to compare efficacy and safety of the treatments in different neuropathic pain syndromes. The quality of each trial was assessed. Tricyclic antidepressants and the anticonvulsants gabapentin and pregabalin were the most frequently studied drug classes. In peripheral neuropathic pain, the lowest NNT was for tricyclic antidepressants, followed by opioids and the anticonvulsants gabapentin and pregabalin. For central neuropathic pain there is limited data. NNT and NNH are currently the best way to assess relative efficacy and safety, but the need for dichotomous data, which may have to be estimated retrospectively for old trials, and the methodological complexity of pooling data from small cross-over and large parallel group trials, remain as limitations.