Developmental Fluoxetine Exposure Normalizes the Long-Term Effects of Maternal Stress on Post-Operative Pain in Sprague-Dawley Rat Offspring

Early life events can significantly alter the development of the nociceptive circuit. In fact, clinical work has shown that maternal adversity, in the form of depression, and concomitant selective serotonin reuptake inhibitor (SSRI) treatment influence nociception in infants. The combined effects of maternal adversity and SSRI exposure on offspring nociception may be due to their effects on the developing hypothalamic-pituitary-adrenal (HPA) system. Therefore, the present study investigated long-term effects of maternal adversity and/or SSRI medication use on nociception of adult Sprague-Dawley rat offspring, taking into account involvement of the HPA system. Dams were subject to stress during gestation and were treated with fluoxetine (2×/5 mg/kg/day) prior to parturition and throughout lactation. Four groups of adult male offspring were used: 1. Control+Vehicle, 2. Control+Fluoxetine, 3. Prenatal Stress+Vehicle, 4. Prenatal Stress+Fluoxetine. Results show that post-operative pain, measured as hypersensitivity to mechanical stimuli after hind paw incision, was decreased in adult offspring subject to prenatal stress alone and increased in offspring developmentally exposed to fluoxetine alone. Moreover, post-operative pain was normalized in prenatally stressed offspring exposed to fluoxetine. This was paralleled by a decrease in corticosteroid binding globulin (CBG) levels in prenatally stressed offspring and a normalization of serum CBG levels in prenatally stressed offspring developmentally exposed to fluoxetine. Thus, developmental fluoxetine exposure normalizes the long-term effects of maternal adversity on post-operative pain in offspring and these effects may be due, in part, to the involvement of the HPA system

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

BACKGROUND: Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis. METHODS: We performed an RF-DRG procedure in 17 consecutive CP patients with severe hip flexor/adductor spasms accompanied by pain or care-giving difficulties. Six children were systematically evaluated at baseline, and 1 month and 6 months after treatment by means of the Modified Ashworth Scale (MAS), Gross Motor Function Measure (GMFM) and a self-made caregiver's questionnaire. Eleven subsequent children were evaluated using a Visual Analogue Scale (VAS) for spasticity, pain and ease of care. RESULTS: A total of 19 RF-DRG treatments were performed in 17 patients. We found a small improvement in muscle tone measured by MAS, but no effect on the GMFM scale. Despite this, the caregivers of these six treated children unanimously stated that the quality of life of their children had indeed improved after the RF-DRG. In the subsequent 11 children we found improvements in all VAS scores, in a range comparable to the conventional treatment options. CONCLUSION: RF-DRG is a promising new treatment option for severe spasticity in CP patients, and its definitive effectiveness remains to be defined in a randomised controlled trial

Randomised controlled trial of cervical radiofrequency lesions as a treatment for cervicogenic headache [ISRCTN07444684]

BACKGROUND: Cervicogenic headache (CEH) is a unilateral headache localised in the neck or occipital region, projecting to the frontal and temporal regions. Since the pathogenesis of this syndrome appears to have an anatomical basis in the cervical region, several surgical procedures aimed at reducing the nociceptive input on the cervical level, have been tested. We developed a sequence of various cervical radiofrequency neurotomies (facet joint denervations eventually followed by upper dorsal root ganglion neurotomies) that proved successful in a prospective pilot trial with 15 CEH patients. To further evaluate this sequential treatment program we conducted a randomised controlled trial METHODS: 30 patients with cervicogenic headache according to the Sjaastad diagnostic criteria, were randomised. 15 patients received a sequence of radiofrequency treatments (cervical facet joint denervation, followed by cervical dorsal root ganglion lesions when necessary), and the other 15 patients underwent local injections with steroid and anaesthetic at the greater occipital nerve, followed by transcutaneous electrical nerve stimulation (TENS) when necessary. Visual analogue scores for pain, global perceived effects scores, quality of life scores were assessed at 8, 16, 24 and 48 weeks. Patients also kept a headache diary. RESULTS: There were no statistically significant differences between the two treatment groups at any time point in the trial. CONCLUSION: We did not find evidence that radiofrequency treatment of cervical facet joints and upper dorsal root ganglions is a better treatment than the infiltration of the greater occipital nerve, followed by TENS for patients fulfilling the clinical criteria of cervicogenic headache

Radiofrequency Treatment of Facet-related Pain: Evidence and Controversies

Pain originating from the lumbar facet joints is estimated to represent about 15% of all low back pain complaints. The diagnostic block is considered to be a valuable tool for confirming facetogenic pain. It was demonstrated that a block of the ramus medialis of the ramus dorsalis is preferred over an intra-articular injection. The outcome of the consequent radiofrequency treatment is not different in patients reporting over 80% pain relief after the diagnostic block than in those who have between 50% and 79% pain relief. There is one well-conducted comparative trial assessing the value of one or two controlled diagnostic blocks to none. The results of the seven randomized trials on the use of radiofrequency treatment of facet joint pain demonstrate that good patient selection is imperative for good clinical outcome. Therefore, we suggest one block of the ramus medialis of the ramus dorsalis before radiofrequency treatment

Feasibility of a mobile and web-based intervention to support self-management in outpatients with cancer pain

Purpose: Cancer pain is a prevalent and distressing symptom. To enhance self-management in outpatients, a multi-component intervention was developed, integrating patient self-management and professional care through healthcare technology. This article describes feasibility of the intervention in everyday practice. Method: Patients with moderate to severe cancer pain (n = 11) and registered nurses specialized in pain and palliative care (n = 3) participated in a four-week study. The intervention involved daily monitoring, graphical feedback, education, and advice by means of a mobile application for patients and a web application for nurses. Learnability, usability and desirability were measured in patients with a 20-item questionnaire (1–5 scale), higher scores indicating better feasibility. Patients' adherence was based on completion rates from server logs. Single semi-structured interviews with patients and a focus group interview with nurses provided insight into experiences. Results: Questionnaire findings confirmed learnability (4.8), usability (4.8) and desirability (4.6) of the application for patients. Average completion rates were 76.8% for pain monitoring, 50.4% for medication monitoring and 100% for education sessions. Interviews revealed that patients were pleased with the simplicity of the mobile application and appreciated different components. Nurses agreed upon the added value and were mostly positive about the possibilities of the web application. Patients and nurses provided ideas for improvements relating to the content and technical performance of the intervention. Conclusions: Study results demonstrate feasibility of the intervention in everyday practice. Provided that content-related and technical adjustments are made, the intervention enables patients with cancer pain to practice self-management and nurses to remotely support these patients

Self-management support intervention to control cancer pain in the outpatient setting: a randomized controlled trial study protocol

Background: Pain is a prevalent and distressing symptom in patients with cancer, having an enormous impact on functioning and quality of life. Fragmentation of care, inadequate pain communication, and reluctance towards pain medication contribute to difficulties in optimizing outcomes. Integration of patient self-management and professional care by means of healthcare technology provides new opportunities in the outpatient setting. Methods/Design: This study protocol outlines a two-armed multicenter randomized controlled trial that compares a technology based multicomponent self-management support intervention with care as usual and includes an effect, economic and process evaluation. Patients will be recruited consecutively via the outpatient oncology clinics and inpatient oncology wards of one academic hospital and one regional hospital in the south of the Netherlands. Irrespective of the stage of disease, patients are eligible when they are diagnosed with cancer and have uncontrolled moderate to severe cancer (treatment) related pain defined as NRS ≥ 4 for more than two weeks. Randomization (1:1) will assign patients to either the intervention or control group; patients in the intervention group receive self-management support and patients in the control group receive care as usual. The intervention will be delivered by registered nurses specialized in pain and palliative care. Important components include monitoring of pain, adverse effects and medication as well as graphical feedback, education, and nurse support. Effect measurements for both groups will be carried out with questionnaires at baseline (T0), after 4 weeks (T1) and after 12 weeks (T2). Pain intensity and quality of life are the primary outcomes. Secondary outcomes include self-efficacy, knowledge, anxiety, depression and pain medication use. The final questionnaire contains also questions for the economic evaluation that includes both cost-effectiveness and cost-utility analysis. Data for the process evaluation will be gathered continuously over the study period and focus on recruitment, reach, dose delivered and dose received. Discussion: The proposed study will provide insight into the effectiveness of the self-management support intervention delivered by nurses to outpatients with uncontrolled cancer pain. Study findings will be used to empower patients and health professionals to improve cancer pain control. Trial registration: NCT02333968 December 29, 201

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting