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.

Neuroestimulación medular. Análisis de las indicaciones diagnósticas / Spinal cord stimulation. Analysis of the diagnostic indications

INTRODUCCIÓN: La neuroestimulación medular (NM) es una forma de tratamiento del dolor crónico que ha demostrado su efectividad en pacientes que han respondido mal a otras terapias. Las indicaciones actuales para los dispositivos de NM son muy variadas. El objetivo de nuestro estudio es analizar las indicaciones diagnósticas de la terapia con NM durante los últimos 5 años en nuestro hospital, conocer cuáles son las causas de dolor más frecuentes para la indicación del implante del dispositivo y qué porcentaje de mejoría presentan los pacientes, así como estudiar la relación con el género y la edad. MATERIAL Y MÉTODOS: Se trata de un estudio observacional, descriptivo y retrospectivo. Los pacientes fueron identificados desde el registro de actividad quirúrgica de la Unidad del Dolor del Hospital General de Valencia. RESULTADOS: El número final de pacientes incluidos fue de 179. El síndrome de cirugía fallida de espalda (SCFE) fue la indicación diagnóstica en 112 pacientes (62,57 %). La media del porcentaje de mejoría descrita por los pacientes tras el implante del NM fue de 47,99 ± 27,3 %. No se observaron diferencias en la mejoría respecto a la edad o el género. DISCUSIÓN: A pesar de la variabilidad de diagnósticos en los que puede estar indicada esta terapia, es destacable que en más de la mitad de los casos la indicación es por SCFE

INTRODUCTION: Spinal cord stimulation (SCS) is a form of chronic pain treatment that has been shown to be effective in patients who have responded poorly to other therapies. The current indications for SCS devices are very varied. The aim of our study is to analyze the diagnostic indications of SCS therapy during the last 5 years in our hospital, to know the most frequent causes of pain for the indication of the implant of the device and what percentage of improvement patients present, as well as to study the relationship with gender and age. MATERIAL AND METHODS: This is an observational, descriptive, retrospective study. The patients were identified from the surgical activity register of the Pain Unit of the General Hospital of Valencia. RESULTS: The final number of patients included was 179. The Failed back surgery syndrome (FBSS) was the diagnostic indication in 112 patients (62.57 %). The mean percentage of improvement described by the patients after the SCS implant was 47.99 ± 27.3 %. There were no differences in the improvement with respect to age or gender. DISCUSSION: In spite of the variability of diagnoses in which this therapy may be indicated, it is noteworthy that in more than half of the cases the indication is by FBSS

Expression of aquaporins 1 and 5 in a model of ventilator-induced lung injury and its relation to tidal volume.

NEW FINDINGS: What is the central question of this study? Although different studies have attempted to find factors that influence the expression of aquaporins (AQPs) in the lung in different situations, to date no research group has explored the expression of AQP1 and AQP5 jointly in rats mechanically ventilated with different tidal volumes in a model of ventilator-induced lung injury. What is the main finding? Mechanical ventilation with a high tidal volume causes lung injury and oedema, increasing lung permeability. In rats ventilated with a high tidal volume, the pulmonary expression of AQP1 decreases. We analysed the expression of aquaporins 1 and 5 and its relation with tidal volume in a model of ventilator-induced lung injury. Forty-two rats were used. Six non-ventilated animals were killed (control group). The remaining rats were ventilated for 2 h with different tidal volumes (group 7ML with 7 ml kg-1 and group 20ML with 20 ml kg-1 ) and a respiratory rate of 90 breaths min-1 . Lung oedema was measured, and the expression of AQP1 and AQP5 was determined by Western immunoblotting and measurement of mRNA. Lung oedema and alveolar-capillary membrane permeability were significantly increased in the animals of group 20ML compared with the control group. Expression of AQP1 was decreased in groups 7ML and 20ML compared with the control group. In conclusion, mechanical ventilation with a high tidal volume causes lung injury and oedema, increasing lung permeability. In rats ventilated with a high tidal volume, the pulmonary expression of AQP1 decreases.

Increased expression of AQP 1 and AQP 5 in rat lungs ventilated with low tidal volume is time dependent.

BACKGROUND AND GOALS: Mechanical ventilation (MV) can induce or worsen pulmonary oedema. Aquaporins (AQPs) facilitate the selective and rapid bi-directional movement of water. Their role in the development and resolution of pulmonary oedema is controversial. Our objectives are to determine if prolonged MV causes lung oedema and changes in the expression of AQP 1 and AQP 5 in rats. METHODS: 25 male Wistar rats were subjected to MV with a tidal volume of 10 ml/kg, during 2 hours (n = 12) and 4 hours (n = 13). Degree of oedema was compared with a group of non-ventilated rats (n = 5). The expression of AQP 1 and AQP 5 were determined by western immunoblotting, measuring the amount of mRNA (previously amplified by RT-PCR) and immunohistochemical staining of AQPs 1 and 5 in lung samples from all groups. RESULTS: Lung oedema and alveolar-capillary membrane permeability did not change during MV. AQP-5 steady state levels in the western blot were increased (p<0.01) at 2 h and 4 h of MV. But in AQP-1 expression these differences were not found. However, the amount of mRNA for AQP-1 was increased at 2 h and 4 h of MV; and for AQP 5 at 4 h of MV. These findings were corroborated by representative immunohistochemical lung samples. CONCLUSION: In lungs from rats ventilated with a low tidal volume the expression of AQP 5 increases gradually with MV duration, but does not cause pulmonary oedema or changes in lung permeability. AQPs may have a protective effect against the oedema induced by MV.

Computer-tomographic verification of ultrasound-guided piriformis muscle injection: a feasibility study.

BACKGROUND: Approximately 6% to 8% of lumbar pain cases, whether associated with radicular pain or not, may be attributed to the presence of piriformis muscle syndrome. Available treatments, among others, include pharmacotherapy, physical therapy, and injections of different substances into the muscle. Various methods have been used to confirm correct needle placement during these procedures, including electromyography (EMG), fluoroscopy, computed tomography (CT), or magnetic resonance imaging (MRI). Ultrasonography (US) has now become a widely used technique and therefore may be an attractive alternative for needle guidance when injecting this muscle. OBJECTIVE: The objective of this study was to assess the reliability of US in piriformis injection of patients with piriformis syndrome. STUDY DESIGN: Feasibility study; 10 patients with piriformis muscle syndrome were injected with botulinum toxin A using a US-guided procedure. Then patients were administered 2 mL iodinated contrast and were then transferred to the CT scanner, where they underwent pelvic and hip imaging to assess intramuscular distribution of the iodinated contrast. SETTING: Multidisciplinary Pain Management Department in Spain. RESULTS: Of all 10 study patients (8 women, 2 men), 9 had intramuscular or intrafascial contrast distribution. Distribution did not go deeper than the piriformis muscle in any of the patients. The absence of contrast (intravascular injection) was not observed in any case. LIMITATIONS: The main limitation of our study is the use of ionizing radiation as confirmation technique. CONCLUSION: Ultrasound-guided puncture may be a reliable and simple procedure for injection of the piriformis muscle, as long as good education and training are provided to the operator. US has a number of advantages over traditional approaches, including accessibility and especially no ionizing radiation exposure for both health care providers and patients.

Subcutaneous and perineural botulinum toxin type a for neuropathic pain: a descriptive review.

OBJECTIVE: Botulinum toxin is a neurotoxin that has been widely used in chronic pain for the treatment of multiple conditions with a component of localized muscle spasm. Recent studies suggest that botulinum toxin is effective in the treatment of neuropathic pain syndromes such as postherpetic neuralgia or painful scars. METHODS: We searched the PubMed and OvidSP databases. We also included cross-referencing bibliographies from primary and review articles. DISCUSSION: In this descriptive review, we evaluate the usefulness, safety, and potential pathophysiological mechanism of botulinum toxin type A for treatment of painful disorders with neuropathic component such as postherpetic neuralgia, diabetic neuropathy, or trigeminal neuralgia. CONCLUSIONS: On the basis of the analysis of the reports published in the literature, it would seem that fractioned peripheral subcutaneous and perineural injections of botulinum toxin type A may be useful for the treatment of various chronic pain conditions with neuropathic component.

Subcutaneous botulinum toxin for chronic post-thoracotomy pain.

OBJECTIVE: Botulinum toxin is a neurotoxin that has been widely used in chronic pain for the treatment of multiple conditions with a component of localized muscle spasm. Recent studies suggest that botulinum toxin is effective in the treatment of neuropathic pain syndromes such as post-herpetic neuralgia. CASE REPORT: We report the case of a 67-year-old man who underwent atypical segmentectomy of a right lower lobe lung nodule. The patient was referred to our pain management department with a of 2-year history persistent pain along the thoracotomy scar having a predominantly neuropathic component, refractory to standard treatments. He was successfully treated with subcutaneous botulinum toxin type A. DISCUSSION: On the basics of our own experience and on the analysis of the reports published in the literature, fractioned subcutaneous injections of botulinum toxin may be useful for the treatment of various chronic localized pain conditions including chronic post-thoracotomy pain.

Spinal cord stimulation for the treatment of Buerger disease: a report on 3 cases.

OBJECTIVES: Buerger disease (or thromboangeiitis obliterans) is an inflammatory disease of the medium and small caliber arteries and veins that predominantly affects young males and presents with ischemia in the hands or the feet. It is closely associated with smoking. Critical ischemia of the lower limbs is a threat to the survival of the patient s extremities, and often disables its victims severely. This takes on an even greater significance in younger individuals who are still actively employed, as is the case in patients suffering from Buerger disease. Our aim was to evaluate the efficiency of the spinal cord stimulation as an alternative therapeutic option in acute stages of Buerger disease. RESULTS AND METHODS: We present a case series of males under the age of 45 years, diagnosed with thromboangeiitis obliterans and all of them were in the acute phase of the disease. They were satisfactorily treated with an implantable spinal cord stimulation device. DISCUSSION: Spinal cord stimulation is an accepted therapy for the treatment of chronic ischemic pain and ulcer healing and to avoid amputation in patients with severe, nonrevascularisable peripheral occlusive arteriopathy, and specially in the subgroup of patients with Buerger disease. It should not only be considered as a last resort strategy for pain control, but as a valid therapeutic option to improve perfusion of the limbs in the initial stages of the disease, however larger studies still remain necessary.

Use of a spinal cord stimulator for treatment of Martorell hypertensive ulcer.

Martorell ulcer is a specific disease entity characterized by multiple small homogeneous, symmetrical lesions, although single lesions are observed as well, most commonly located on the anterolateral aspect of the lower leg. The pain associated to these lesions is disproportionate to their size.Martorell ulcer designates a specific disease entity that occurs predominantly in middle-aged women with poorly controlled hypertension in the form of skin ulcers on the anterolateral aspect of the lower legs. The lesions initially appear as small, painful blisters which may or may not be associated with trauma. The pathophysiology of Martorell ulcer is assumed to be related to hypertension-induced arteriole changes in the dermis. The pain is often disproportionate, and the symptoms are not relieved by rest or elevation.Spinal cord stimulation (SCS) is an accepted evidence-based therapy for the treatment of chronic ischemic pain. Spinal cord stimulation is used as a therapeutic tool in the management of this disease not only for symptomatic pain control but also for accelerating the healing process through its effects on causal mechanisms. The beneficial effects of SCS when used to treat ischemic pain include pain relief, decreased infarction or ulcer size, decreased oxygen requirements, and increased claudication distance. Clinical and basic studies indicate that these beneficial effects are mainly associated with an increase or redistribution of blood flow to the ischemic area and/or normalization of the activity in the nervous system.We present the case of a 71-year-old woman diagnosed with Martorell ulcer in the acute phase of the disease. The patient was treated with SCS to achieve both pain relief and healing of the cutaneous ulcer.