RESUMO
CONTEXT: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier. OBJECTIVE: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin. Furthermore, we wished to examine the expression of the adiponectin receptors 1 and 2 (AdipR1, AdipR2) in the human hypothalamus. METHODS: For this purpose, serum and CSF samples were collected from 20 men and 19 women matched for age [men, 69.8 +/- 8.6 yr (mean +/- SD); women, 69.4 +/- 4.3 yr] and BMI (men, 29.4 +/- 3.4 kg/m(2); women, 27.3 +/- 4.8 kg/m(2)) undergoing elective surgery under spinal anesthesia. RESULTS: Adiponectin was identified in CSF with levels 1000-fold less than serum, whereas resistin and leptin levels were 100-fold less. Unlike their serum levels, adiponectin CSF levels showed no gender difference or correlation with insulin resistance, which is similar to resistin CSF levels. The adiponectin and leptin CSF/serum ratios in our study exhibit the same pattern of gender-specific BMI association with inverse correlation in women (r = -0.61; P = 0.02) and no correlation in men (r = 0.026; P = not significant). Furthermore, immunostaining established AdipR1 and -2 in the hypothalamus and increased AdipR2 expression in the paraventricular nucleus, which is involved in energy regulation. CONCLUSION: In summary, our findings show both the presence of adiponectin and resistin in human CSF, with no effect of insulin resistance on CSF levels. The CSF entry of adiponectin and leptin in women appears to be impaired in obesity.
Assuntos
Adiponectina/líquido cefalorraquidiano , Hipotálamo/metabolismo , Receptores de Superfície Celular/metabolismo , Resistina/líquido cefalorraquidiano , Adiponectina/sangue , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Leptina/sangue , Leptina/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Receptores de Adiponectina , Resistina/sangueRESUMO
Chronic pain has been arbitrarily defined as any pain lasting for more than twelve weeks. Chronic pain has also been defined as pain that continues beyond the time in which recovery might usually be expected. This suggests that the cause of pain may change, as it evolves into chronic pain.
Assuntos
Dor/tratamento farmacológico , Dor/fisiopatologia , Animais , Sistema Nervoso Central/fisiopatologia , Doença Crônica , Humanos , Sistema Nervoso Periférico/fisiopatologiaRESUMO
BACKGROUND: Tapentadol prolonged release (PR; 100-250 mg twice daily) has been efficacious and well tolerated for managing moderate-to-severe, chronic osteoarthritis hip or knee pain in phase 3 studies with washout of previous analgesic treatment. OBJECTIVE: The objective of this study was to evaluate the effectiveness and tolerability of tapentadol PR (50-250 mg twice daily) after direct rotation from World Health Organization (WHO) step III opioids in patients with severe osteoarthritis knee pain who previously responded to WHO step III therapy but showed poor tolerability. METHODS: This open-label, phase 3b study (NCT00982280) was conducted from October 2009 through June 2010 (prematurely terminated due to slow recruitment and study drug shortages) in clinical care settings in Europe and Australia. The study population included patients with severe, chronic osteoarthritis knee pain who had taken WHO step III opioids daily for ≥2 weeks before screening, responded to therapy (average pain intensity [11-point numerical rating scale-3 (NRS-3)] ≤5 at screening), and reported opioid-related adverse effects as their reason for changing analgesics. Patients switched directly from WHO step III therapy to tapentadol. Patients received oral tapentadol PR (50-250 mg twice daily) during 5-week titration and 7-week maintenance periods. Oral tapentadol immediate release (IR) was permitted (≤twice/day, ≥4 h apart) for acute pain episodes due to index pain or withdrawal symptoms following discontinuation of previous opioids (combined dose of tapentadol [PR and IR] ≤500 mg/day). This study was planned to evaluate conversion to tapentadol PR, based on responder rate 1 (percentage of patients with same/less pain [NRS-3] versus Week -1) at Week 6 (primary endpoint), adverse events (AEs), and discontinuation rates. Equianalgesic ratios were calculated for tapentadol prior to WHO step III opioids (PR and PR plus IR formulations). RESULTS: Of 82 patients enrolled, 63 received study medication. In the per-protocol population, responder rate 1 at Week 6 (last observation carried forward) was 94.3 % (50/53; P < 0.0001 vs. the null hypothesis rate [<60 %]). Mean (standard deviation) pain intensity scores were 4.7 (0.66) at baseline, 2.5 (1.46) at Week 6, and 1.8 (1.41) at Week 12 in the main analysis population (change from baseline at Weeks 6 and 12, P < 0.0001). Tapentadol to transdermal buprenorphine equianalgesic ratios (PR [n = 48], 262.9:1; PR plus IR [n = 48], 281.1:1) and tapentadol to oral oxycodone equianalgesic ratios (PR [n = 4], 4.3:1; PR plus IR [n = 6], 4.6:1) were calculated for the main analysis population. In the safety population, prevalence of AEs reported as associated with prior opioids at Week -1 (reasons for rotation) and related to tapentadol treatment at Week 12 decreased over time; the most common were nausea (46.0 vs. 24.1 %) and constipation (31.7 vs. 7.4 %). Overall, 14.3 % of patients discontinued the study early; reasons included AEs (9.5 %), lack of efficacy (3.2 %), and withdrawal of consent (1.6 %). CONCLUSIONS: Significant improvements in effectiveness were observed for tapentadol PR (50-250 mg twice daily) versus WHO step III opioids in patients with severe, chronic osteoarthritis knee pain who previously responded to WHO step III therapy. Equianalgesic ratios were calculated for tapentadol to transdermal buprenorphine and oral oxycodone and were in line with observations from previous phase 3 studies.
Assuntos
Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Fenóis/uso terapêutico , Receptores Opioides mu/agonistas , Idoso , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/tratamento farmacológico , Fenóis/efeitos adversos , TapentadolRESUMO
Research has increased our understanding of the psychological and physical functioning associated with persistent pain and has facilitated the development of cognitive behavioral pain management programs to help improve people's physical function and decrease their distress in the presence of persistent pain. The majority of this research has focused on nociceptive pain or pain of mixed etiology. There has been less focus on these aspects of neuropathic pain. It is possible that differences exist in the function and difficulties associated with nociceptive and neuropathic pain. These differences may be associated with our clinical observation that some people with neuropathic pain have difficulty applying some aspects of the theory and practice of cognitive behavioral pain management. The purpose of this study was to compare a single neuropathic pain condition (post-herpetic neuralgia) with a persistent pain of nociceptive origin (low back pain) and determine whether differences exist in: (1) physical and psychological function; (2) factors that increase difficulties; (3) responses to pain; (4) beliefs about pain and (5) problems experienced. The results suggest that the differences between the two groups were not on the major variables of pain, mood, cognition and physical function. The main differences were in factors that increase pain, people's responses to pain, their beliefs about diagnosis and the cause of pain and the problems they reported as a result of experiencing pain. The implications of our findings for the development of cognitive behavioral pain management programs for people with neuropathic pain are discussed.
Assuntos
Terapia Cognitivo-Comportamental , Dor Lombar , Atividade Motora , Neuralgia Pós-Herpética , Adulto , Sintomas Afetivos/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Atitude Frente a Saúde , Aprendizagem da Esquiva , Doença Crônica , Depressão/diagnóstico , Feminino , Humanos , Dor Lombar/fisiopatologia , Dor Lombar/psicologia , Dor Lombar/terapia , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/fisiopatologia , Neuralgia Pós-Herpética/psicologia , Neuralgia Pós-Herpética/terapia , Nociceptores/fisiologia , Inquéritos e QuestionáriosRESUMO
Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.
Assuntos
Analgésicos/administração & dosagem , Hiperestesia/tratamento farmacológico , Neuralgia/tratamento farmacológico , Doenças do Sistema Nervoso Periférico , Extratos Vegetais/administração & dosagem , Administração Intranasal , Adolescente , Adulto , Idoso , Canabidiol , Método Duplo-Cego , Dronabinol , Combinação de Medicamentos , Feminino , Humanos , Hiperestesia/etiologia , Masculino , Pessoa de Meia-Idade , Neuralgia/complicações , Medição da Dor/métodos , Desempenho Psicomotor/efeitos dos fármacos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS AND OBJECTIVES: This review aims to explore the research available relating to three commonly used pain rating scales, the Visual Analogue Scale, the Verbal Rating Scale and the Numerical Rating Scale. The review provides information needed to understand the main properties of the scales. BACKGROUND: Data generated from pain-rating scales can be easily misunderstood. This review can help clinicians to understand the main features of these tools and thus use them effectively. METHOD: A MedLine review via PubMed was carried out with no restriction of age of papers retrieved. Papers were examined for methodological soundness before being included. The search terms initially included pain rating scales, pain measurement, Visual Analogue Scale, VAS, Verbal Rating Scale, VRS, Numerical/numeric Rating Scale, NRS. The reference lists of retrieved articles were used to generate more papers and search terms. Only English Language papers were examined. CONCLUSIONS: All three pain-rating scales are valid, reliable and appropriate for use in clinical practice, although the Visual Analogue Scale has more practical difficulties than the Verbal Rating Scale or the Numerical Rating Scale. For general purposes the Numerical Rating Scale has good sensitivity and generates data that can be statistically analysed for audit purposes. Patients who seek a sensitive pain-rating scale would probably choose this one. For simplicity patients prefer the Verbal Rating Scale, but it lacks sensitivity and the data it produces can be misunderstood. RELEVANCE TO CLINICAL PRACTICE: In order to use pain-rating scales well clinicians need to appreciate the potential for error within the tools, and the potential they have to provide the required information. Interpretation of the data from a pain-rating scale is not as straightforward as it might first appear.