Insights into the pathophysiology and response of persistent spinal pain syndrome type 2 to spinal cord stimulation: a human genome-wide association study.

BACKGROUND: Spinal cord stimulation (SCS) provides pain relief for some patients with persistent spinal pain syndrome type 2 (PSPS 2), but the precise mechanisms of action and prognostic factors for a favorable pain response remain obscure. This in vivo human genome-wide association study provides some pathophysiological clues. METHODS: We performed a high-density oligonucleotide microarray analysis of serum obtained from both PSPS 2 cases and pain-free controls who had undergone lower back spinal surgery at the study site. Using multivariate discriminant analysis, we tried to identify different expressions between mRNA transcripts from PSPS 2 patients relative to controls, SCS responders to non-responders, or SCS responders to themselves before starting SCS. Gene ontology enrichment analysis was used to identify the biological processes that best discriminate between the groups of clinical interest. RESULTS: Thirty PSPS 2 patients, of whom 23 responded to SCS, were evaluated together with 15 pain-free controls. We identified 11 significantly downregulated genes in serum of PSPS 2 patients compared with pain-free controls and two significantly downregulated genes once the SCS response became apparent. All were suggestive of enhanced inflammation, tissue repair mechanisms and proliferative responses among the former. We could not identify any gene differentiating patients who responded to SCS from those who did not respond. CONCLUSIONS: This study points out various biological processes that may underlie PSPS 2 pain and SCS therapeutic effects, including the modulation of neuroimmune response, inflammation and restorative processes.

Effect of Conventional Spinal Cord Stimulation on Serum Protein Profile in Patients With Persistent Spinal Pain Syndrome: A Case-Control Study.

BACKGROUND: Spinal cord stimulation (SCS) provides pain relief for most patients with persistent spinal pain syndrome type 2 (PSPS 2). Evidence is mounting on molecular changes induced by SCS as one of the mechanisms to explain pain improvement. We report the SCS effect on serum protein expression in vivo in patients with PSPS 2. MATERIALS AND METHODS: Serum proteins were identified and quantified using mass spectrometry. Proteins with significantly different expression among patients with PSPS 2 relative to controls, responders, and nonresponders to SCS, or significantly modulated by SCS relative to baseline, were identified. Those most correlated with the presence and time course of pain were selected using multivariate discriminant analysis. Bioinformatic tools were used to identify related biological processes. RESULTS: Thirty patients with PSPS 2, of whom 23 responded to SCS, were evaluated, together with 14 controls with no pain who also had undergone lumbar spinal surgery. A significant improvement in pain intensity, disability, and quality of life was recorded among responders. Five proteins differed significantly at baseline between patients with PSPS 2 and controls, with three proteins, mostly involved in immune processes and inflammation, being downregulated and two, mostly involved in vitamin metabolism, synaptic transmission, and restorative processes, being upregulated. In addition, four proteins, mostly related to immune processes and inflammation, decreased significantly, and three, mostly related to iron metabolism and containment of synaptic sprouting, increased significantly during SCS. CONCLUSION: This study identifies various biological processes that may underlie PSPS 2 pain and SCS therapeutic effects, including the modulation of neuroimmune response and inflammation, synaptic sprouting, vitamin and iron metabolism, and restorative processes.

Differences in Gene Expression of Endogenous Opioid Peptide Precursor, Cannabinoid 1 and 2 Receptors and Interleukin Beta in Peripheral Blood Mononuclear Cells of Patients With Refractory Failed Back Surgery Syndrome Treated With Spinal Cord Stimulation: Markers of Therapeutic Outcomes?

OBJECTIVE: The use of spinal cord stimulation for patients with failed back surgery syndrome (FBSS) is very common. In order to better understand the mechanisms of action of spinal cord stimulation (SCS), our aim was to determine potential changes in relative gene and protein expression in the peripheral blood mononuclear cells (PBMCs) of patients as potential biomarkers of disease outcomes and potential new targets for therapy. METHODS: Twenty-four patients with diagnosis of FBSS refractory to conservative therapy for at least six months were included in the study. Clinical evaluation in this study included validated questionnaires. Blood samples (10 mL) were collected five times from baseline until two months after implant of the leads. Proenkephalin (PENK), cannabinoid receptors CB1 and CB2, and interleukin 1ß (IL 1ß) were analyzed. Each patient served as his/her own control by comparing the samples collected at different time points against the baseline sample collected at T0. RESULTS: A total of 16 patients met all relevant criteria during the whole study and were assessed. Only PENK showed significant changes over time (Friedman p = 0.000). A positive correlation was observed between changes in visual analog scale (VAS) scores and PENK and a negative correlation between changes in PENK and Short Form-12 (SF-12) mental component score (MCS) scores, as well as between changes in IL 1ß and Pain Detect Questionnaire (PD-Q) scores. As PENK changes increased, so did pain (VAS). As changes in PENK increased, SF-12 MCS health worsened. As changes in IL 1ß increased, PD-Q values decreased. No severe adverse events occurred. CONCLUSIONS: Previously unknown effects of SCS on levels of PBMCs biomarkers are demonstrated. The findings of our research suggest a potential for useful integration of genome analysis and lymphocyte expression in the daily practice of neurostimulation for pain management and represent a novel road map in the light of the important questions that remain unanswered.

Manejo del dolor irruptivo asociado a la cura de úlceras cutáneas / Management of breakthrough pain associated with the cure of skin ulcers

OBJETIVOS: Valorar el manejo profiláctico del dolor irruptivo asociado a la cura de úlceras cutáneas, teniendo en cuenta los diferentes tratamientos que se usan en la práctica clínica para la prevención y la reducción del dolor. MATERIAL Y MÉTODOS: Estudio multicéntrico, observacional y transversal. El estudio se llevó a cabo en 11 hospitales en España. Se recopilaron datos sobre las características de las úlceras, además de variables demográficas y clínicas de los pacientes. La valoración del dolor, la ansiedad y la satisfacción del paciente se midieron mediante el cuestionario del dolor de McGill, la escala de ansiedad de Hamilton y escalas visuales analógicas. RESULTADOS: La mayoría de los pacientes presentaba niveles bajos de ansiedad (74,2 %, ninguna o leve), mientras que la satisfacción de los pacientes y los profesionales sanitarios era alta (8,3 y 7,7, respectivamente). Se administraron medicamentos opioides al 73,8 % de los pacientes, que experimentaron significativamente (p < 0,0001) menos dolor que aquellos que no recibieron tratamiento o que recibieron medicamentos no opioides. El tipo de tratamiento se relacionó con la edad del paciente, la percepción del dolor durante la cura, los años de experiencia del profesional, el uso de guías clínicas y el servicio o unidad en el que se llevó a cabo la cura. El uso de profilaxis se relacionó significativamente con el tratamiento del dolor irruptivo, con úlceras más graves y con el tratamiento realizado por un profesional con menos de 20 años de experiencia, que siguió las guías clínicas. Otros factores relacionados con el uso de opioides fueron la presencia de ansiedad, la unidad donde se realizaron los cuidados y los años de experiencia del profesional de la salud. CONCLUSIONES: Las diferencias en el manejo del paciente dependieron de numerosos factores. La profilaxis con opioides se asoció con una menor percepción del dolor para el paciente

OBJECTIVE: to assess the prophylactic management of breakthrough pain associated with skin ulcers care procedures, considering the different treatments used in clinical practice for the prevention and minimization of pain. MATERIAL AND METHODS: A multicenter, cross-sectional, observational study. The study was conducted in 11 hospitals distributed throughout Spain. Ulcer features, patient demographics and clinical characteristics were recorded. Pain assessment, and patients' anxiety and satisfaction were measured using McGill Pain Questionnaire, Hamilton Anxiety Rating Scale and visual analogue scales (VAS). RESULT: Low levels of anxiety were registered (74.2%, none or mild) and patient and healthcare professional satisfaction was high (8.3 and 7.7, respectively). Opioid drugs were administered to 73.8% of patients, who experienced significantly less pain than those who did not receive treatment or who received non-opioid drugs (p < 0.0001). Type of management was related to patient age, ulcer characteristics, treatment for background pain, patient anxiety levels, perception of pain during the procedure, years of experience of the healthcare professional, the use of clinical guidelines, and the unit in which it was performed. Factors significantly related to the use of prophylaxis were treatment for background pain, more severe ulcers, and treatment by a professional with <20 years of experience who followed clinical guidelines. Significant factors related to the use of opioids were anxiety, the care unit, and the years of experience of the healthcare professional. CONCLUSIÓN: Differences in patient management depended on numerous factors. Prophylaxis with opioids, mainly fentanyl, resulted in less pain for the patient

Stability of a Parenteral Formulation of Betamethasone and Levobupivacaine.

Background: The therapeutic management of syndromes presenting simultaneously pain and inflammation often requires the administration of anesthetic and corticosteroid drugs by epidural administration. In this article, we studied a mixture that combines betamethasone and levobupivacaine, which demonstrates prolonged analgesic effects. To our knowledge, the stability of such a mixture in epidural solution has not been examined. Objective: To evaluate the chemical, physical, and microbiological stability of an extemporaneously prepared mixture. Methods: A solution of betamethasone acetate 1 mg/mL, betamethasone phosphate 1 mg/mL, and levobupivacaine hydrochloride 0.83 mg/mL was prepared in saline. The components were analyzed by high-performance liquid chromatography for up to 270 days of storage, protected and exposed to light, at room temperature, and stored in the refrigerator and at 45°C. In addition, sterility, organoleptic properties, and pH of the admixture were monitored. Results: There are no significant differences between drug concentrations obtained at room temperature and at refrigerated temperature. The accelerated conditions (45°C) demonstrated different results among the actives: betamethasone acetate and levobupivacaine hydrochloride are affected while betamethasone phosphate remains stable. The stability of the mixture does not depend on light exposure. The validity period of the different components in the mixture was estimated as 120 days for betamethasone phosphate and 163 days for levobupivacaine hydrochloride; betamethasone acetate remained unchanged during 155 days. Conclusion: Analgesic mixtures of betamethasone and levobupivacaine can be stored at ambient temperature in polypropylene vials for up to 120 days at the studied concentrations. These data enable the rationalization of the centralized preparation in the hospital pharmacy.

Mejora de la calidad de vida de pacientes con dolor crónico no oncológico por el seguimiento farmacoterapéutico desde la farmacia comunitaria / No disponible

No disponible

Tratamiento farmacológico del trastorno del sueño en la fibromialgia / No disponible

La fibromialgia es una patología crónica y compleja que provoca dolor muscular generalizado que puede llegar a ser invalidante, asociado a mal descanso nocturno y fatigabilidad, y que afecta a las esferas biológica, psicológica y social de los pacientes. Además su elevada prevalencia hace de ella un problema sanitario de primera magnitud. Dificultad añadida supone el que sus criterios diagnósticos únicamente sean clínicos y que su etiopatogenia todavía no haya sido aclarada, lo que dificulta aún más su estudio y por supuesto su abordaje terapéutico. Los múltiples síntomas que acompañan a esta enfermedad, su elevada incidencia y el desconocimiento de su etiología y tratamiento adecuados enfatizan la necesidad de un abordaje multidisciplinar, donde el equipo asistencial, incluido el farmacéutico, promoverá el uso racional de las medidas farmacológicas y fomentará aquellas medidas no farmacológicas que mejoren la calidad de vida del enfermo de fibromialgia (AU)

Fibromyalgia is a chronic and complex pathology that provokes muscular pain which may become invalidant, associated to a badly night rest and fatigue that affects the biological, psychological and social environment of the patients. Its high prevalence makes fibromyalgia a first magnitude sanitary problem. The fact that its diagnostic criteria be only clinical, and that its aetiopathogenesis has not yet been clarified, makes it difficult its study and therapeutical approach. A multidisciplinary approach is necessary because of the multiple symptoms, the high number of cases and the low knowledge of the etiology and the satisfactory treatment. The care team, including pharmacist, will promote the rational use of the pharmacological and the not pharmacological measures that improve de quality of life (AU)