Personality and psychiatric disorders in chronic pain male affected by erectile dysfunction: prospective and observational study.

The prevalence of personality disorders (PDs) and sexual dysfunction in chronic pain patients is higher than in general population. Our main objective was to analyse the influence of PD in patients with erectile dysfunction and chronic non-cancer pain and their response to andrological treatment. One-hundred one patients were included along 30 months. Pain intensity, quality of life, sexual life quality, anxiety and depression were analysed together with opioid dose. Erectile functioning was measured with the International Index of Erectile Function (IIEF) and PDs with Millon Clinical Multiaxial Inventory (MCMI-III). The mean age was 57 ± 12 years old, with moderate to severe pain, 70% were sexually active and presented moderate to severe ED. PDs were very frequent (31%, cut-off 85 and 84% cut-off 75 scores) mostly anxiety, compulsive, though disorder, somatoform and narcissistic. Self-defeating feature presence was significantly correlated (r = -0.4, 95% CI = -0.605 to -0.145, p = 0.002) with a more severe baseline ED and narcissistic, and a better response to andrological treatment (p = 0.010, d = 1.082). Patients with dysthymia features required significantly higher opioid doses vs. control (238 vs. 102 mg/day, respectively). These findings underline the importance of diagnosing PDs to rigorously treat patients with chronic pain and ED.

Lessons learned in attempting catheter-based interatrial electrical disconnection for nonpharmacologic rate control of atrial fibrillation or flutter.

PURPOSE: Ablation of atrioventricular (AV) conduction and pacemaker implantation is the therapy of last resort for symptomatic atrial tachyarrythmias when rhythm and rate control fail, but is far from ideal. To evaluate whether interatrial electrical disconnection as a result of catheter ablation is feasible and of potential clinical utility as a means of non-pharmacological heart rate control. METHODS: Eleven patients with medically refractory atrial fibrillation or left atrial flutter and symptomatic rapid ventricular response were included. The ablation strategy consisted primarily of right atrial ablation of the interatrial electrical connections, which were located by electroanatomical activation maps performed during coronary sinus stimulation. Successive activation maps were performed as each connection was blocked. If the procedure was considered unsuccessful AV nodal ablation was performed. RESULTS: The coronary sinus ostium was earliest in 10/11 and could be ablated in 5/10 patients. Interatrial conduction block was only achieved in one patient (9.1%). An unexpected AV nodal modulation with an increase in the Wenckebach cycle length (> 50 ms) occurred in 8/11 patients. These patients remained without pacemaker implantation and only 1/8 required AV nodal ablation during the 1-year follow-up. Quality of life questionnaires indicated significant improvement in patients with AV nodal modulation. CONCLUSION: Interatrial electrical disconnection by right atrial catheter ablation is a not feasible with present day technology. The extensive right atrial septal ablation performed resulted in significant AV nodal modulation in most patients, which persisted and resulted in improvement in quality of life.

Gender based differences, pharmacogenetics and adverse events in chronic pain management.

Safety data in chronic non-cancer pain (CNCP) with long-term opioid therapy has been poorly studied and can be differently influenced by gender. Furthermore, pharmacogenetics (PGx) could possibly be used to tailor pain medication based on the individual's genetic background. The aim was to assess whether PGx applied to a pharmacovigilance system could help to improve a patient's security profile. A pharmacovigilance data recording system was conducted over 24 months, including genotyping of OPRM1 variants (opioid receptor, A118G) and COMT (enzyme that degrades catecholamines such as norepinephrine, G1947A). Pain intensity (visual analogue scale, VAS), morphine equivalent daily dose (MEDD), adverse events (AEs) and suspected adverse drug reactions (ADRs) were recorded and analysed by gender. The Ethics Committee approved the study and data were analysed with R 3.6.0 software. A total of 748 patients were recruited in the study (67% female, VAS 62 ± 29 mm, MEDD 119 ± 114 mg/day) reporting a median of 6 (3.5-9) AEs/patient. Women presented more nausea, headaches, insomnia, loss of appetite, weight change, depression and dizziness than men. Analysis by genotype demonstrated that PGx influenced the prevalence of vomiting and depression in men, dizziness in women and sexual dysfunction in both. Physicians notified 150 ADRs mostly in females (79%) related to nervous system disorders. PGx applied to a pharmacovigilance recording system provides important information to achieve a better knowledge about AEs in CNCP pharmacological therapy. OPRM1 and COMT polymorphisms were associated with AEs in CNCP patients that differed according to gender.

OPRM1 Gene Interaction with Sleep in Chronic Pain Patients Treated with Opioids.

BACKGROUND: The experience of chronic non-cancer pain (CNCP) is one of the most common reasons individuals seek medical attention. Patients with CNCP frequently experience concomitant sleep-related problems. OBJECTIVES: The aim was to evaluate sleep problems in opioid naïve CNCP patients, before and after opioid titration, analyzing the influence of OPRM1 gene variants. STUDY DESIGN: A prospective, cohort, observational study. SETTING: This study was performed at the Pain Unit of the Alicante University General Hospital. METHODS: Pain and Medical Outcomes Study Sleep questionnaire (MOS-Sleep) were assessed at baseline and 3 months after opioid titration in 231 opioid naïve CNCP patients. Sleep data was compared with a matched-control group (n = 64). Morphine equivalent daily doses, adverse events, and drugs prescribed for pain were also registered. OPRM1 polymorphism rs1799971 was analyzed by RT-PCR. Ethics Committee approved the study and results were analyzed by R software. RESULTS: After 3 months of opioid titration, patients with CNCP (63 ± 14 years, 64% female, VAS 74 ± 17 mm) significantly decreased pain intensity, anxiety and depression, and increased quality of life. Sleep problems were significantly more frequent in females (P = 0.002). Age, quality of life, anxiety, and depression all influenced sleep disturbances and problems indices, which were significantly different from the control group. Furthermore, the OPRM1 118-GG genotype was also associated with significantly lower sleep adequacy, and more sleep problems. LIMITATIONS: Total number of subjects studied was relatively small and most patients were on other non-opioid centrally-acting medications. CONCLUSIONS: Opioids decreased CNCP severity, improving patients' psychological areas, and quality of life. However, patients with OPRM1 118-GG genotype indicated an increase in sleep problems and worsening sleep pattern while taking opioids. KEY WORDS: OPRM1, pharmacogenetics, MOS-Sleep, opioids, chronic noncancer pain, sleep related problems, sleep problem index SLP-6 and SLP-9.

Endothelial nitric oxide synthase gene polymorphisms and erectile dysfunction in chronic pain.

OBJECTIVES: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards. SUBJECT PATIENTS/METHODS: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software. RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients. CONCLUSION: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

Health benefits of an adverse events reporting system for chronic pain patients using long-term opioids.

BACKGROUND: Safety data from long-term opioid therapy in the real world has been poorly studied in chronic non-cancer pain (CNCP). The aim was to design a pharmacovigilance data recording system and assess whether participation in this recording system improves pain management, enhancing patient's health status. METHODS: A pharmacovigilance data recording system was conducted during 24 months. Data were self-reported by patients (pain, adverse events [AEs] and healthcare resources use) and physicians (morphine equivalent daily dose [MEDD] prescribed and suspected adverse drug reaction [ADRs]). Outcomes from patients with (case) or without (controls) suspected ADRs and cases follow-up were also compared with Spanish Pharmacovigilance System data. RESULTS: A total of 753 patients were recruited in 897 visits. Fentanyl and tramadol were the most prescribed opioids, 89% with concomitant drugs, pregabalin being the one with the most potential drug interactions. Cases presented significantly higher pain intensity (VAS 67 ± 26 vs 59 ± 30 mm, P < 0.05), number of AEs (8 ± 6 vs 5 ± 3 AEs/patient, P < 0.01), polypharmacy related to pain (65% vs 34%, P < 0.01) and MEDD (139 ± 130 vs 106 ± 99 mg/d, P < 0.01) than controls. Furthermore, cases presented significant higher changes in pharmacological pain therapy due to pain, unplanned emergency visits and hospital admission than controls. Physicians notified 168 suspected ADRs mostly related to neurological or psychiatric events and 8% of them were previously unknown. CONCLUSIONS: This data recording system provided important information to achieve a better control of CNCP pharmacological pain therapy, improving patient's health status and reducing costs to the Health System.

Endothelial nitric oxide synthase gene polymorphisms and erectile dysfunction in chronic pain.

OBJECTIVES: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards. SUBJECT PATIENTS/METHODS: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software. RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients. CONCLUSION: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

Randomized, Controlled, Crossover Study of Self-administered Jacobson Relaxation in Chronic, Nonspecific, Low-back Pain.

CONTEXT: Opioids decrease pain and improve functional capacity and quality of life; however, they are not always effective and are associated with harmful side effects. Few studies have shown that relaxation-based therapies, in comparison with usual care, can decrease pain. OBJECTIVE: The objective of the study was to investigate whether a controlled relaxation treatment, Jacobson progressive muscular relaxation (PMR), was effective in relieving chronic low-back pain (CLBP) and reducing pain comorbidities. The research team hypothesized that PMR-controlled relaxation could be more effective in reducing CLBP than music. DESIGN: The research team designed a randomized, controlled, crossover study. SETTING: The study took place in the pain unit, a clinic, in the Department of Health at Alicante-General Hospital (Alicante, Spain). PARTICIPANTS: Participants in this study were 58 adults with nononcological CLBP, secondary to lumbar canal stenosis, who had been treated with opioids without any changes in the 3 mo prior to the study. INTERVENTION: Participants were randomly assigned to 1 of 2 groups, each of which received 2 treatments, but in a different order (ie, either AB or BA where A was the standardized PMR, the intervention, and B was relaxing music, the control. For both groups, the 2 treatment periods were 8 wk in length, with a 1-mo washout period between them. OUTCOME MEASURES: The primary outcome measures included (1) a visual analogue scale-pain and relief intensity; (2) the 12-item short form health survey-quality of life; (3) the hospital anxiety and depression scale-anxiety and depression; and (4) the medical outcomes study sleep scale-sleep disturbances. Secondary outcome measures included a self-efficacy scale and a measure of satisfaction with treatment and compliance. RESULTS: Pain was mostly mild to moderate. Greater decreases in pain between baseline and postintervention were observed for the PMR vs the control treatment in the mild pain category, with a VAS difference of 1.8 cm and P = .018. Significant differences were also found in anxiety, depression, quality of life, and sleep between participants in the 3 pain categories. Self-rated adherence was high. CONCLUSIONS: Findings support the efficacy and acceptability of a self-guided PMR intervention for reducing CLBP with minimal time with a therapist.

Disfunción eréctil en pacientes con dolor crónico tratados con opioides / Erectile dysfunction in patients with chronic pain treated with opioids

Introducción y objetivo: El dolor crónico asocia comorbilidades que condicionan la calidad de vida de los pacientes y que afectan, entre otros, a su esfera sexual. Dentro de los efectos secundarios de los analgésicos opioides destaca la disfunción eréctil (DE) debida en parte a la inhibición del eje gonadal-hipofisario-hipotalámico y al descenso de los niveles de testosterona. Evaluar la DE y la efectividad de su tratamiento en varones con dolor crónico tratados a largo plazo con opioides es el objetivo. Material y métodos: Estudio observacional prospectivo de 3 años de duración, donde se evalúa la intensidad del dolor (escala visual analógica, 0-10cm), función eréctil (IIEF-FE, rango 1-30 puntos), calidad de vida (EVA-EQ, 0-100mm), calidad de vida sexual (mSLQ-QOL, 0-100 puntos), ansiedad/depresión (HAD, 0-21 puntos) y niveles de testosterona en pacientes que refirieron disfunción sexual (De y/o disminución de la libido). Se realizó un seguimiento de 6 meses, a cada paciente incluido, tras el tratamiento habitual en la Unidad de Andrología, valorando su respuesta con la escala de Impresión Clínica Global del Cambio (ICG-C). El estudio fue aprobado por el Comité Ético de Investigación Clínica y los datos fueron analizados estadísticamente con GraphPad Prism 5. Resultados: Se encontró una prevalencia de DE en el 27,6% (n=105; 57±12,2 años; dosis media equivalente de morfina de 107,1±107,9mg/día; 84,3% fármacos coadyuvantes). Un 42% presentó mejoría significativa a los 6 meses tras ser tratados con iPDE5 (48,5%) y/o con testosterona en gel (81,8%), con resolución de la DE en el 31% (p=0,000). Se observó una correlación positiva entre el IIEF y una mejora significativa de su calidad de vida sexual (55,5±25,7 puntos; p=0,000) y de su ansiedad (7,4±4,3 puntos; p=0,048). No se observaron cambios significativos en los niveles de testosterona, en la intensidad del dolor o calidad de vida, que se mantuvieron moderados. Conclusiones: La función eréctil y la calidad de vida sexual en pacientes tratados crónicamente con opioides mejoran, junto con la ansiedad, tras su tratamiento andrológico. El abordaje de los pacientes con dolor debe incluir la historia clínica sexual por el importante impacto emocional que supone para el paciente, por el impacto sobre su calidad de vida global y por su buena respuesta clínica al tratamiento interdisciplinar (AU)

Introduction and objective: Chronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal-pituitary-hypothalamic axis and the decline in testosterone levels. To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. Material and methods: Prospective observational study lasting 3 years, where the intensity of pain (visual analogue scale, 0-10cm), erectile function (IIEF-EF, range 1-30 points), quality of life (EQ-VAS, 0-100mm), quality of sexual life (MSLQ-QOL, 0-100 points), anxiety/depression (HAD, 0-21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. Results: ED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. Conclusions: Erectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the significant emotional impact posed to the patient, the impact on their overall quality of life and its good clinical response to an interdisciplinary treatment (AU)

Erectile dysfunction in patients with chronic pain treated with opioids. / Disfunción eréctil en pacientes con dolor crónico tratados con opioides.

INTRODUCTION AND OBJECTIVE: Chronic pain is associated with comorbidities that have an impact on the quality of life of patients and, among others, affect their sexual functioning. One of the most relevant side effects of opioid analgesics is erectile dysfunction (ED), due in part to the inhibition of the gonadal-pituitary-hypothalamic axis and the decline in testosterone levels. To evaluate ED and effectiveness of treatment in men with chronic pain treated with long-term opioids. MATERIAL AND METHODS: Prospective observational study lasting 3 years, where the intensity of pain (visual analogue scale, 0-10cm), erectile function (IIEF-EF, range 1-30 points), quality of life (EQ-VAS, 0-100mm), quality of sexual life (MSLQ-QOL, 0-100 points), anxiety/depression (HAD, 0-21 points) and testosterone levels, was assessed in patients who reported sexual dysfunction (ED or libido modification). A 6-month follow-up was applied to each patient after administering the usual treatment in the Andrology Unit. The study was approved by the Clinical Research Ethics Committee and data were statistically analyzed with the GraphPad Prism 5 software. RESULTS: ED was observed in 27.6% of patients (n=105, 57±12.2 years, mean dose of morphine equivalent=107.1±107.9mg/day, 84.3% adjuvant analgesics). After 6 months, 42% of patients showed a significant improvement after being treated with iPDE5 (48.5%) and/or testosterone gel (81.8%), with a resolution rate of 31% (p=0.000). A positive correlation was observed between the improvement of IIEF and quality of sexual life (55.5±25.7 points, p=0.000), as well as anxiety (7.4±4.3 points, p=0.048). No significant changes were observed in the levels of testosterone, in the levels of pain nor in the quality of life, which remained moderate. CONCLUSIONS: Erectile function and quality of sexual life, as well as anxiety, improved in patients treated chronically with opioids after administering andrological treatment. The management of patients with pain should include a review of their sexual health history given the significant emotional impact posed to the patient, the impact on their overall quality of life and its good clinical response to an interdisciplinary treatment.

The relationship of salivary testosterone and male sexual dysfunction in opioid-associated androgen deficiency (OPIAD).

BACKGROUND: Opioids are an effective treatment for chronic non-malignant pain (CNP). Long-term use risks and side effects such as opioid-induced androgen deficiency (OPIAD) exist. This could be measured by saliva testosterone (Sal-T). OBJECTIVES: To evaluate OPIAD in long-term opioid use in CNP patients. METHODS: A cross-sectional study included CNP male outpatients under opioid treatment. Total-Testosterone (Total-T), Free-Testosterone (Free-T), Bio-Testosterone (Bio-T) and Sal-T were measured. Correlations were calculated by Spearman's rho (SPSS 20). RESULTS: From 2012 to 2014, 134 from 249 (54%) consecutive male outpatients reported erectile dysfunction (ED), 37% of them related to opioids and 19% evidenced OPIAD. A total of 120 subjects (94 cases and 26 matched-controls) were included. A significantly lower luteinizing hormone, Total-T and Free-T were found, as well as, a significant correlation between Sal-T and Total-T (r = 0.234, p = 0.039), Bio-T (r = 0.241, p = 0.039), IIEF (r = 0.363, p = 0.003) and HAD-anxiety (r = -0.414, p = 0.012) in OPIAD patients. Sal-T levels were significantly lower in patients with severe-moderate ED versus mild ED (p = 0.045) and in patients with severe ED versus moderate-mild ED (p = 0.036). CONCLUSIONS: These data demonstrate the high prevalence of ED in long-term use of opioids, part of this is associated to OPIAD, which can be tested by Sal-T as a non-invasive approach.

Opioids Increase Sexual Dysfunction in Patients With Non-Cancer Pain.

INTRODUCTION: Long-term opioid therapy has been found to have a strong impact on the hypothalamic-pituitary-gonadal axis that can be manifested clinically by sexual dysfunction (SD). This event is rarely reported and thus unnoticed and undertreated. AIM: To analyze the presence of SD in a large group of patients receiving long-term opioids. METHODS: A descriptive, cross-sectional pilot study of sexual health was conducted for 2 years in 750 consecutive ambulatory patients with chronic non-cancer pain (CNP) receiving opioids for at least 12 months. Cases that reported SD and matched controls were included. Standardized questionnaires and medical record reviews were used to assess rates of pain at diagnosis, daily morphine equivalent doses, and opioid adverse effects. MAIN OUTCOME MEASURES: Sexual function was determined by the Female Sexual Function Index (FSFI; scores = 2-36) and the International Index of Erectile Function erectile function domain (IIEF-EF; scores = 1-30). RESULTS: Thirty-three percent of 33% of 750 patients with CNP recorded SD based on their spontaneous notification at the pain unit. Men reported SD significantly more frequently than women (33% vs 25%, respectively, P < .05), although they reported having a regular partner (84% vs 70%, P = .03) and a sexually active life (69% vs 34%, respectively, P = .00) significantly more often. FSFI scores were significantly influenced by sexual activity in lubrication and arousal. IIEF scores were significantly determined by age in satisfaction with sexual intercourse and overall satisfaction. The morphine equivalent dose was significant higher in men than in women (38%; median = 70 mg/d, interquartile range = 43.1-170, 115.5 ± 110.3 mg/d vs median = 60 mg/d, interquartile range = 30-100.6, 76.67 ± 63.79 mg/d, P = .016) at the same mean intensity of pain (P = .54), which correlated to FSFI scores (r = -0.313, P = .01). CONCLUSION: SD is prevalent in patients with CNP and higher in men who received a significantly higher mean opioid dose at the same intensity pain level than women. The morphine equivalent dose was correlated to SD intensity. Evidence-based interventions to support sexual activity and function in CNP are needed.