Remyelination in humans due to a retinoid-X receptor agonist is age-dependent.

Remyelination efficiency declines with advancing age in animal models, but this has been harder to demonstrate in people with multiple sclerosis. We show that bexarotene, a putatively remyelinating retinoid-X receptor agonist, shortened the visual evoked potential latency in patients with chronic optic neuropathy aged under 42 years only (with the effect diminishing by 0.45 ms per year of age); and increased the magnetization transfer ratio of deep gray matter lesions in those under 43 years only. Addressing this age-related decline in human remyelination capacity will be an important step in the development of remyelinating therapies that work across the lifespan.

The time to develop treatments for diabetic neuropathy.

BACKGROUND: Diabetic neuropathy is a multifaceted condition affecting up to 50% of individuals with long standing diabetes. The most common presentation is peripheral diabetic sensory neuropathy (DPN). METHODS: We carried out a systematic review of papers dealing with diabetic neuropathy on Pubmed in addition to a targeted Google search.Search terms included small fiber neuropathy,diffuse peripheral neuropathy, quantitative sensory testing, nerve conduction testing, intra-epidermal nerve fiber density, corneal confocal reflectance microscopy, aldose reductase inhbitors, nerve growth factor, alpha-lipoic acid, ruboxistaurin, nerve growth factor antibody, and cibinetide. RESULTS: Over the past half century, there have been a number of agents undergoing unsuccessful trials for treatment of DPN.There are several approved agents for relief of pain caused by diabetic neuropathy, but these do not affect the pathologic process. EXPERT OPINION: The failure to find treatments for diabetic neuropathy can be ascribed to (1) the complexity of design of studies and (2) the slow progression of the condition, necessitating long duration trials to prove efficacy.We propose a modification of the regulatory process to permit early introduction of agents with demonstrated safety and suggestion of benefit as well as prolongation of marketing exclusivity while long term trials are in progress to prove efficacy.

Botulinum Toxin and Neuronal Regeneration after Traumatic Injury of Central and Peripheral Nervous System.

Botulinum neurotoxins (BoNTs) are toxins produced by the bacteria Clostridiumbotulinum, the causing agent for botulism, in different serotypes, seven of which (A-G) are well characterized, while others, such as H or FA, are still debated. BoNTs exert their action by blocking SNARE (soluble N-ethylmale-imide-sensitive factor-attachment protein receptors) complex formation and vesicle release from the neuronal terminal through the specific cleavage of SNARE proteins. The action of BoNTs at the neuromuscular junction has been extensively investigated and knowledge gained in this field has set the foundation for the use of these toxins in a variety of human pathologies characterized by excessive muscle contractions. In parallel, BoNTs became a cosmetic drug due to its power to ward off facial wrinkles following the activity of the mimic muscles. Successively, BoNTs became therapeutic agents that have proven to be successful in the treatment of different neurological disorders, with new indications emerging or being approved each year. In particular, BoNT/A became the treatment of excellence not only for muscle hyperactivity conditions, such as dystonia and spasticity, but also to reduce pain in a series of painful states, such as neuropathic pain, lumbar and myofascial pain, and to treat various dysfunctions of the urinary bladder. This review summarizes recent experimental findings on the potential efficacy of BoNTs in favoring nerve regeneration after traumatic injury in the peripheral nervous system, such as the injury of peripheral nerves, like sciatic nerve, and in the central nervous system, such as spinal cord injury.

Calcitonin gene-related peptide antagonists versus botulinum toxin A for the preventive treatment of chronic migraine protocol of a systematic review and network meta-analysis: A protocol for systematic review.

BACKGROUND: Although calcitonin gene-related peptide antagonists and botulinum toxin A have been shown efficacy in preventing chronic migraine, there is no direct evidence for their comparative effectiveness. This review is to assess the comparative effectiveness and safety of calcitonin gene-related peptide antagonists and botulinum toxin A for chronic migraine using network meta-analysis. METHODS: OVID MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials will be searched for relevant randomized controlled trials from their inception to December 2019 without language restriction. We will include trials testing the effectiveness of calcitonin gene-related peptide antagonists or botulinum toxin A in patients with chronic migraine. The outcomes are mean change from baseline in the number of headache days, the mean change from baseline in the number of migraine days, the mean change from baseline in headache hours, responder rate, and adverse events rate. The methodological quality of the included randomized controlled trials will be evaluated using Cochrane Collaboration's risk of bias tool. Standardized mean difference will be used to synthesize continuous variables and risk ratio will be used to synthesize categorical variables. Pairwise and network meta-analysis will be performed using a frequentist method in netmeta package (R 3.5.0, www.r-project.org). RESULTS: Ethical approval and informed consent are not required for this systematic review. The results will be submitted to a peer-reviewed journal and conference abstracts for publication. CONCLUSION: The result of the review will systematically provide suggestions for clinicians, patients, and policy makers in the treatment of chronic migraine.PROSPERO registration number: CRD42018089201.

Out-of-pocket costs are on the rise for commonly prescribed neurologic medications.

OBJECTIVE: To determine out-of-pocket costs for neurologic medications in 5 common neurologic diseases. METHODS: Utilizing a large, privately insured, health care claims database from 2004 to 2016, we captured out-of-pocket medication costs for patients seen by outpatient neurologists with multiple sclerosis (MS), peripheral neuropathy, epilepsy, dementia, and Parkinson disease (PD). We compared out-of-pocket costs for those in high-deductible health plans compared to traditional plans and explored cumulative out-of-pocket costs over the first 2 years after diagnosis across conditions with high- (MS) and low/medium-cost (epilepsy) medications. RESULTS: The population consisted of 105,355 patients with MS, 314,530 with peripheral neuropathy, 281,073 with epilepsy, 120,720 with dementia, and 90,801 with PD. MS medications had the fastest rise in monthly out-of-pocket expenses (mean [SD] $15 [$23] in 2004, $309 [$593] in 2016) with minimal differences between medications. Out-of-pocket costs for brand name medications in the other conditions also rose considerably. Patients in high-deductible health plans incurred approximately twice the monthly out-of-pocket expense as compared to those not in these plans ($661 [$964] vs $246 [$472] in MS, $40 [$94] vs $18 [$46] in epilepsy in 2016). Cumulative 2-year out-of-pocket costs rose almost linearly over time in MS ($2,238 [$3,342]) and epilepsy ($230 [$443]). CONCLUSIONS: Out-of-pocket costs for neurologic medications have increased considerably over the last 12 years, particularly for those in high-deductible health plans. Out-of-pocket costs vary widely both across and within conditions. To minimize patient financial burden, neurologists require access to precise cost information when making treatment decisions.

Therapeutic strategies that act on the peripheral nervous system in primary headache disorders.

Introduction: Acute and preventive treatment of primary headache disorders is not completely resolved with regard to efficacy, safety, and tolerability. Hence, peripheral and central neuromodulation can provide therapeutic alternatives in drug-resistant cases. Peripheral targets of neuromodulation include invasive and non-invasive neurostimulation and electrical and chemical nerve and ganglion blockades. Areas covered: A PubMed search of papers published from January 2012 to October 2018 was conducted. The goal of this review was to analyze the efficacy and safety of invasive (implantable) peripheral neurostimulation methods (the occipital nerve, the cervical branch of vagal nerve, the sphenopalatine ganglion) and non-invasive (transcutaneous) peripheral neurostimulation methods (the occipital nerve, the supraorbital nerve, and the cervical and auricular branches of the vagal nerve), based on the results of published clinical trials and case series. Acting also on the peripheral nervous system, peripheral nerve (i.e. greater occipital nerve) and ganglion (i.e. sphenopalatine ganglion) blockades, botulinum neurotoxin type A-hemagglutinin complex therapies, and calcitonin gene-related peptide-related monoclonal antibody treatments in this patient population are also discussed. Expert opinion: This review summarizes the latest results on the therapeutic strategies acting on the periphery in primary headache disorders. These therapeutic options are minimally invasive or non-invasive, efficacious, safe, and well tolerated.

The Expanding Therapeutic Utility of Botulinum Neurotoxins.

Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present an overview of the current therapeutic landscape and explore the diversity of BoNT proteins as future therapeutics. In recent years, novel indications have emerged in the fields of pain, migraine, overactive bladder, osteoarthritis, and wound healing. The study of biological effects distal to the injection site could provide future opportunities for disease-tailored BoNT therapies. However, there are some challenges in the pharmaceutical development of BoNTs, such as liquid and slow-release BoNT formulations; and, transdermal, transurothelial, and transepithelial delivery. Innovative approaches in the areas of formulation and delivery, together with highly sensitive analytical tools, will be key for the success of next generation BoNT clinical products.

Efecto de la edad y el género sobre las consecuencias clínicas y económicas del tratamiento con especialidad farmacéutica de marca o genérica en pacientes con dolor neuropático periférico en práctica clínica habitual / Clinical and economic consequences of treating patients with peripheral neuropathic pain with brand name or generic drugs in routine clinical practice: The effects of age and sex

OBJETIVO: Analizar el efecto de la edad y el género sobre el dolor y los costes en pacientes con dolor neuropático periférico (DNp) crónico que inician tratamiento con gabapentina (marca) frente a gabapentina genérica (EFG). MÉTODOS: Estudio multicéntrico-retrospectivo, realizado con registros médicos electrónicos (RME) de pacientes de ambos géneros, > 18años, que iniciaron nuevo tratamiento con gabapentina de marca o genérico. Durante un año se midió la adherencia (ratio posesión medicación [RPM]) y la persistencia, la utilización de recursos sanitarios, los costes y la reducción del dolor. RESULTADOS: Se analizaron 1.369 RME (61,1% mujeres; edad 64,6 [15,9] años, 52,4% ≥ 65 años); marca: 400, EFG: 969. La persistencia y la adherencia fueron mayores con marca: 7,3 vs. 6,3 meses (p < 0,001) y 86,5 vs. 81,3% de RPM (p < 0,001). Con marca, se observaron costes sanitarios menores, tanto en < 65 como en ≥ 65años (diferencias medias por paciente de 221 Euros [IC95%: 59-382] y de 217 Euros [51-382], respectivamente [p < 0,01]), como en hombres (diferencias medias de 197 Euros [63-328]) o mujeres (diferencias de 239 Euros [96-397]), p = 0,005 y p = 0,004, respectivamente. Comparado con EFG, el tratamiento con marca mostró una reducción mayor del dolor: 13,5% (10,9-16,2) y 10,8% (8,2-13,5) en < 65 y ≥ 65 años, respectivamente (p < 0,001), así como del 10,7% (8,2-13,2) y del 13,8% (11,0-16,5) en mujeres y hombres, respectivamente (p < 0,001). CONCLUSIONES: Con independencia del género o la edad, los pacientes que iniciaron tratamiento del DNp con gabapentina de marca vs. genérico mostraron un mayor grado de adherencia y persistencia al tratamiento, repercutiendo en unos menores costes sanitarios, a la vez que se observaron mayores reducciones del dolor

OBJECTIVE: We aimed to analyse the effects of age and sex on pain and cost for patients with chronic peripheral neuropathic pain (PNP) who have started treatment with brand name gabapentin versus generic gabapentin (EFG). METHODS: We conducted a retrospective multicentre study using electronic medical records (EMR) for patients of both sexes, older than 18, who began treatment with brand name or generic gabapentin. Adherence (medication possession ratio [MPR]), persistence, use of healthcare resources, cost, and pain reduction were measured for one year. RESULTS: We analysed 1369 EMRs [61.1% women; mean age 64.6 (15.9), 52.4% ≥ 65 years]; 400 used brand name drugs while 969 used generic gabapentin. Persistence and adherence were higher in patients using brand name gabapentin (7.3 vs 6.3 months, P < .001; 86.5% vs 81.3% MPR, P < .001). Lower healthcare costs were observed in patients using brand-name gabapentin in both age groups (< 65 and ≥ 65). Mean difference in cost per patient amounted to Euros221 (95%CI: 59-382) and Euros 217 (95%CI: 51-382) in the < 65 and ≥ 65 age groups, respectively (P < .01). Mean difference in cost among men amounted to Euros 197 (63-328), while mean difference in cost among women amounted to Euros 239 (96-397) (P = .005 and P = .004, respectively). Compared with EFG, brand treatment showed greater pain relief: 13.5% (10.9-16.2) and 10.8% (8.2-13.5) in < 65 and ≥ 65year patients, respectively (P < .001), and 10.7% (8.2-13.2) and 13.8% (11.0-16.5) in women and men respectively (P < .001). CONCLUSIONS: Regardless of sex and age, patients who started PNP treatment with brand name medication showed greater persistence and adherence to treatment than those taking generic drugs. Brand name treatment also involved lower healthcare costs, and greater pain relief

The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin, and their Combination in Painful Polyneuropathy.

OBJECTIVE: The aim of this study was to explore the serum concentration-effect relation for first-line drugs in neuropathic pain and to determine if efficacy could be increased. METHODS: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin, and their combination in painful polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0 to 10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. RESULTS: In 47 patients, pain was reduced -1.0 (95% confidence interval [CI], -1.5 to -0.6) by imipramine, -0.4 (95% CI, -0.9 to 0.1) by pregabalin, and -1.6 (95% CI, -2.1 to -1.1) by combination therapy. On monotherapy, there was no difference between responders and nonresponders with respect to concentrations of imipramine (mean, 161 vs. 229 nmol/L, P=0.129) and pregabalin (mean, 9.8 vs. 11.7 µmol/L, P=0.178). There was no correlation between drug concentration and pain reduction for imipramine (r=0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine < or ≥100 nmol/L, pregabalin < or ≥10 µmol/L) either for monotherapy or for combination therapy (P=0.161 to 0.797). Isobolographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction. DISCUSSION: There were no important relations between drug concentrations and efficacy, or indication of synergistic interaction between the drugs. It was not concluded that treatment can be improved by measurement of drug concentration of pregabalin.

Resultados sobre la aplicación cráneo-facial del parche de capsaicina 8 % en una serie de 5 casos / Results of the capsaicin 8% patch in craniofacial application in five clinical cases

Los parches de capsaicina al 8 % son una alternativa de segunda línea para el tratamiento del dolor neuropático periférico. Aunque tiene pocos efectos secundarios, no tiene indicación para el tratamiento cráneo-facial debido a la posible irritación de mucosas por la capsaicina. Sólo hemos encontrado tres publicaciones que refieren la aplicación del parche en estas localizaciones, describiendo 7 casos clínicos. Hemos recogido 4 casos en los que se realizan 5 aplicaciones en total, 3 mujeres (repitiendo aplicación en una de ellas) y 1 hombre, entre 58 y 84 años, con los siguientes diagnósticos: necrosis cáustica en labio inferior tras limpieza dental, neuralgia del trigémino y neuropatía postherpética. Tras comprobar ineficacia de otros tratamientos, se propuso el parche de capsaicina al 8 %, con firma previa de los consentimientos informados de la aplicación de parche en régimen de hospital de día y de tratamiento fuera de ficha técnica. Previamente a la aplicación del parche en la zona cutánea dolorosa, se procedió a realizar protección ocular de ambos ojos con parche oftálmico quirúrgico, y de mucosas oral y nasal con mascarilla facial quirúrgica sellada. La protección se mantuvo durante toda la aplicación del parche y se quitó una vez retirado éste y limpiada la zona de aplicación. Únicamente se reportaron 3 efectos secundarios leves del total de las 5 aplicaciones: un paciente presentó piel eritematosa que cedió espontáneamente, otra paciente refirió sensación de quemazón y dolor que cedió con analgesia endovenosa, y otra paciente explicó dolor leve bien tolerado, que cedió de manera espontánea. En ninguno de los casos se apreciaron efectos secundarios a nivel de mucosas. En cuanto a resultados, dos pacientes notaron mejoría durante uno y dos meses, colocando nuevamente el parche en una de ellas, sin lograr esta segunda vez alivio. Las otras dos pacientes no notaron ningún cambio. El tratamiento con parches de capsaicina 8 % en superficies cráneo-faciales parece tener similar eficacia a su aplicación en otras áreas de la piel. Los efectos secundarios en su aplicación en estas superficies son escasos, al igual que en otras aplicaciones corporales. Creemos que con las medidas de precaución adecuadas en las regiones cráneo-faciales, la utilidad clínica observada del parche de capsaicina 8 % lo sitúa como otra opción de tratamiento para dolor neuropático, sin complicaciones añadidas. No obstante, estudios clínicos con mayor número de pacientes deberían llevarse a cabo para confirmar estos hallazgos (AU)

The capsaicin 8 % patch is a secondary line alternative to neuropathic peripheral pain treatment. Although it has few secondary effects, is not indicated in head and facial treatment due to the possibility of the irritation of mucosa. We have only found three publications related with the patch application in those locations, describing 7 clinical cases. We have analyzed 4 cases in which we have applied 5 patches in total. There were 3 women (repeating the application in one of them) and 1 man, between 58 and 84 years old, with the following diagnosis: caustic necrosis in the inferior lip after dental cleaning, trigeminal neuralgia and post-herpetic neuropathy. Inefficacy of other treatments was confirmed, and after that, the capsaicin 8 % patch was proposed. Informed consent of the application of the patch at day clinic and treatment out of technical data sheet were previously signed. Before the patch was applied to the painful cutaneous area, we proceed with ocular protection of both eyes with surgical ophthalmic patch and oral and nasal mucosa protection with surgical mask hermetically seal. That protection was maintained during the whole application of the patch, and was removed once the capsaicin patch was taken off and the application area was cleaned. There were only 3 mild secondary effects of the total 5 applications: one patient showed erythematic skin that was resolved spontaneously, another patient related burn and pain sensation which was solved with endovenous analgesia. Finally, another patient explained mild pain well tolerated, that was resolved also spontaneously. In no cases there were secondary effects in mucosa. Related with the results, 2 patients felt improvement between one and two months, applying again the patch in one of them, not reaching this time relief in the pain. The other 2 patients did not notice any change. The capsaicin 8 % patch treatment in head and facial areas seems to have similar efficacy as the application in other skin areas. Secondary effects in these surfaces are very low, the same as in other corporal locations. We believe that with the adequate preventive measures in head and facial areas, clinical utility observed with capsaicin 8 % patch places it as another treatment option for neuropathic pain, with no complications added. However, clinical studies with a higher number of patients should carry on to confirm these findings (AU)

Amyotrophic Lateral Sclerosis Incidence and Previous Prescriptions of Drugs for the Nervous System.

BACKGROUND: An increased frequency of psychotic disorders in amyotrophic lateral sclerosis (ALS) families compared to controls has been reported. Aim of our study was to assess the relationship between nervous system drugs prescriptions and subsequent onset of ALS in a large Italian population. METHODS: The study population consisted of all subjects over 15 years at the 2001 Italian census, resident in Turin since 1996 (n = 687,324), followed up for ALS occurrence from 2002 to 2014. Exposure to nervous system drugs was measured until 2012, or until 1 year before ALS onset. The association was estimated for ever and cumulative exposure, through Cox proportional Hazards models adjusted for sex, age, education, marital status and drug co-exposure. RESULTS: In the analysis for ever exposure, opioids were significantly inversely associated with ALS risk (hazard ratio (HR) 0.59; 95% CI 0.35-0.97), while antiepileptics (HR 1.35; 95% CI 0.92-2.00) showed a marginally significantly positive association. Examining cumulative exposure, the protective role of opioids associated with more than 4 prescriptions and the risk effect of antiepileptics for over 6 prescriptions was confirmed. CONCLUSIONS: The present study revealed associations of ALS onset with previous exposure to opioids, maybe through the activation of δ receptor and σ receptors and antiepileptics, which are novel findings to our knowledge.

C3 toxin and poly-DL-lactide-ε-caprolactone conduits in the critically damaged peripheral nervous system: a combined therapeutic approach.

INTRODUCTION: Peripheral nerve regeneration over longer distances through conduits is limited. In the presented study, critical size nerve gap bridging with a poly-DL-lactide-ε-caprolactone (PLC) conduit was combined with application of C3 toxin to facilitate axonal sprouting. MATERIALS AND METHODS: The PLC filled with fibrin (n = 10) and fibrin gel loaded with 1-µg C3-C2I and 2-µg C2II (n = 10) were compared to autologous nerve grafts (n = 10) in a 15-mm sciatic nerve gap lesion model of the rat. Functional and electrophysiological analyses were performed before histological evaluation. RESULTS: Evaluation of motor function and nerve conduction velocity at 16 weeks revealed no differences between the groups. All histological parameters and muscle weight were significantly elevated in nerve graft group. No differences were observed in both PLC groups. CONCLUSIONS: The PLCs are permissive for nerve regeneration over a 15-mm defect in rats. Intraluminal application of C3 toxin did not lead to significant enhancement of nerve sprouting.

Outcomes of greater occipital nerve injections in pediatric patients with chronic primary headache disorders.

BACKGROUND: Chronic migraine is common in pediatrics and generally disabling. In adults, infiltration of the area around the greater occipital nerve can provide short- to medium-term benefit in some patients. This study reports the efficacy of greater occipital nerve infiltrations in pediatric patients with chronic primary headache disorders. METHODS: Retrospective chart review of patients <18 years with a chronic primary headache disorder undergoing a first-time injection. Infiltrations were unilateral and consisted of a mixture of methylprednisolone acetate, adjusted for weight, and lidocaine 2%. RESULTS: Forty-six patients were treated. Thirty-five (76%) had chronic migraine, 9 (20%) new daily persistent headache (NDPH), and 2 (4%) a chronic trigeminal autonomic cephalalgia. Medication overuse was present in 26%. Ages ranged from 7 to 17 years. Follow-up data were available for 40 (87%). Overall, 53% (21/40) benefitted, and 52% (11/21) benefitted significantly. Benefit onset ranged from 0 to 14 days, mean 4.7 (SD 4.3), with mean benefit duration of 5.4 (SD 4.9) weeks. In chronic migraine, 62% (18/29) benefitted, and 56% (10/18) significantly benefitted. In NDPH, 33% (3/9) benefitted; 33% (n = 1) significantly. Neither child with a chronic trigeminal autonomic cephalalgia benefitted. In logistic regression modeling, medication overuse, age, sex, and sensory change in the distribution of the infiltrated nerve did not predict outcome. There were no serious side effects. CONCLUSIONS: Greater occipital nerve injections benefitted 53% of pediatric patients with chronic primary headache disorders. Efficacy appeared greater in chronic migraine than NDPH. Given the benign side effect profile, a greater occipital nerve infiltration seems appropriate before more aggressive approaches.

Análisis de la eficacia y seguridad del bloqueo iliofascial continuo para analgesia postoperatoria de artroplastia total de rodilla / No disponible

Objetivo: la importancia del dolor agudo postoperatorio radica en su alta frecuencia, en su inadecuado tratamiento y en las repercusiones que tiene en la evolución y en la recuperación del paciente. El bloqueo iliofascial puede ser una técnica adecuada para analgesia postoperatoria en la artroplastia total de rodilla. El objetivo de este estudio es valorar la eficacia y seguridad del bloqueo iliofascial, en comparación con el bloqueo epidural, a efectos de analgesia postquirúrgica en pacientes sometidos a artroplastia total de rodilla bajo anestesia subaracnoidea. Se valoró además si la realización del bloqueo iliofascial es una técnica analgésica segura, las complicaciones derivadas de la misma, los efectos secundarios y el grado de satisfacción del paciente. Material y métodos: estudio multicéntrico, prospectivo, aleatorio, observacional, controlado, con evaluador ciego, en 54 pacientes, adultos, ASA I-III, de ambos sexos, sometidos a cirugía de artroplastia total de rodilla bajo anestesia intradural. Los pacientes incluidos en el estudio se dividieron en dos grupos, BIF y BE. En el grupo BIF (n = 27) se colocó un catéter iliofascial, mientras que en el otro grupo BE (n = 27) se colocó un catéter epidural lumbar (a nivel L3-L4), en ambos casos para la analgesia postoperatoria continua. Ambos grupos recibieron el mismo protocolo analgésico con paracetamol y metamizol pautados, y rescate con bolos de morfina intravenosa. Se utilizó t-Student para comparar las variables cuantitativas. Se consideró significativo (p < 0,05). Resultados: no hubo diferencias entre ambos grupos en el dolor postoperatorio, medido a través de la escala EVA en la primera hora tras la intervención y a las 8, 12, 24 y 48 horas. El consumo de analgesia suplementaria fue similar en ambos grupos. La facilidad para realizar ambas técnicas fue similar y no se evidenciaron complicaciones relacionadas con ninguna de ellas. Tampoco se encontraron diferencias en los efectos secundarios, en el nivel de bloqueo motor, en el grado de satisfacción por la analgesia recibida o en calidad de sueño. Discusión: según nuestro estudio, tanto el catéter epidural como el catéter iliofascial aportan un buen control del dolor postoperatorio en artroplastia total de rodilla, con un grado de satisfacción por parte de los pacientes de bueno a muy bueno. En base a nuestros resultados, parece que el bloqueo iliofascial es una técnica efectiva y segura, por lo que podría incorporarse al protocolo analgésico de artroplastia de rodilla (AU)

Objective: the importance of acute postoperative pain lies in its high frequency, where inadequate treatment and the impact it has on the evolution and the patient’s recovery. Iliofascial block may be a suitable technique for postoperative analgesia after total knee arthroplasty. The aim of this study is to assess the efficacy and safety of the blockade iliofascial compared with epidural analgesia in postoperative effects in patients undergoing total knee arthroplasty under spinal anesthesia. We also evaluate if the iliofascial block is a safe analgesic technique, the complications, the adverse effects and the patient satisfaction. Material and methods: multicenter, prospective, randomized, observational, controlled, assessor blind, in 54 adult patients, ASA I-III, of both sexes, for total knee arthroplasty under spinal anesthesia. Patients included in the study were divided into two groups, BIF and BE. In the BIF group (n = 27), a iliofascial catheter was placed, while in the other group BE (n = 27), a lumbar epidural catheter (at L3-L4) was placed, both for continuous postoperative analghesia. Both groups received the same protocol with paracetamol and metamizol, and rescue with intravenous morphine bolus. Student t test was used to compare quantitative variables. p < 0.05 was considered significant. Results: There were no differences between groups in postoperative pain measured by VAS scale in the first hour after surgery and at 8, 12, 24 and 48 hours. The supplemental analgesia consumption was similar in both groups. Both techniques were easy and showed no complications related to any of them. No differences in side effects, motor block level, the degree of satisfaction with the analgesia received or sleep quality. Discussion: in our study as the epidural catheter as the catheter iliofascial provide good control of postoperative pain after total knee arthroplasty, with a degree of satisfaction of patients as good to very good. According to our results we think that the iliofascial block seems a safe and effective technique, so we could join to the analgesic protocol of knee arthroplasty (AU)

Chromenopyrazoles: non-psychoactive and selective CB1 cannabinoid agonists with peripheral antinociceptive properties.

The unwanted psychoactive effects of cannabinoid receptor agonists have limited their development as medicines. These CB1-mediated side effects are due to the fact that CB1 receptors are largely expressed in the central nervous system (CNS). As it is known that CB1 receptors are also located peripherally, there is growing interest in targeting cannabinoid receptors located outside the brain. A library of chromenopyrazoles designed analogously to the classical cannabinoid cannabinol were synthesized, characterized, and tested for cannabinoid activity. Radioligand binding assays were used to determine their affinities at CB1 and CB2 receptors. Structural features required for CB1/CB2 affinity and selectivity were explored by molecular modeling. Some compounds in the chromenopyrazole series were observed to be selective CB1 ligands. These modeling studies suggest that full CB1 selectivity over CB2 can be explained by the presence of a pyrazole ring in the structure. The functional activities of selected chromenopyrazoles were evaluated in isolated tissues. In vivo behavioral tests were then carried out on the most effective CB1 cannabinoid agonist, 13 a. Chromenopyrazole 13 a did not induce modifications in any of the tested parameters on the mouse cannabinoid tetrad, thus discounting CNS-mediated effects. This lack of agonistic activity in the CNS suggests that this compound does not readily cross the blood-brain barrier. Moreover, 13 a can induce antinociception in a rat peripheral model of orofacial pain. Taking into account the negative results obtained with the hot-plate test, the antinociception induced by 13 a in the orofacial test could be mediated through peripheral mechanisms.

Estimulación de nervio periférico en el tratamiento de diferentes tipo de cefaleas / Peripheral nerve stimulation in the treatment of various types of headache

Introducción. La cefalea constituye una enfermedad con gran impacto en la calidad de vida y la economía de los países industriales. Una de las teorías fisiopatológicas se encuentra la activación de las fibras aferentes cervicales de los nervios C2-C3. La neuroestimulación periférica aferente de C2-C3, que se provoca en la estimulación del nervio occipital, parece aliviar la cefalea a través de las conexiones trigeminocervicales, y ser una de las causas principales de su eficacia. Material y métodos. Estudio multicéntrico retrospectivo entre abril 2005 y mayo 2009. Se incluyó a los pacientes con cefalea crónica mayor que fueron tratados con neuroestimulación. En todos los pacientes se valoró el tipo de cefalea, el grado de dolor mediante una escala numérica simple, tratamiento médico y episodios de cefalea. Se analizó el porcentaje de test negativos. En los portadores del generador definitivo se valoró la eficacia de la técnica mediante el análisis de la escala numérica simple y el análisis del porcentaje de mejoría subjetiva de los pacientes al mes, 3 meses, 6 meses y 12 meses. Se analizó el grado de cobertura, la satisfacción, la disminución de los episodios y la medicación y las complicaciones. Resultados. Se incluyeron 31 pacientes. El resultado del test fue positivo en el 87%. Existió una disminución significativa (p < 0,001) del dolor desde el momento basal con una mejoría mayor del 50% sostenido del 85,2% y un descenso en la puntuación de la escala numérica simple > 2 puntos en un 96,3% de los casos. Todos los pacientes estaban satisfechos durante el estudio. El 56% de la muestra no tuvo episodios de cefaleas tras el año de estudio y el 47% dejo de tomar medicación. La complicación más frecuente fue la migración del electrodo (AU)

Background and objective. Headache has a great impact on patients quality of life and in industrialized countries there is economic impact as well. One of the pathophysiologic theories to explain headache is activation of afferent C2-C3 nerve fibers. Afferent peripheral nerve stimulation by occipital nerve provocation at C2-C3 seems to alleviate headache by acting on the trigeminocervical complex, which would largely explain the effectiveness of this modality. The aim of this study was to describe peripheral nerve stimulation as an alternative therapy in patients who do not respond to other headache treatments. Material and methods. Multicenter retrospective study between April 2005 and May 2009, analyzing cases of patients treated with nerve stimulation for severe chronic headache. In all patients the medical history included type of headache, intensity of pain on a numerical scale, medical treatment used, and number of headache episodes. We recorded the percentage of patients with negative tests. Patients implanted with a generator assessed effectiveness on the numerical scale; we analyzed the percentage of perceived improvement at 1, 3, 6, and 12 months. We also analyzed the extent of coverage provided by the electrodes, patient satisfaction, reduction in the number of episodes and medication, and complications. Results. Of 31 patients, 87% had positive results, with a significant decrease in pain from baseline (P <. 001); 85.2% reported sustained improvement of >50%, and 96.3% reported a decrease of > 2 points on the pain scale. All patients expressed satisfaction during the period of follow-up. Fifty-six percent had no headaches after a year and 47% had stopped taking medication. The most frequent complication was electrode migration (AU)

Irritable bowel syndrome.

Questions from patients about analgesic pharmacotherapy and responses from the authors are presented to help educate patient sand make them more effective self-advocates. The topics addressed in this issue are the signs, symptoms, and treatment of irritable bowel syndrome (IBS). A discussion of pain management and complementary therapies is included.