Capsaicin 8% dermal patch in clinical practice: an expert opinion.

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.

Comparison of Tonic vs. Burst Spinal Cord Stimulation During Trial Period.

BACKGROUND: Spinal cord stimulation (SCS) is a well-known treatment in patients with failed back surgery syndrome (FBSS). Burst stimulation is a recently developed stimulation modality that seems to be superior to tonic stimulation. METHODS: This observational multicenter study compared tonic and burst stimulation during a trial period in patients with FBSS or radiculopathy. All the patients enrolled underwent two weeks of tonic stimulation followed by another two weeks of BurstDR stimulation, without randomization. The primary outcome was the reduction of pain in the legs and back. Health-related quality of life (EQ-5D) and the pain catastrophizing scale (PCS) were assessed before and after the trial. Patients were reevaluated after 12 months. RESULTS: We recruited 23 patients, 57% of whom had FBSS and 43% had radiculopathies. Five patients failed both the tonic and burst stimulation trials. While tonic stimulation reduced leg pain (p < 0.05), the burst mode added an extra pain reduction (ΔNRS 1.2 ± 1.5) (p < 0.01). No significant reduction in back pain was found (p 0.29). Pain on movement was reduced only by BurstDR (p < 0.01). Both stimulation modalities increased EQ-5D and reduced PCS from the baseline (p < 0.0001). At the end of the SCS trial phase, 26% patients chose tonic SCS, while 74% preferred burst. On 12-month follow-up examination, the benefits recorded at the end of the trial were maintained. CONCLUSIONS: Burst stimulation confers a greater reduction in leg pain intensity at rest and on movement. Reducing axial pain is still a challenge. Further studies are needed in order to provide each patient with the most appropriate stimulation paradigm.

Benefits in pain perception, ability function and health-related quality of life in patients with failed back surgery syndrome undergoing spinal cord stimulation in a clinical practice setting.

BACKGROUND: Failed back surgery syndrome (FBSS) represents one main cause of chronic neuropathic or mixed pain, functional disability and reduced Health Related Quality of Life (HRQoL). Spinal Cord Stimulation (SCS) can be a value for money option to treat patients refractory to conventional medical management (CMM). We estimated from real-world data: 1) the amount of reduced levels of HRQoL of target patients compared to general population, 2) the relationship between pain intensity, functional disability, and overall HRQoL, and 3) the improvement of patients' health from SCS intervention, and 4) we give some insights and make some suggestions on the selection of a battery of patients' reported health instruments for use in routine clinical practice. METHODS: At recruitment (before SCS) and every 6 months for 2 years after SCS a battery of questionnaires/tests were completed: the generic EQ-5D and SF-36 for HRQoL, the specific Numerical Rating Scale (NRS) to measure pain intensity, and Oswestry Disability Index (ODI) to measure functional disability. We conducted multilevel regression analyses to investigate the association of HRQoL with the NRS and ODI indexes; multiple regression analyses to compare EQ-5D data with those of the general population adjusted for age, sex and education, and statistical tests to compare the changes of HRQoL, NRS and ODI estimates at baseline with those measured during the follow-up. RESULTS: Eighty patients (40% male, mean age = 58 years) participated. HRQoL was significantly worse in the patients than in the corresponding general population. Pain, functional disability and HRQoL significantly related each other during follow-up, Significant improvements (p < 0.001) in pain intensity, functional capability and HRQoL were reached after 6 months from SCS and generally remained stable during follow-up. Specific instruments provided detailed information on disability and pain, while generic instruments assessed the overall HRQoL and allowed a comparison with the general population's one. CONCLUSIONS: SCS + CMM treatment reaches a statistically significant and probably a clinically relevant improvement in pain perception, functional disability and HRQoL in patients with FBSS refractory to CMM. An appropriate selection of instruments for use in clinical practice is crucial for a routine assessment of health perception in patients, aimed to guide decisions for optimal treatment.

Cost-Effectiveness and Cost-Utility Analysis of Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome: Results From the PRECISE Study.

OBJECTIVE: To assess the cost-effectiveness and cost-utility of Spinal Cord Stimulation (SCS) in patients with failed back surgery syndrome (FBSS) refractory to conventional medical management (CMM). MATERIALS AND METHODS: We conducted an observational, multicenter, longitudinal ambispective study, where patients with predominant leg pain refractory to CMM expecting to receive SCS+CMM were recruited in 9 Italian centers and followed up to 24 months after SCS. We collected data on clinical status (pain intensity, disability), Health-Related Quality-of-Life (HRQoL) and on direct and indirect costs before (pre-SCS) and after (post-SCS) the SCS intervention. Costs were quantified in € 2009, adopting the National Health Service's (NHS), patient and societal perspectives. Benefits and costs pre-SCS versus post-SCS were compared to estimate the incremental cost-effectiveness and cost utility ratios. RESULTS: 80 patients (40% male, mean age 58 years) were recruited. Between baseline and 24 months post-SCS, clinical outcomes and HRQoL significantly improved. The EQ-5D utility index increased from 0.421 to 0.630 (p < 0.0001). Statistically significant improvement was first observed six months post-SCS. Societal costs increased from €6600 (pre-SCS) to €13,200 (post-SCS) per patient per year. Accordingly, the cost-utility acceptability curve suggested that if decision makers' willingness to pay per Quality-Adjusted-Life-Years (QALYs) was €60,000, SCS implantation would be cost-effective in 80% and 85% of cases, according to the NHS's and societal point of views, respectively. CONCLUSIONS: Our results suggest that in clinical practice, SCS+CMM treatment of FBSS patients refractory to CMM provides good value for money. Further research is encouraged in the form of larger, long-term studies.

Breakthrough pain in patients referred to pain clinics: the Italian pain network retrospective study.

INTRODUCTION: Despite breakthrough pain (BTP) being one of the most severe forms of pain, there are no definitive data on its prevalence. METHODS: The authors performed a retrospective survey of the prevalence of BTP in consecutive patients in four Italian pain clinics, subsequent to application of an Italian law mandating detailed clinical records on pain characteristics, treatment, and results. Mean pain intensity was assessed with a numerical rating scale from 0 to 10. RESULTS: The authors analyzed records of 1,401 patients (58% women, 33.1% patients with cancer). Transient episodes of severe pain or BTP were referred by 790 patients (56.4%), including 58.2% of the men (342 of 588) and 55.1% of the women (448 of 813). Among the 464 patients with cancer, 70.3% reported daily exacerbation of pain. The mean BTP intensity was 8.31 ± 1.58 and 31.1% of patients reported experiencing three episodes per day. CONCLUSION: Despite some limitations of the study, the authors show that transient episodes of severe pain or BTP are significantly present both in cancer and other diseases, and that many patients are not yet receiving appropriate opioid therapy. The authors need validated tools at international level for the diagnosis and treatment of BTP in patients with cancer and for transitory and patients with severe non-cancer pain. A survey at national level is needed to estimate the prevalence of BTP in different settings, to plan specific medical education.

Spinal cord stimulation for the treatment of chronic pain in patients with lumbar spinal stenosis.

OBJECTIVE: Chronic back and leg pain associated with lumbar spinal stenosis (LSS) is common in the elderly. Surgical decompression is usually performed when conservative treatments fail. We present an evaluation of the long-term outcome of patients suffering from symptomatic LSS treated with spinal cord stimulation (SCS). MATERIALS AND METHODS: Data were collected prospectively in three independent registries in three European centers. Pooled data were analyzed retrospectively. Changes in pain intensity, functional status, and analgesic medication were compared at baseline and at the last available follow-up. Demographic data as well as details regarding the implantation procedure and any adverse events were systematically recorded. RESULTS: Data were recorded in 69 patients with a mean follow-up period of 27 months. All patients showed clinically and statistically significant improvement in pain relief, the visual analog scale decreasing from 7.4 ± 2.3 to 2.8 ± 2.4 (p < 0.05). The use of analgesic medication decreased and the functional status improved. CONCLUSION: Spinal cord stimulation seems to be effective in the treatment of patients suffering from chronic pain associated with LSS. Being less invasive and reversible, SCS should be considered before surgical decompression, particularly in patients with increased risks associated with back surgery.

The restore rechargeable, implantable neurostimulator: handling and clinical results of a multicenter study.

BACKGROUND: Spinal cord stimulation is an effective therapy for chronic, neuropathic pain refractory to medication. Use of a rechargeable neurostimulation system (Restore, Medtronic Inc) could provide greater longevity in the treatment of complex pain. However, patients' ability to successfully recharge a neurostimulation system has not yet been demonstrated. PRIMARY OBJECTIVE: Ability of patients to recharge the neurostimulator. SECONDARY OBJECTIVES: Patient and physician satisfaction with the system, pain relief, quality of life, functional status, adverse events. METHODS: Prospective, open-label, multicenter, European study in patients with long-term refractory neuropathic pain. Recharging ability was assessed 1-month postimplant. Patient and physician satisfaction, pain relief, quality of life, and functional status were assessed at scheduled follow-up visits through 12 months. Adverse events were monitored throughout. RESULTS: Primary end point: 100% of patients (n=41) successfully recharged the neurostimulator. Secondary end points at 1 month: 78.6% of patients found recharging easy. At 12 months: physicians were satisfied with the system for 92.7% of patients; pain intensity decreased significantly (P<0.001); mean self-reported pain relief was 62%; 80.5% of patients had more than 50% pain relief; quality of life and functional status improved significantly (P<0.001); 98% of patients would recommend spinal cord stimulation to others. Overall, 41 device-related complications (23 patients) were observed. CONCLUSIONS: Twelve-month experience indicates that the rechargeable neurostimulation system (Restore) was easy to use, with 100% of patients able to recharge successfully. Patient and physician satisfaction was high, with significant improvements in pain, quality of life, and functional status. Complications were comparable to prior experience with this therapy.

Spinal cord stimulation in hemodialysis patients with critical lower-limb ischemia.

BACKGROUND: Spinal cord stimulation (SCS) has been proposed for the treatment of ischemic pain and the prevention or delay of amputation in patients with peripheral arterial occlusive disease (PAOD) who are unsuitable for vascular reconstruction. PAOD is common in patients with end-stage renal disease and is associated with substantial morbidity and mortality. Furthermore, many patients are not candidates for limb-sparing procedures and have to undergo primary amputation. METHODS: We report our experience with SCS in 8 hemodialysis patients with chronic lower-limb ischemia and not suitable for either primary surgical or angioplastic intervention or reintervention. Intensity of ischemic pain, quality of life, use of analgesic medications, limb survival, and outcome of skin ischemic lesions were evaluated before implantation of an SCS device and after 6 and 12 months of follow-up. RESULTS: No complications from SCS device implantation occurred. Both intensity of pain and quality of life significantly improved during follow-up. SCS allowed a decrease in pain medication intake in all patients. Limb survival at 1 year was 75%. Ischemic skin lesions before implantation of an SCS device did not ameliorate during the follow-up period, but the appearance of new lesions was not observed. CONCLUSION: Implantation of an SCS device in patients with end-stage renal disease with critical limb ischemia dramatically improves quality of life and pain relief. In patients assessed at Leriche-Fontaine stage 2 or 3, the treatment might delay the appearance of ischemic skin lesions and amputation. At these stages, presumed long-term benefits could justify the cost of SCS.