Pain and quality of life in patients undergoing radiotherapy for spinal metastatic disease treatment

Background: Radiotherapy is an important tool in the control of pain in patients with spinal metastatic disease. We aimed to evaluate pain and of quality of life of patients with spinal metastatic disease undergoing radiotherapy with supportive treatment. Methods. The study enrolled 30 patients. From January 2008 to January 2010, patients selection included those treated with a 20Gy tumour dose in five fractions. Patients completed the visual analogue scale for pain assessment and the SF-36 questionnaire for quality of life assessment. Results: The most frequent primary sites were breast, multiple myeloma, prostate and lymphoma. It was found that 14 spinal metastatic disease patients (46.66%) had restricted involvement of three or fewer vertebrae, while 16 patients (53.33%) had cases involving more than three vertebrae. The data from the visual analogue scale evaluation of pain showed that the average initial score was 5.7 points, the value 30days after the end of radiotherapy was 4.60 points and the average value 6months after treatment was 4.25 points. Notably, this final value was 25.43% lower than the value from the initial analysis. With regard to the quality of life evaluation, only the values for the functional capability and social aspects categories of the questionnaire showed significant improvement. Conclusion: Radiotherapy with supportive treatment appears to be an important tool for the treatment of pain in patients with spinal metastatic disease. © 2013 Valesin Filho et al; licensee BioMed Central Ltd.

IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma

Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Cognitive function in patients with chronic pain treated with opioids: characteristics and associated factors

Background The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated with opioids. Methods In this cross-sectional study, 49 patients were assessed by Continuous Reaction Time, Finger Tapping, Digit Span, Trail Making Test-B and Mini-mental State Examination tests. Linear regressions were applied. Results Patients scored poorly in the Trail Making Test-B (mean?=?107.6?s, SD?=?61.0, cut-off?=?91?s); and adequately on all other tests. Several associations among independent variables and cognitive tests were observed. In the multiple regression analyses, the variables associated with statistically significant poor cognitive performance were female sex, higher age, lower annual income, lower schooling, anxiety, depression, tiredness, lower opioid dose, and more than 5?h of sleep the night before assessment (P?<?0.05). Conclusions Patients with chronic pain may have cognitive dysfunction related to some reversible factors, which can be optimized by therapeutic interventions.

[Drug therapy of acute and chronic abdominal pain]

For drug therapy a differentiation of acute and chronic pain is essential. In emergency situations of acute abdominal pain a fast diagnosis is mandatory. Analgesia should be provided as soon as possible. The different groups of analgesics should be used according to their known effects, side effects and contraindications. Postoperative pain after abdominal surgery has to be considered as a special condition of acute abdominal pain. Main treatment options are non opioid analgesics and opioids. Opioids can be administered intravenously via patient controlled analgesia (PCA) devices. In major abdominal surgery neuroaxial analgesia, preferentially administered via an epidural catheter provides excellent pain relief with positive impact on gastrointestinal motility and patients' recovery. Because of difficulties to allocate chronic abdominal pain to a specific organ, causal treatment often turns out to be difficult. Peripheral and central sensitization, as well as an alteration of the endogenous pain modulation comes to the fore in these chronic pain conditions. Co-analgesics like anticonvulsants and antidepressants are utilized to reduce sensitization and improve the endogenous pain modulating system. Non drug approaches and alternative treatment options might be useful. In contrast, orally or transcutaneously administered opioids are the principal corner stone for the treatment of cancer pain.

Quality of analgesic treatment in patients with advanced prostate cancer: do we do a better job now? The Swiss Group for Clinical Cancer Research (SAKK) experience

GOALS OF WORK: The aim of this study was to evaluate pain intensity and the application of the WHO guidelines for cancer pain treatment in patients with prostate cancer treated at Swiss cancer centers. MATERIALS AND METHODS: We analyzed a series of five multicenter phase II clinical trials which examined the palliative effect of different chemotherapies in patients with advanced hormone-refractory prostate carcinoma. Of 170 patients, 1,018 visits were evaluable for our purpose, including ratings of pain intensity by patients and prescribed analgesics. MAIN RESULTS: No or mild pain was indicated by patients in 36 to 55% of the visits, more than mild pain in 30 to 46%. In 21% of the visits, the WHO pain treatment criteria (treatment according to one of the three steps; oral, rectal or transdermal application of the main dose; administration on a regular schedule) were fulfilled, and the Cleeland index was positive according to all recommendations. In 6% of the visits, neither the WHO criteria were fulfilled nor was the Cleeland index positive. This indicates insufficient pain treatment not following the WHO guidelines and that the prescribed analgesics were not sufficiently potent for the rated pain intensity. CONCLUSIONS: In this selective Swiss sample, the standard of analgesic treatment is high. However, there is still scope for improvement. This cannot solely be solved by improving the knowledge of the physicians. Programs to change the patients' attitude towards cancer pain, training to improve the physicians' communication skills, and institutional changes may be promising strategies.

A visceral pain pathway in the dorsal column of the spinal cord

A limited midline myelotomy at T10 can relieve pelvic cancer pain in patients. This observation is explainable in light of strong evidence in support of the existence of a visceral pain pathway that ascends in the dorsal column (DC) of the spinal cord. In rats and monkeys, responses of neurons in the ventral posterolateral thalamic nucleus to noxious colorectal distention are dramatically reduced after a lesion of the DC at T10, but not by interruption of the spinothalamic tract. Blockade of transmission of visceral nociceptive signals through the rat sacral cord by microdialysis administration of morphine or 6-cyano-7-nitroquinoxaline-2,3-dione shows that postsynaptic DC neurons in the sacral cord transmit visceral nociceptive signals to the gracile nucleus. Retrograde tracing studies in rats demonstrate a concentration of postsynaptic DC neurons in the central gray matter of the L6-S1 spinal segments, and anterograde tracing studies show that labeled axons ascend from this region to the gracile nucleus. A similar projection from the midthoracic spinal cord ends in the gracile and cuneate nuclei. Behavioral experiments demonstrate that DC lesions reduce the nocifensive responses produced by noxious stimulation of the pancreas and duodenum, as well as the electrophysiological responses of ventral posterolateral neurons to these stimuli. Repeated regional blood volume measurements were made in the thalamus and other brain structures in anesthetized monkeys in response to colorectal distention by functional MRI. Sham surgery did not reduce the regional blood volume changes, whereas the changes were eliminated by a DC lesion at T10.

The role of morphine-6-glucuronide (M6G) in pain control

Morphine-6beta-D-glucuronide (M6G) is an analgesically active metabolite of morphine, accounting for approximate to10% of the morphine dose when administered by systemic routes to humans. Although M6G is more hydrophilic than morphine, it crosses the blood-brain barrier, albeit relatively slowly. For this reason, it is generally thought that, after chronic dosing, M6G contributes significantly to the analgesic effects of systemically administered morphine. Owing to its polar nature, M6G is cleared from the systemic circulation primarily via renal elimination. As M6G accumulates in patients with renal impairment, there is an increased risk of M6G-induced respiratory depression in renal failure patients who are being dosed chronically with systemic morphine. Consistent with its analgesic and respiratory depressant properties, M6G binds to the p-opioid receptor in a naloxone-reversible manner. Although the affinity of M6G for the mu-opioid receptor is similar to or slightly less than that of morphine, preclinical studies in rodents show that M6G is one to two orders of magnitude more potent than morphine when administered by central routes. This major discrepancy between the markedly higher intrinsic antinociceptive potency of M6G relative to morphine, despite their similar p-opioid receptor binding affinities, is difficult to reconcile. It has been proposed that M6G mediates its pain-relieving effects through a novel 'M6G opioid receptor', while others have argued that M6G may have higher efficacy than morphine for transduction of intracellular events. When administered by parenteral routes to rodents, M6G's antinociceptive potency is no more than twofold higher than morphine. In humans, the analgesic efficacy and respiratory depressant potency of M6G relative to morphine have been assessed in a number of short-term studies involving the intrathecal or intravenous routes of administration. For example, in hip replacement patients, intrathecal M6G provided excellent postoperative analgesia but the occurrence of late respiratory depression in 10% of these patients raised serious concern about safety. In postoperative patients, intravenous M6G administered by means of patient-controlled analgesia (PCA), or bolus plus PCA, produced no analgesia in one study and limited analgesia in another. Similarly, there was a lack of significant analgesia in healthy volunteers who received intravenous M6G for the alleviation of experimental pain (carbon dioxide applied to the nasal mucosa). In contrast, satisfactory analgesia was produced by bolus doses of intravenous M6G administered to patients with cancer pain, and to healthy volunteers with experimentally-induced ischaemic, electrical or thermal (ice water) pain. Studies to date in healthy volunteers suggest that intravenous M6G may be a less potent respiratory depressant and have a lower propensity for producing nausea and vomiting than morphine. However, it is unclear whether equi-analgesic doses of M6G and morphine were compared. Clearly, more extensive short-term trials, together with studies involving chronic M6G administration, are necessary before the potential clinical utility of M6G as an analgesic drug in its own right can be determined.

Identification of symptom clusters in patients with chronic venous leg ulcers

Context Patients with venous leg ulcers experience multiple symptoms, including pain, depression, and discomfort from lower leg inflammation and wound exudate. Some of these symptoms impair wound healing and decrease quality of life (QOL). The presence of co-occurring symptoms may have a negative effect on these outcomes. The identification of symptom clusters could potentially lead to improvements in symptom management and QOL. Objectives To identify the prevalence and severity of common symptoms and the occurrence of symptom clusters in patients with venous leg ulcers. Methods For this secondary analysis, data on sociodemographic characteristics, medical history, venous history, ulcer and lower limb clinical characteristics, symptoms, treatments, healing, and QOL were analyzed from a sample of 318 patients with venous leg ulcers who were recruited from hospital outpatient and community nursing clinics for leg ulcers. Exploratory factor analysis was used to identify symptom clusters. Results Almost two-thirds (64%) of the patients experienced four or more concurrent symptoms. The most frequent symptoms were sleep disturbance (80%), pain (74%), and lower limb swelling (67%). Sixty percent of patients reported three or more symptoms at a moderate-to-severe level of intensity (e.g., 78% reported disturbed sleep frequently or always; the mean pain severity score was 49 of 100, SD 26.5). Exploratory factor analysis identified two symptom clusters: pain, depression, sleep disturbance, and fatigue; and swelling, inflammation, exudate, and fatigue. Conclusion Two symptom clusters were identified in this sample of patients with venous leg ulcers. Further research is needed to verify these symptom clusters and to evaluate their effect on patient outcomes.

Flupirtine enhances the anti-hyperalgesic effects of morphine in a rat model of prostate bone metastasis

Objective Current treatments for cancer pain are often inadequate, particularly when metastasis to bone is involved. The addition to the treatment regimen of another drug that has a complementary analgesic effect may increase the overall analgesia without the necessity to increase doses, thus avoiding dose-related side effects. This project investigated the synergistic effect of the addition of the potassium channel (KCNQ2–3) modulator flupirtine to morphine treatment in a rat model of prostate cancer-induced bone pain. Design Syngeneic prostate cancer cells were injected into the right tibia of male Wistar rats under anesthesia. This led to expanding tumor within the bone in 2 weeks, together with the concurrent development of hyperalgesia to noxious heat. Paw withdrawal thresholds from noxious heat were measured before and after the maximum non-sedating doses of morphine and flupirtine given alone and in combinations. Dose-response curves for morphine (0.13–5.0 mg/kg ip) and flupirtine (1.25–10.0 mg/kg ip) given alone and in fixed-dose combinations were plotted and subjected to an isobolographic analysis. Results Both morphine (ED50 = 0.74 mg/kg) and flupirtine (ED50 = 3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation. Isobolographic analysis revealed that there was a synergistic interaction between flupirtine and morphine. Addition of flupirtine to morphine treatment improved morphine anti-hyperalgesia, and resulted in the reversal of cancer-induced heat hyperalgesia. Conclusions These results suggest that flupirtine in combination with morphine may be useful clinically to provide better analgesia at lower morphine doses in the management of pain caused by tumors growing in bone.

The lipophilic opioids: Fentanyl, alfentanil, sufentanil and remifentanil

discusses fentanyl, alfentanil, sufentanil, and remifentanil which are synthetic opioid analgesics with high affinity for the mu opioid receptor. They have been widely adopted in anaesthetic practice for various surgical procedures (e.g. in cardiac surgery) and for long-term analgesia and sedation. Important pharmacokinetic differences between these analgesics have been described, and this chapter addresses how the pharmacokinetic profile of each analgesic is affected by many factors, including patient age, plasma protein content, acid–base balance status, cardiopulmonary bypass, changes in hepatic blood flow, and the co-administration of other drugs which compete for plasma protein carriers and metabolic pathways, although their profile is not significantly affected by renal insufficiency or compensated hepatic dysfunction, which has major clinical implications.

Laços e nós: A comunicação na relação médico- paciente com câncer e dor crônica

É alta a prevalência de dor crônica em pacientes com câncer, que é comprovadamente associada ao sofrimento psicológico acentuado e muitas vezes não é adequadamente diagnosticada e tratada. Estudo que realizamos com 120 pacientes adultos em atendimento ambulatorial na Clínica de Dor do Instituto Nacional de Câncer, no Rio de Janeiro que demonstrou que os pacientes mesmo conhecendo o seu diagnóstico de câncer, não se sentiam informados sobre a doença e a dor oncológica a contento, o que trazia insatisfação com o tratamento recebido e maior exigência com os resultados do mesmo. Nosso estudo revelou, ainda, que o comportamento do profissional durante o atendimento pode ser percebido pelos pacientes como fator tanto de melhora como de piora da dor, sendo o comportamento atencioso do profissional muitas vezes mais valorizado pelos pacientes que a supressão da dor. Estes resultados suscitaram questões relativas à qualidade da interação entre médicos e pacientes, desenvolvidas nesta dissertação. Embora não sejam suficientemente investidas nem na relação médico-paciente, nem na educação e no treinamento profissional, as habilidades de comunicação do médico afetam diretamente o nível de informação e de satisfação do paciente, suas crenças e os resultados do tratamento. Ao longo do tempo a relação médico paciente vem mudando, deixando de ser tão centrada na doença e no médico, para centrar-se mais no doente como um ser integral, o que implica no reconhecimento, pelo médico, de saberes diferentes dos seus e de que o seu saber não constitui uma verdade absoluta a ser acatada pelos demais. Apesar de bem-vindas, estas mudanças trazem uma certa confusão nos papéis a serem desempenhados por médicos e pacientes e dificuldades aos médicos de lidarem com as diferenças, com as queixas subjetivas dos pacientes, com as emoções destes e as suas próprias. Se hoje é esperado que os pacientes sejam participativos, corresponsáveis por seus tratamentos e recuperação e que se deem conta do poder que eles têm, individual e coletivamente, espera-se que os médicos sejam estudiosos, bem informados, experientes, sinceros, empáticos, sensíveis, atenciosos, compassivos, perspicazes, bem treinados, hábeis em compartilhar informações e decisões com os pacientes, compreendendo o que estes querem e o que não querem e ajudando-os a expressar suas crenças, preferências e receios, disponibilizando tempo suficiente para isso. Tantas expectativas terminam por trazer conflitos que só poderão ser resolvidos com a melhoria da comunicação entre médicos e pacientes, num esforço de ambas as partes.

克洛曲对癌痛的双盲双模拟自身交叉研究

为了观察克洛曲在慢性癌痛病人中的疗效,采用多中心、双盲双模拟、自身交叉对照研究的方法, 比较了克洛曲片、曲马多胶囊和安慰剂对108 例中、重度癌痛的镇痛效果。结果表明克洛曲片的总有效率为 88. 0 % ,明显高于曲马多胶囊的72. 2 %( P < 0. 01) 和安慰剂的35. 2 %( P < 0. 001) ; 克洛曲片的缓解时间明 显延长( P < 0. 01) ; 克洛曲片的药物不良反应的发生率与曲马多胶囊相似, 但便秘的发生率明显低于曲马 多胶囊( P < 0. 05) 。克洛曲片对中、重度癌痛的镇痛效果确切,安全性较大。文章还对镇痛药临床研究的策 略方法及安慰剂效应进行了详细的讨论。

A shared care model pilot for palliative home care in a rural area:Impact on symptoms, distress, and place of death

Context: Shared care models integrating family physician services with interdisciplinary palliative care specialist teams are critical to improve access to quality palliative home care and address multiple domains of end-of-life issues and needs. Objectives: To examine the impact of a shared care pilot program on the primary outcomes of symptom severity and emotional distress (patient and family separately) over time and, secondarily, the concordance between patient preferences and place of death. Methods: An inception cohort of patients (n = 95) with advanced, progressive disease, expected to die within six months, were recruited from three rural family physician group practices (21 physicians) and followed prospectively until death or pilot end. Serial measurement of symptoms, emotional distress (patient and family), and preferences for place of death was performed, with analysis of changes in distress outcomes assessed using t-tests and general linear models. Results: Symptoms trended toward improvement, with a significant reduction in anxiety from baseline to 14 days noted. Symptom and emotional distress were maintained below high severity (7-10), and a high rate of home death compared with population norms was observed. Conclusion: Future controlled studies are needed to examine outcomes for shared care models with comparison groups. Shared care models build on family physician capacity and as such are promising in the development of palliative home care programs to improve access to quality palliative home care and foster health system integration. © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Avaliação dos níveis de ansiedade e depressão e sua correlação com a intensidade de dor em doentes oncológicos com doença avançada e progressiva

Tese de mestrado, Cuidados Paliativos, Faculdade de Medicina, Universidade de Lisboa, 2015