ObjectiveTo 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 MethodsWe 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.Results80 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.ConclusionsOur 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.

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Background Spinal cord stimulation (SCS) is an established treatment for chronic neuropathic, neuropathic‐like and ischaemic pain. However, the heterogeneity of patients in daily clinical practice makes it often challenging to determine which patients are eligible for this treatment, resulting in undesirable practice variations. This study aimed to establish patient‐specific recommendations for referral and selection of SCS in chronic pain. Methods A multidisciplinary European panel used the RAND/UCLA Appropriateness Method (RUAM) to assess the appropriateness of (referral for) SCS for 386 clinical scenarios in four pain areas: chronic low back pain and/or leg pain, complex regional pain syndrome, neuropathic pain syndromes and ischaemic pain syndromes. In addition, the panel identified a set of psychosocial factors that are relevant to the decision for SCS treatment. Results Appropriateness of SCS was strongly determined by the neuropathic or neuropathic‐like pain component, location and spread of pain, anatomic abnormalities and previous response to therapies targeting pain processing (e.g. nerve block). Psychosocial factors considered relevant for SCS selection were as follows: lack of engagement, dysfunctional coping, unrealistic expectations, inadequate daily activity level, problematic social support, secondary gain, psychological distress and unwillingness to reduce high‐dose opioids. An educational e‐health tool was developed that combines clinical and psychosocial factors into an advice on referral/selection for SCS. Conclusions The RUAM was useful to establish a consensus on patient‐specific criteria for referral/selection for SCS in chronic pain. The e‐health tool may help physicians learn to apply an integrated approach of clinical and psychosocial factors. Significance Determining the eligibility of SCS in patients with chronic pain requires careful consideration of a variety of clinical and psychosocial factors. Using a systematic approach to combine evidence from clinical studies and expert opinion, a multidisciplinary European expert panel developed detailed recommendations to support appropriate referral and selection for SCS in chronic pain. These recommendations are available as an educational e‐health tool (https://www.scstool.org/).

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Patient-controlled analgesia using a PTM with a programmable, implantable pump system is an effective therapy for the treatment of chronic pain and allows patients to feel that they have more control over unpredictable pain fluctuations.

Bonezzi C, Demartini L. Treatment options in postherpetic neuralgia. Acta Neurol Scand 1999: Suppl. 173: 25-35. Postherpetic neuralgia (PHN) is a separate disease entity that represents a complication of acute herpes zoster. PHN, involving aberrant somatosensory processing in the peripheral and/or central nervous system, is considered to be a chronic neuropathic pain, frequently unresponsive to all treatment modalities. Despite the clinical trial data demonstrating successful pain relief with several drug regimens, the pharmacologic management of neuropathic pain is difficult, particularly in PHN. Response to therapy is generally inhomogeneous. Some patients experience longterm pain control with either topical or oral monotherapy with antidepressants, anticonvulsants, or opioids. Other PHN patients, such as those suffering pain due to central nervous system lesions, are extraordinarily refractory to all measures. This article will review current treatmentstricyclic antidepressants, anticonvulsants, local anesthetics, clonidine, N-methyl+-aspartate (NMDA)-antagonists, and opioidsand focus on mechanism-based pharmacologic interventions. Pharmacologic approaches can be classified into three groups: 1) drugs that act topically in the affected skin area; 2) drugs that act on nerve excitability and conduction in sensory axons; and 3) drugs that act on neural damage-related synaptic changes. This last group is the only pain treatment option related to central denervation. To date, the treatment of PHN has relied on the use of tricyclic antidepressants (TCAs), which represent the most comprehensively studied medications for this pain syndrome. Clinical data indicate that TCAs are effective analgesics in approximately 50% of patients; these drugs have been recommended as first-line agents for all neuropathic pain syndromes except trigeminal neuralgia, but are frequently contraindicated or poorly tolerated in elderly patients with PHN. If monotherapy fails, a mechanism-and/or symptom-based multidrug regimen can be used. There is also consistent support for intravenous and topical lidocaine, intravenous ketamine, carbamazepine, and opioids. Gabapentin, a new anticonvulsant, can be considered a first-line oral medication for PHN based on the efficacy and safety results of a recently completed double-blind trial. In addition to positive effects on PHN, sleep, mood, and overall quality of life were significantly improved. neuralgia

Mosquitoes can learn to change their host-feeding behaviors, such as shifting activity times to avoid bednets or switching from biting animals to biting humans, leading to the transfer of zoonotic diseases. Dopamine is critical for insect learning, but its role in the antennal lobe remains unclear, and it is unknown whether different mosquito species learn the same odor cues. We assayed aversive olfactory learning and dopaminergic brain innervation in four mosquito species with different host preferences and report here that they differentially learn odors salient to their preferred host and innervation patterns vary across species. Using genetically-encoded GCaMP6s Aedes aegypti, we mapped odor-evoked antennal lobe activity and report that glomeruli tuned to "learnable" odors have significantly higher dopaminergic innervation. Changes in dopamine expression in the antennal lobes of diverse invertebrate species may be an evolutionary mechanism to adapt olfactory learning circuitry without changing brain structure and for mosquitoes an ability to adapt to other hosts when their preferred are no longer present.

BackgroundFailed 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.MethodsAt 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.ResultsEighty 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.ConclusionsSCS + 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.