Brain Dopamine and Serotonin Receptors in the Perception of Pain. Positron Emission Tomography Studies in Healthy Subjects

The role of dopamine and serotonin in spinal pain regulation is well established. However, little is known concerning the role of brain dopamine and serotonin in the perception of pain in humans. The aim of this study was to assess the potential role of brain dopamine and serotonin in determining experimental pain sensitivity in humans using positron emission tomography (PET) and psychophysical methods. A total of 39 healthy subjects participated in the study, and PET imaging was performed to assess brain dopamine D2/D3 and serotonin 5-HT_1A receptor availability. In a separate session, sensitivity to pain and touch was assessed with traditional psychophysical methods, allowing the evaluation of potential associations between D2/D3 and 5-HT_1A binding and psychophysical responses. The subjects’ responses were also analyzed according to Signal Detection Theory, which enables separate assessment of the subject’s discriminative capacity (sensory factor) and response criterion (non-sensory factor). The study found that the D2/D3 receptor binding in the right putamen was inversely correlated with pain threshold and response criterion. 5-HT_1A binding in cingulate cortex, inferior temporal gyrus and medial prefrontal cortex was inversely correlated with discriminative capacity for touch. Additionally, the response criterion for pain and intensity rating of suprathreshold pain were inversely correlated with 5-HT_1A binding in multiple brain areas. The results suggest that brain D2/D3 receptors and 5-HT_1A receptors modulate sensitivity to pain and that the pain modulatory effects may, at least partly, be attributed to influences on the response criterion. 5-HT_1A receptors are also involved in the regulation of touch by having an effect on discriminative capacity.

Parents as Pain Killers in the Pain Management of Preterm Infants

Vanhemmat keskoslasten kivun lievittäjinä Tutkimuksen tarkoituksena oli kehittää uusi kivunlievitysmenetelmä, Vanhempien käsikapalo, keskoslasten kivunhoitoon vastasyntyneiden teho-osastolla. Vanhempien käsikapalon tehokkuutta verrattiin kahdessa satunnaistetussa kontrolloidussa crossover-tutkimusasetelmassa ei-lääkkeelliseen näyttöön perustuvaan hoitoon (P.O. glukoosiliuos), lääkkeelliseen menetelmään (I.V. oksikodoni) ja lumeeseen (P.O. vesi) tai kontrolli hoitoon kantapääpiston ja hengitysteiden imemisen aikana. Lisäksi mitattiin kivunhoidon lyhytaikaisia sivuvaikutuksia (hapetuksen- ja pulssinlasku) ja pidempiaikaisia vaikutuksia uneen. Tutkittujen lasten ikä oli 28 raskausviikkoa (n = 20) ja 28 1/7 (n = 20). Toimenpidekipua arvioitiin Premature Infant Pain Profile (PIPP) -kipumittarilla. Interventioiden jälkeen unen rakenne analysoitiin 13 tunnin polysomnografia-rekisteröinneistä. Viimeisessä vaiheessa haastateltiin äitejä (n = 23), jotka olivat käyttäneet vanhempien käsikapaloa 2–4 viikkoa vastasyntyneiden teho-osastolla, strukturoidulla the Clinical Interview for Parents of High-Risk Infants -haastattelulla, johon oli lisätty kysymyksiä lapsen kivunhoidosta. Kantapääpiston aikana PIPP–pisteet olivat merkitsevästi matalampia P.O. glukoosiliuoksella (ka 4,85 ± 1,73, p ≤ 0,001) ja vanhempien käsikapalolla (ka 5,20 ± 1,70, p = 0,004) verrattuna lumeeseen (ka 7,05 ± 2,16). Hengitysteiden imemisen yhteydessä PIPP–pisteet olivat matalampia P.O. glukoosiliuoksella (ka 11,05 ± 2,31, p = 0,014) ja vanhempien käsikapalolla (ka 11,25 ± 2,47, p = 0,034) verrattuna lumeeseen (ka 12,40 ± 2,06). Oksikodonin teho oli verrattavissa lumeeseen kummankin toimenpiteen aikana. P.O. glukoosiliuoksen (21,3 %) ja lumeen (12,5 %) annosteluun liittyi merkittävästi enemmän lyhytaikaisia sivuvaikutuksia verrattuna oksikodoniin (5 %) tai vanhempien käsikapaloon (5 %). Oksikodoni muutti keskoslasten unen rakennetta vähentämällä merkittävästi aktiivisen unen määrää verrattuna muihin hoitoihin. Vanhemmat suhtautuivat positiivisesti käsikapalon käyttöön. Äitien osallistuminen kivunhoitoon voitiin jaotella kolmeen eri tyylin, jotka selittyivät äidin kiintymyksen tunteilla ja lapsen tehohoitoon liittyvällä stressillä. Vanhempien käsikapalo on suositeltavampi lyhyen toimenpidekivun lievittäjä kuin P.O. glukoosiliuos tai I.V. oksikodoni, kun tehokkuus, turvallisuus ja perhe otetaan huomioon.

Classification, comorbidity, heredity, and risk factors of female sexual dysfunctions

Female sexual dysfunctions, including desire, arousal, orgasm and pain problems, have been shown to be highly prevalent among women around the world. The etiology of these dysfunctions is unclear but associations with health, age, psychological problems, and relationship factors have been identified. Genetic effects explain individual variation in orgasm function to some extent but until now quantitative behavior genetic analyses have not been applied to other sexual functions. In addition, behavior genetics can be applied to exploring the cause of any observed comorbidity between the dysfunctions. Discovering more about the etiology of the dysfunctions may further improve the classification systems which are currently under intense debate. The aims of the present thesis were to evaluate the psychometric properties of a Finnish-language version of a commonly used questionnaire for measuring female sexual function, the Female Sexual Function Index (FSFI), in order to investigate prevalence, comorbidity, and classification, and to explore the balance of genetic and environmental factors in the etiology as well as the associations of a number of biopsychosocial factors with female sexual functions. Female sexual functions were studied through survey methods in a population based sample of Finnish twins and their female siblings. There were two waves of data collection. The first data collection targeted 5,000 female twins aged 33–43 years and the second 7,680 female twins aged 18–33 and their over 18–year-old female siblings (n = 3,983). There was no overlap between the data collections. The combined overall response rate for both data collections was 53% (n = 8,868), with a better response rate in the second (57%) compared to the first (45%). In order to measure female sexual function, the FSFI was used. It includes 19 items which measure female sexual function during the previous four weeks in six subdomains; desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain. In line with earlier research in clinical populations, a six factor solution of the Finnish-language version of the FSFI received supported. The internal consistencies of the scales were good to excellent. Some questions about how to avoid overestimating the prevalence of extreme dysfunctions due to women being allocated the score of zero if they had had no sexual activity during the preceding four weeks were raised. The prevalence of female sexual dysfunctions per se ranged from 11% for lubrication dysfunction to 55% for desire dysfunction. The prevalence rates for sexual dysfunction with concomitant sexual distress, in other words, sexual disorders were notably lower ranging from 7% for lubrication disorder to 23% for desire disorder. The comorbidity between the dysfunctions was substantial most notably between arousal and lubrication dysfunction even if these two dysfunctions showed distinct patterns of associations with the other dysfunctions. Genetic influences on individual variation in the six subdomains of FSFI were modest but significant ranging from 3–11% for additive genetic effects and 5–18% for nonadditive genetic effects. The rest of the variation in sexual functions was explained by nonshared environmental influences. A correlated factor model, including additive and nonadditive genetic effects and nonshared environmental effects had the best fit. All in all, every correlation between the genetic factors was significant except between lubrication and pain. All correlations between the nonshared environment factors were significant showing that there is a substantial overlap in genetic and nonshared environmental influences between the dysfunctions. In general, psychological problems, poor satisfaction with the relationship, sexual distress, and poor partner compatibility were associated with more sexual dysfunctions. Age was confounded with relationship length but had over and above relationship length a negative effect on desire and sexual satisfaction and a positive effect on orgasm and pain functions. Alcohol consumption in general was associated with better desire, arousal, lubrication, and orgasm function. Women pregnant with their first child had fewer pain problems than nulliparous nonpregnant women. Multiparous pregnant women had more orgasm problems compared to multiparous nonpregnant women. Having children was associated with less orgasm and pain problems. The conclusions were that desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain are separate entities that have distinct associations with a number of different biopsychosocial factors. However, there is also considerable comorbidity between the dysfunctions which are explained by overlap in additive genetic, nonadditive genetic and nonshared environmental influences. Sexual dysfunctions are highly prevalent and are not always associated with sexual distress and this relationship might be moderated by a good relationship and compatibility with partner. Regarding classification, the results supports separate diagnoses for subjective arousal and genital arousal as well as the inclusion of pain under sexual dysfunctions.

A Comparative Study of the Effectiveness of a Prefabricated Appliance and a Stabilization Appliance in the Treatment of Myofascial pain and Headache

The aim of this thesis was to evaluate the short- and long-term effectiveness of a prefabricated occlusal appliance (R) on patients with myofascial pain and headache by comparing it with the treatment of the stabilization appliance (S). Another aim was to evaluate the effect of appliance treatment on stress-related salivary parameters like cortisol and IgA, as well as on flow rate values in these patients. Sixty-five patients diagnosed with myofascial temporomandibular disorder (TMD) pain, of whom 94% suffered concomitantly from headache, at two centres for Stomatognathic Physiology, one in Sweden and one in Finland, were included in this randomized controlled trial using Research Diagnostic Criteria for TMD (RDC/TMD), with history questionnaires and clinical examinations performed at baseline and at 6- and 10-weeks, and 6- and 12-month follow-ups. Patients were randomly assigned either to the R or the S group. Treatment outcome was measured according to IMMPACT (Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials), i.e. four chronic pain outcome domains: pain intensity, overall improvement, physical and emotional functioning. Changes in frequency and intensity of headache were recorded. Thirty-nine patients participated in the saliva study. Salivary analyses were performed at 6 and 10 weeks. The results revealed no differences between groups at baseline. At all follow-ups, all four outcome measures, as well as frequency and intensity of headache, showed statistically significant within-group improvement compared to baseline, without significant differences between groups. No treatment-induced changes in saliva parameters could be registered. In conclusion, the effectiveness of the prefabricated appliance seemed to be similar to that of the stabilization appliance in alleviating myofascial pain, and frequency and intensity of headache, in the short as well as the long term. However, no changes in salivary parameters were observed during treatment.

Safety and tolerability of controlled-release oxycodone on postoperative pain in patients submitted to the oncologic head and neck surgery

Objective: To evaluate the safety and tolerability of controlled-release oxycodone in the treatment of postoperative pain of head and neck oncologic resections.Methods: We conducted a prospective, observational and open study, with 83 patients with moderate to severe pain after head and neck oncological operations. All patients received general anesthesia with propofol, fentanyl and sevoflurane. Postoperatively, should they have moderate or severe pain, we began controlled-release oxycodone 20 mg 12/12 b.i.d on the first day and 10 mg b.i.d. on the second. We assessed the frequency and intensity of adverse effects, the intensity of postoperative pain by a verbal numeric scale and the use of rescue analgesia from 12 hours after administration of the drug and between 7 and 13 days after the last oxycodone dose.Results: The most common adverse events were nausea, vomiting, dizziness, pruritus, insomnia, constipation and urinary retention, most mild. No serious adverse events occurred. In less than 12 hours after the use of oxycodone, there was a significant decrease in the intensity of postoperative pain, which remained until the end of the study. The rescue medication was requested at a higher frequency when the opioid dose was reduced, or after its suspension.Conclusion: Controlled release oxycodone showed to be safe and well tolerated and caused a significant decrease in post-operative pain.

Validação do questionário de qualidade de vida (King's Health Questionnaire) em mulheres brasileiras com incontinência urinária

OBJETIVO: a proposta deste estudo foi traduzir e validar o King's Health Questionnaire (KHQ) para mulheres brasileiras com incontinência urinária. MÉTODOS: 134 pacientes com incontinência urinária, confirmada pelo estudo urodinâmico, foram recrutadas em ambulatório de Uroginecologia. Inicialmente, traduzimos o questionário KHQ para a língua portuguesa (do Brasil) de acordo com critérios internacionais. Devido às diferenças da língua, fizemos a adaptação cultural, estrutural, conceitual e semântica do KHQ, para que as pacientes compreendessem as questões. Todas as pacientes responderam duas vezes o KHQ, no mesmo dia, com dois entrevistadores distintos, com intervalo de 30 minutos de uma entrevista para a outra. Depois de 7 a 14 dias, a aplicação do questionário foi repetida numa segunda visita. Foram testadas a confiabilidade (consistência interna intra e inter-observador) e validade do constructo e discriminativa. RESULTADOS: foram necessárias várias adaptações culturais até obtermos a versão final. A consistência interna intra-observador (alfa de Cronbach) das diversas dimensões oscilou de moderada a alta (0,77-0,90) e a consistência interna inter-observador oscilou de 0,66 a 0,94. Na validação do constructo, obtivemos correlação de moderada a forte entre os domínios específicos para incontinência urinária e manifestações clínicas que, sabidamente, afetam a qualidade de vida dessas pacientes. CONCLUSÃO: o KHQ foi adaptado ao idioma português e para a cultura brasileira, mostrando grande confiabilidade e validade, devendo ser incluído e utilizado em qualquer estudo brasileiro de incontinência urinária.

Validação de versão para o português de questionário sobre qualidade de vida para mulher com endometriose (Endometriosis Health Profile Questionnaire - EHP-30)

OBJETIVO: desenvolvimento da versão em português brasileiro do Endometriosis Health Profile Questionnaire (EHP-30), adaptação transcultural ao Brasil e avaliação das medidas psicométricas do EHP-30 Português em amostra brasileira. MÉTODOS: o instrumento original em inglês foi vertido para o português, seguindo diretrizes internacionais, passando por todas as etapas de tradução, retrotradução e comparação das versões para adaptação transcultural, validade de face e de conteúdo. O EHP-30 Português foi aplicado a uma amostra de 54 pacientes com diagnóstico de endometriose para análise de consistência interna, usando o alfa de Cronbach. A fidedignidade teste-reteste foi avaliada pelo coeficiente de correlação intraclasse (ICC). Para a avaliação de validade de construto convergente foi testada correlação entre o EHP-30 Português, WHOQOL-Bref e o Inventário de Depressão de Beck (BDI). RESULTADOS: a avaliação da consistência interna apresentou valores de α=0,8 a 0,9, sugerindo homogeneidade entre as questões. A fidedignidade teste-reteste apresentou ICC de 0,8 a 0,9, demonstrando estabilidade do instrumento. Na validação de construto, demonstraram-se fortes correlações da escala de auto-imagem do EHP-30 com os domínios físico (-0,6) e psicológico (-0,6) do WHOQOL-Bref e da escala de suporte social com o BDI (0,5), evidenciando-se, assim, boa correlação com outros instrumentos de avaliação de qualidade de vida. CONCLUSÕES: o EHP-30 Português mostrou ser um instrumento de fácil e rápida aplicação e bem aceito pelas pacientes, apresentando bom desempenho psicométrico, com medidas de fidedignidade adequadas (consistência interna e fidedignidade teste-reteste) e validade de construto. Estes resultados demonstram que o EHP-30 Português é um instrumento adequado para avaliação de qualidade de vida em mulheres brasileiras com endometriose em ambiente clínico e de pesquisa.

Adaptação sociocultural do short personal experiences questionnaire (SPEQ) no Brasil

OBJETIVO: traduzir e adaptar culturalmente o Short Personal Experiences Questionnaire (SPEQ) para a língua portuguesa, no Brasil, em mulheres climatéricas. MÉTODOS: a versão original do questionário, em inglês, proveniente da Universidade de Melbourne (Austrália), inicialmente foi traduzida para a língua portuguesa e retraduzida ao inglês. Procedeu-se, então, à adaptação sociocultural do vocabulário e da construção linguística para melhor compreensão. O questionário foi então aplicado para pré-teste em 50 mulheres, em etapas sucessivas, até que não houvesse mais dúvidas. A versão final do instrumento adaptado foi utilizada em estudo de base populacional, autorrespondido anonimamente por 378 mulheres pesquisadas, entre 40 e 65 anos e com 11 anos ou mais de escolaridade, nascidas no Brasil. Foi aplicada uma análise de confiabilidade (consistência interna, pelo alfa de Cronbach), uma análise de validade do construto (correlação de pares de itens que compõem o SPEQ e cada um destes com os quatro fatores obtidos e com o escore total), e uma análise de validade de critério (correlação entre os quatro fatores obtidos com o escore de classificação geral da vida sexual). RESULTADOS: cento e oitenta mulheres responderam a todas as perguntas do SPEQ e foram incluídas na análise. A consistência interna (alfa de Cronbach) para os nove itens do SPEQ situou-se entre 0,55 e 0,77 e o alfa geral foi 0,68. Na análise de validade do construto, a maioria dos coeficientes de correlação se mostrou significativo (valores p<0,005). A análise de validade de critério mostrou coeficientes de correlação significativos em sua maior parte. CONCLUSÕES: a versão em português do instrumento SPEQ, após processo de adaptação, mostrou-se útil e adequada para levantar informações relativas à função sexual e dispareunia em mulheres brasileiras entre 40 e 65 anos e com 11 anos ou mais de escolaridade.

Validação do International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) para a língua portuguesa

OBJETIVOS: traduzir, adaptar culturalmente e validar o questionário International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) para a língua portuguesa. MÉTODOS: dois tradutores brasileiros, cientes dos objetivos da pesquisa, traduziram o ICIQ-OAB para o português e as duas traduções geradas foram retrotraduzidas por outros dois tradutores ingleses. As diferenças entre as versões foram harmonizadas e pré-testadas em um estudo piloto. A versão final do ICIQ-OAB foi aplicada junto com a versão já traduzida e validada do questionário International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF) em 142 pacientes, entre homens e mulheres, com sintomas miccionais irritativos. Para validação do ICIQ-OAB foram testadas propriedades psicométricas: confiabilidade (consistência interna e teste-reteste) e validade de construto. O reteste foi realizado quatro semanas após a primeira entrevista. RESULTADOS: a confiabilidade do instrumento foi avaliada por meio do Coeficiente α Cronbach, tendo como resultado geral 0,7. O teste-reteste avaliou a estabilidade do instrumento por meio do coeficiente de correlação intraclasse e apresentou resultado de 0,91 e 0,95, quando comparados aos questionários ICIQ-OAB e ICIQ-SF, respectivamente. Comparando os instrumentos por meio do coeficiente de correlação de Pearson foi encontrado 0,7 (p=0,0001), o que confirma a validade de critério do estudo. A validade concorrente foi avaliada pela correlação entre algumas variáveis sociodemográficas e clínicas e o escore final do ICIQ-OAB. CONCLUSÃO: a versão em português do ICIQ-OAB traduzida e adaptada culturalmente para o português do Brasil apresentou confiabilidade e validade de constructo satisfatórias e foi considerada válida para avaliação dos sintomas miccionais irritativos de pacientes brasileiros de ambos os sexos.

Irritable bowel syndrome in women with chronic pelvic pain in a Northeast Brazilian city

PURPOSES: To determine the prevalence of irritable bowel syndrome (IBS) in women with chronic pelvic pain (CPP) and its associated features; to determine whether IBS and CPP constitute the same syndrome. METHODS: Cross-sectional population survey with systematic sequential sampling according to census districts in which 1470 women were interviewed with respect to the sample calculation. The participants resided in their own homes, were at least 14 years of age, experienced menarche and presented CPP according to the American College of Obstetrics and Gynaecology. The dependent variable was IBS based on Rome III criteria in women with CPP, and the following independent variables were possibly associated with IBS: age, schooling, duration of pain, sedentary lifestyle, migraine, depression, insomnia, back pain, dysmenorrhea, dyspareunia, depression, history of violence, and intestinal symptoms. The sample was subdivided into groups with and without IBS. After the descriptive analysis of the variables was performed, the respective frequencies were evaluated using GraphPad Prism 5 software. To evaluate the association between the dependent variable and the independent variables, the χ² test was used with a significance level of 5%. RESULTS: The prevalence of IBS in women with CPP was 19,5%. Pain duration (p=0.03), back pain (p=0.002), history of physical or sexual abuse (p=0.002), and intestinal complaints were more prevalent in the group with IBS and CPP. There was no difference between the groups regarding other criteria. CONCLUSION: The data confirmed the literature, identified several aspects that were shared between the pathologies and supported the hypothesis that both pathologies can constitute the same syndrome.

Efficacy of paraspinal anesthetic block in patients with chronic pelvic pain refractory to drug therapy: a randomized clinical trial

PURPOSE: To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy.METHODS: Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI).RESULTS: Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03.CONCLUSIONS:Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.

The Influence of Education and Depression on Autonomy of Women with Chronic Pelvic Pain: A Cross-sectional Study

Objective Patient autonomy has great importance for a valid informed consent in clinical practice. Our objectives were to quantify thedomains of patient autonomy and to evaluate the variables that can affect patient autonomy in women with chronic pelvic pain. Methods This study is a cross sectional survey performed in a tertiary care University Hospital. Fifty-two consecutive women scheduled for laparoscopic management of chronic pelvic were included. Three major components of autonomy (competence, information or freedom) were evaluated using a Likert scale with 24 validated affirmatives. Results Competence scores (0.85 vs 0.92; p = 0.006) and information scores (0.90 vs 0.93; p = 0.02) were low for women with less than eight years of school attendance. Information scores were low in the presence of anxiety (0.91 vs 0.93; p = 0.05) or depression (0.90 vs 0.93; p = 0.01). Conclusions Our data show that systematic evaluation of patient autonomy can provide clinical relevant information in gynecology. Low educational level, anxiety and depression might reduce the patient autonomy in women with chronic pelvic pain.

Translation and Cross-Cultural Adaptation of the Lymphoedema Functioning, Disability and Health Questionnaire for Lower Limb Lymphoedema into Portuguese Language

Objective The objective of the study is to describe the process of translation and cross-cultural adaptation of the Lymphoedema Functioning, Disability, and Health Questionnaire for Lower Limb Lymphoedema (Lymph-ICF-LL) into (Brazilian) Portuguese. Methods The process was comprised of five steps - translation, back translation, revision by an expert panel, pretest, and final translation. The first translation was performed by two professionals of the healthcare area, and the back translation was performed by two translators. An expert panel assessed the questions for semantics and idiomatic, cultural, and conceptual equivalence. The pretest was conducted on 10 patients with lymphedema. Results Small differences were identified between the translated and back-translated versions, which were revised by the expert panel. The patients included in the pretest found 10 questions difficult to understand; these questions were reassessed by the same expert panel. Conclusion The results of the translation and cross-cultural adaptation of the Lymph- ICF-LL resulted in a Brazilian Portuguese version, which still requires validation with various samples of the local population.