A blinded, randomized and controlled multicenter field study investigating the safety and efficacy of long-term use of enflicoxib in the treatment of naturally occurring osteoarthritis in client-owned dogs.

Background: Enflicoxib is a COX-2 selective NSAID shown to be efficacious and safe in the treatment of pain and inflammation associated with canine osteoarthritis (OA) in clinical studies of 6 weeks duration. Objective: This prospective, multisite, blinded, randomized, placebo-controlled, parallel-group field study aimed to confirm the safety and efficacy of enflicoxib in long-term canine OA treatments. Animals: A total of 109 client owned dogs with clinical and radiographic signs of OA for at least 3 weeks were enrolled with 78 dogs completing all study visits. Methods: Dogs were randomized at a 3:1 ratio to receive enflicoxib (n = 83) or placebo (n = 26) once weekly during 6 months. Dogs underwent veterinary assessments from Day 0 to Day 189 using a clinical sum score (CSS). Efficacy was also assessed by the owners using the Canine Brief Pain Inventory (CBPI). Safety was assessed clinically and by repeated blood and urine sample analysis. The efficacy outcome measure was the treatment response according to the CSS and secondarily the treatment response according to the CBPI. The primary safety outcome was the incidence of adverse events (AEs) and secondarily the evolution of the clinical pathology parameters. Results: Percentages of CSS responders for enflicoxib were 71.6; 74.6 and 71.6% on Days 44, 135 and 189 respectively, always showing statistically significant differences (p < 0.05) vs. placebo (41.7, 33.3, and 20.8% respectively). Treatment response according to owner assessments followed the same pattern, achieving significant differences compared to placebo after 2 weeks of treatment. The incidence and type of AEs were as described in previous enflicoxib studies of shorter duration and as for other NSAIDs, with no tendency to increase over time. No relevant changes in hematology, biochemistry or urine parameters were observed. Conclusions and clinical relevance: Enflicoxib safety and efficacy profile is maintained after a long-term treatment, which together with its weekly administration, makes it a good alternative for the chronic treatment of dogs with naturally occurring OA.

[Tumor-associated pain]. / Tumorassoziierter Schmerz.

Tumor-associated pain has a high prevalence and is still a challenging aspect of pain medicine. Treatment-related etiologies often coexist with pain caused by the oncological disease itself. For cancer pain as well, a pathophysiologically oriented analysis of nociceptive, nociplastic and neuropathic pain is advisable for planning a tailored treatment. The analgesic three-step ladder of the World Health Organization (WHO) should be customized in this context, incorporating antineuropathic or antihypersensitizing pharmacological approaches as well as minimally invasive techniques. Psycho-oncological and exercise therapy interventions should be considered. In cases of long-term courses of treatment or following curative oncological treatment, chronically persistent or chronic tumor-associated pain can occur, necessitating multimodal therapeutic approaches analogue to noncancer pain conditions. Close integration with palliative medicine enhances the therapeutic effectiveness during the transition from nonpalliative to palliative treatment phases.

Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives.

BACKGROUND: Two studies demonstrated the efficacy and safety of naldemedine in adult patients with chronic non-cancer pain and opioid-induced constipation (OIC). However, no studies have compared the efficacy of peripherally acting µ-opioid receptor antagonists in patients with adequate and inadequate responses to prior OIC therapy with laxatives. This post hoc analysis of integrated data from the two previous studies compared the efficacy of naldemedine in patients who were unsuccessfully treated with laxatives [poor laxative responders (PLRs)] with those who either did not receive laxatives >30 days prior to screening or those who only received rescue laxative at or after screening (non-PLRs). METHODS: Patients with OIC were randomized to once-daily treatment with naldemedine 0.2 mg or placebo. The primary efficacy endpoint was the proportion of responders [⩾3 spontaneous bowel movements (SBMs)/week and an increase from baseline of ⩾1 SBM/week for ⩾9 weeks of the 12-week treatment period and ⩾3 weeks of the final 4 weeks of the 12-week treatment period]. Additional endpoints included change in SBM frequency, change in frequency of SBMs without straining, proportion of complete SBM (CSBM) responders, change in CSBM frequency, and time to first SBM. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: The analysis included 538 (317 PLRs, 221 non-PLRs) and 537 (311 PLRs, 226 non-PLRs) patients in the naldemedine and placebo arms, respectively. There were significantly more responders in the naldemedine PLR (46.4%; p < 0.0001) and non-PLR (54.3%; p = 0.0009) subgroups versus the placebo groups (30.2% and 38.9%, respectively). In both the PLR and non-PLR subgroups, naldemedine treatment was superior to placebo on all additional endpoints. Overall incidence of TEAEs in the PLR subgroups treated with naldemedine or placebo was similar. CONCLUSION: This integrated analysis further supports the efficacy and tolerability of naldemedine in the treatment of OIC and demonstrates a consistent effect in both PLR and non-PLR subgroups.[ClinicalTrials.gov identifier: NCT01965158 and NCT01993940].

Access to Controlled Medicines in Low-Income Countries: Listening to Stakeholders in the Field.

Little is known on current practices and challenges associated with the legal trade of medicines controlled under international conventions in low-income countries. This qualitative survey involved semi-structured interviews of stakeholders engaged in the trade of controlled medicines at a global level or at a country level in 3 African countries (Uganda, Kenya, Democratic Republic of the Congo). Nine interviews were conducted, including 3 international wholesalers, 2 relief organizations, 2 procurement officers, and 2 regulatory officers. Additionally, 4 other participants provided written information. All participants consistently reported that the current process of procuring controlled medicines in compliance with international conventions was long and complex given the number of administrative steps required for obtaining export and import authorizations, which are mandatory for both narcotic and psychotropic medicines. It may be difficult or impossible to obtain import authorizations from some health authorities in low-income countries because of long delays, mistakes in forms, absence or shortage of staff, or when annual national estimates are exceeded. The complexities of the trade of controlled medicines directly contribute to the lack of access to essential controlled medicines, both narcotics and psychotropics, in low-income countries.

Subgroup analysis of the early paracetamol trial to preterm infants found haemodynamic changes and improved oxygenation.

BACKGROUND: We previously reported in a randomised trial that early intravenous paracetamol accelerated contraction of ductus arteriosus in very preterm infants (<32 gestation weeks). AIMS: To monitor sequentially paracetamol effects on the blood pressure and brain tissue oxygenation in the infants participating the trial. METHODS: In a double-blind trial, intravenous paracetamol or placebo was infused to 48 very premature infants starting within 24 h of birth for four days. Besides the ductus arteriosus, we systematically measured blood pressure, peripheral (spO2) and regional cerebral oxygen saturation (rcSO2), and cerebral fractional tissue oxygen extraction (cFTOE) during the study period. RESULTS: Compared to the placebo, the paracetamol loading dose transiently decreased the arterial blood pressure. During treatment, the paracetamol-treated infants had higher spO2 (p = .042) and rcSO2 (p = .036) values than the placebo group infants. Additionally, the cFTOE values were lower in the paracetamol group during the study without statistical significance. All infants with closed ductus had higher tissue oxygenation and a lower cFTOE than infants with open ductus. CONCLUSIONS: Paracetamol caused modest haemodynamic effects and increased cerebral oxygenation. They were mostly due to early contraction of ductus. Additional direct drug-effects in brain are not ruled-out.

Inpatient pain management in sickle cell disease.

PURPOSE: A novel strategy for management of acute pain associated with sickle cell disease (SCD), referred to as the oral tier approach, is described. SUMMARY: SCD is an inherited blood disorder characterized by episodic acute pain known as vaso-occlusive crisis (VOC), which is the most common reason for emergency department visits and hospital admissions in patients with SCD; these patients are often treated with parenteral opioids on admission and then transitioned to oral opioids prior to discharge. In this report, experience with use of the oral tier approach in 3 patients with SCD hospitalized for management of VOC is reported. As per usual practice, acute pain was initially managed with parenteral opioids via patient-controlled analgesia (PCA). Once pain control was established, an oral tier was added. The oral tier consisted of 3 orders. The first order was for an oral opioid, to be administered every 3 hours on a scheduled basis; however, the patient could refuse 1 or more of these scheduled doses. Two additional orders specified that the patients could receive additional oral opioids in incremental doses for moderate (grade 4-7) or severe (grade 8-10) pain if appropriate. To facilitate transition to an oral regimen with which the patients might be discharged, they were encouraged to use oral opioids in preference to parenteral opioids. Opioid usage and average daily pain scores for the 3 patients are reported. CONCLUSION: Healthcare providers can use the oral tier approach to facilitate rapid inpatient conversion from i.v. PCA to oral opioids while providing adequate pain control in patients with SCD who develop VOC.

Tramadol prescribed use in general and chronic noncancer pain: a nationwide register-based cohort study of all patients above 16 years.

Background and aims In the Western world, it has become clear that we are facing a crisis of overuse, abuse and improperly prescribed use of opioids. As part of the ongoing discussion on opioid use, the use and prescription of tramadol have been addressed in recent years. A significant portion of this discussion should adequately address the risk factors for the use of weak opioid products such as tramadol. The risk factors which characterise the long-term tramadol use are still incompletely understood. Thus, we aimed to describe the characteristics of Danish patients using tramadol in more detail, under different scenarios and determinants of subsequent usage patterns. Methods We conducted a nationwide cohort study to identify individuals purchasing tramadol from 01/01/2004 to 31/12/2015 who are age 16 + years old by using data from The Danish National Databases; these databases consist of unique information for all citizens in Denmark. Logistic regression analyses were used to assess the potential risk factors for repeated tramadol use. Results The final cancer-free cohort consisted of N = 941,839 tramadol users: 54.4% women, with a mean age of 53.2 years. The number of chronic noncancer pain (CNCP) was 430,641 individuals, and 56% of the total third who repeated the use of tramadol with two + purchased prescriptions were CNCP patients. The increased risk of repeated use for CNCP was, among others, associated with: male sex (HR 1.21), age 69-110 (HR 1.72), back/spine pain men (HR 1.47), women (HR 1.46), spondylopathies (HR 1.24), male osteoporosis (HR 1.22), multimorbid ulcer/skin (HR 1.28), region of municipality Northern Jutland (HR 1.74), Central Jutland (HR 1.75), number of co-medication 4-9 (HR 1.33), dementia (HR 1.27). Factors associated with decreased risk: co-medication ischemic heart disease (HR 0.85), diagnosis headache (HR 0.70), household income highest tertile (HR 0.81), unknown (HR 0.70), single women (HR 0.96). Conclusions This study proved a widespread prescribed use of tramadol in Denmark, and, as know from the literature, weak opioid use may lead to long-term use of high potent opioids, this usage is inappropriate, in general, but especially for the treatment of CNCP. Implications When striving to reduce the overuse of opioids, focus on the extensive use of tramadol may be essential. The current study indicates an excessive and not appropriately prescribed use of tramadol among Danish CNCP patients. In addition to being inappropriate, such use may also have an impact on the growing problem of an illicit Internet market for this drug. Thus, the situation must be taken seriously. The current study confirms the recent clinical guideline and the National Recommendations in Denmark, which emphasises the risks of problematic use of tramadol. The research may also be relevant in other comparable countries. Caution must especially be taken with CNCP patients with comorbidities like diabetes, lung disease, dementia, and osteoporosis.

[Opioids for Cancer Pain and its Use under Particular Conditions: A Narrative Review]. / Opióides na Dor Oncológica e o seu Uso em Circunstâncias Particulares: Uma Revisão Narrativa.

INTRODUCTION: All health professionals should be aware of the importance of evaluating pain - fifth vital sign- in cancer patients. Peripheral and central acting analgesics are widely used to treat moderate to severe pain, particularly cancer pain. Many guidelines have addressed this issue. However, real life patients' have other problems and comorbidities that may raise doubts when prescribing. MATERIAL AND METHODS: Authors made a literature search, trying to clarify same specific situations: loss of oral route, renal impairment (hemodialysis), hepatic impairment, frequent opiod interactions and the availability of short-acting formulations. RESULTS: The following medicines were included in this analysis: the natural opiates (morphine and codeine), their synthetic and semisynthetic derivatives (hydromorphone, oxycodone, and fentanyl), the partial agonist buprenorphine and finally tramadol and tapentadol. Transdermal systems are only available for buprenorphine and fentanyl. In hepatic impairment, fentanyl is safe, but with the exception of codeine and tramadol; other opioids should be used with caution. In renal failure: fentanyl, hydromorphone, and tapentadol are safe. Morphine should be avoided; other opioids should be used with caution. In hemodialysis, buprenorphine, fentanyl, hydromorphone and tramadol (at doses up to 200 mg/day) may be used. DISCUSSION: Failure to recognize the impact of various situations described throughout this work, including the bioavailability due to loss of oral route, due to pharmacokinetics and pharmacodynamics of the various drugs, either in the context of the impaired metabolism or excretion, or in due to pharmacological interactions, conditions a serious risk of subtreatment of pain and consequent impact in terms of quality of life. CONCLUSION: Opioid prescription is safe and effective, even in moderate to severe comorbidities such as renal and hepatic impairment and in patients with no oral route available. In this case, as when considering pharmacological interactions, an individualized therapeutic plan is the best solution and the patient should be assessed regularly. Unadjusted doses may relate to bad pain control and a higher prevalence of adverse events.

Introdução: A dor é equiparada a quinto sinal vital e deve ser avaliada de forma sistemática em todas as consultas de um paciente com cancro. Os fármacos utilizados na prática oncológica para tratar os doentes com dor crónica moderada a severa incluem analgésicos de ação periférica e central que têm sido abordados em múltiplas diretrizes nacionais e internacionais. No entanto, na prática clínica há que equacionar outros problemas e eventuais comorbilidades, que podem levantar dúvidas no momento da prescrição.Material e Métodos: Fez-se uma revisão da literatura, tentando refletir sobre algumas situações específicas na utilização de opióides, nomeadamente perda da via oral, insuficiência renal (hemodiálise), insuficiência hepática, interações medicamentosas e formulações de ação imediata.Resultados: Os opiáceos naturais (morfina e codeína) e os seus derivados sintéticos e semissintéticos (hidromorfona, oxicodona, fentanilo), o agonista parcial buprenorfina e finalmente o tramadol e tapentadol foram selecionados para esta análise. Os sistemas transdérmicos estão apenas disponíveis para a buprenorfina e o fentanilo. Na insuficiência hepática, o fentanilo foi considerado seguro, mascom exceção da codeína e do tramadol, podem todos ser usados com precaução. Na insuficiência renal, o fentanilo, a hidromorfona e o tapentadol foram considerados seguros. Deve evitar-se a morfina, e os restantes poderão ser usados com precaução. Em pacientes em hemodiálise pode usar-se buprenorfina, fentanilo, hidromorfona e tramadol (em doses até 200 mg/dia).Discussão: O não reconhecimento do impacto das várias situações descritas ao longo deste trabalho, nomeadamente a alteração da biodisponibilidade por perda de via oral, por alteração da farmacocinética e farmacodinâmica dos vários fármacos, quer no contexto da insuficiência de órgão responsável pelo metabolismo ou excreção, quer no contexto das interações farmacológicas, condiciona umnorme risco de subtratamento da dor e consequente impacto em termos de qualidade de vida.Conclusão: A prescrição de opióides é segura e efetiva, mesmo em situações de comorbilidades moderadas a graves como insuficiência renal e hepática e em doentes sem via oral disponível. Neste caso, como quando considerámos as interações farmacológicas, o plano terapêutico deve ser individualizado e o paciente deve ser avaliado regularmente. A seleção inadequada e/ou dose mal ajustada de um fármaco, o não reconhecimento do impacto dos efeitos adversos, frequentemente justificam o mau controlo da dor e a toxicidade excessiva.

Pharmacoeconomic Aspects of Low Back Pain Treatment: Cost of Illness Study in the Republic of Serbia.

INTRODUCTION: Chronic diseases with disabilities have a huge pharmacoeconomic impact on the health budget, especially in countries with recent history of social and economic transition. The aim of this study was to identify total costs of treating patients with lumbar pain in medical facilities in the central part of the Republic of Serbia. MATERIAL AND METHODS: This study was designed as a cost of illness study, using a bottom-up approach and it was conducted from a societal perspective. This study included 97 patients with lumbar syndrome who were treated in outpatient facilities in the Central part of Serbia. RESULTS: Total costs of treating lumbar pain were about €200.40 ± €86.65 per patient per year, where the largest volume of direct costs were costs due to visits to specialists in primary health care institutions (€9.39 ± €6.66). Total indirect costs were €182.00 ± €78.66. DISCUSSION: Our findings highlight the need to estimate the total costs of treating lumbar pain and evaluate the correlation between costs and other variables for larger population of these patients. CONCLUSION: This study distinguished two important pharmacoeconomic aspects of treating lumbar pain. Firstly, indirect costs represent major part of total costs of treating lumbar syndrome. Secondly, differences in valuing medical services between countries with recent history of social and economic transition and countries within European Union are one of crucial reasons for difference in total costs of treating low back pain among patients in neighboring regions.

Introdução: As doenças crónicas incapacitantes têm um grande impacto fármaco-económico no orçamento da saúde, especialmente em países com alterações recentes a nível dos aspetos sociais e económicos. O objetivo deste estudo foi avaliar os custos do tratamento da dor lombar em unidades de saúde na região central da República da Sérvia. Material e Métodos: Este estudo foi realizado de forma a avaliar os custos da doença, com uma abordagem de baixo para cima e conduzido a partir de uma perspetiva social. O estudo incluiu 97 doentes com síndrome lombar tratados em ambulatório na região central da Sérvia. Resultados: O custo total do tratamento da dor lombar foi de €200.40 ± €86.65 por doente por ano, tendo os custos diretos de maior volume associados às consultas de especialidade em unidades de saúde de cuidados primários sido de €9,39 ± €6,66. O custo total indireto foi de €182,00 ± €78,66. Discussão: Do nosso estudo destaca-se a necessidade de estimar os custos totais do tratamento da dor lombar e de avaliar a correlação entre os custos e outras variáveis para maiores grupos de doentes. Conclusão: Este estudo faz a distinção entre dois importantes aspetos farmacoeconómicos no tratamento da dor lombar. Primeiro, os custos indiretos representam a maior parte dos custos totais no tratamento da síndrome lombar. Em segundo lugar, as diferenças na avaliação realizada nas unidades de saúde entre os países com alterações recente a nível dos aspetos sociais e económicos e os países da União Europeia são uma das principais razões para a diferença nos custos totais do tratamento da lombalgia entre doentes de regiões próximas.

What do humanitarian emergency organizations do about palliative care? A systematic review.

BACKGROUND: Humanitarian emergency organizations have only recently integrated care for non-communicable diseases into their relief action. The needs for palliative care in emergencies are still largely unmet. OBJECTIVE: A systematic review of health programmes run by international humanitarian organizations that take palliative care and/or enhanced pain control into account. METHODS: Electronic databases were searched for publications of health programmes providing palliative care and/or enhanced pain control in emergency situations. Health departments of major international organizations and experts were contacted for relevant information. RESULTS: One publication on pain treatment in amputees in Freetown, Sierra Leone, fulfilled the selection criteria. International humanitarian organizations shared information on their programmes in the Democratic Republic of the Congo, Haiti, Kenya and Ukraine/Russia. CONCLUSIONS: There is very little information available on palliative care and/or enhanced pain control in emergency settings. First programmes have just been initiated in the field. More emphasis on sharing experiences and publication could accelerate a broader integration of palliative care into humanitarian programmes.

Transdermal buprenorphine and fentanyl patches in cancer pain: a network systematic review.

Treatment of cancer pain is generally based on the three-step World Health Organization (WHO) pain relief ladder, which utilizes a sequential approach with drugs of increasing potency. Goals of pain management include optimization of analgesia, optimization of activities of daily living, minimization of adverse effects, and avoidance of aberrant drug taking. In addition, it is recommended that analgesic regimens are individualized and simplified to help ensure patient compliance and should provide the least invasive, easiest, and safest route of opioid administration to ensure adequate analgesia. Buprenorphine and fentanyl are two opioids available for the relief of moderate-to-severe cancer pain. Available clinical data regarding the transdermal (TD) formulations of these opioids and the extent to which they fulfill the recommendations mentioned earlier are systematically reviewed, with the aim of providing additional information for oncologists and pain specialists regarding their comparative use. Due to lack of studies directly comparing TD buprenorphine with TD fentanyl, data comparing these with other step-3 opioids are also evaluated in a network fashion.

[Multimorbidity management and the physician's daily clinical dilemma]. / Multimorbiditätsmanagement im Alltagsdilemma.

About 20-25% of all persons and about 90% of all patients who are acutely hospitalized in internal medicine departments have multiple acute or chronic diseases. They are multimorbid. The encounter with multimorbid patients has become the most common situation in the health care system. Theoretically, multimorbidity results in an innumerable potential disease constellations. In addition, the likelihood of interactions between diseases (disease-disease interactions, DDI) and the complexity increases overproportionately with each additional disease. However, multimorbidity often occurs in typical diadic, triadic, or higher characteristic combinations, in "disease clusters", e. g., vascular risk factors, heart and lung diseases, Frailty and dementia, psychiatric and somatic disorders. Such combinations lead to a worsening of the overall prognosis. In addition, DDIs are often difficult to treat or are life-threatening. Examples of DDIs include the following: anticoagulation and simultaneous severe bleeding, pain treatment and hypertension or renal insufficiency, depression and reduced medication adherence, chronic obstructive pulmonary disease and depression, Frailty and neurodepressant drugs and frequent falls, and combined psychiatric and somatic disorders. Such DDIs are common. Nevertheless, there are few studies and clinical guidelines that address these issues. The care of multimorbid patients is, therefore, heavily reliant upon guidelines developed mostly for single diseases. However, multimorbidity and serious DDIs are usually not addressed in these. Clinical guidelines can thus inadvertently jeopardize the safety of persons suffering from multiple diseases. In addition, stressful dilemmas arise for physicians encountering DDIs because of difficult treatment decisions.

Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong.

Opioids are increasingly used to control chronic non-cancer pain globally. International opioid guidelines have been issued in many different countries but a similar document is not generally available in Hong Kong. Chronic opioid therapy has a role in multidisciplinary management of chronic non-cancer pain despite insufficient evidence for its effectiveness and safety for long-term use. This document reviews the current literature to inform Hong Kong practitioners about the rational use of chronic opioid therapy in chronic non-cancer pain. It also aims to provide useful recommendations for the appropriate, effective, and safe use of such therapy in the management of chronic non-cancer pain in adults. Physicians should conduct a comprehensive biopsychosocial evaluation of patients prior to the commencement of opioid therapy. When opioid use is deemed appropriate, the patient should provide informed consent within an agreement that specifies treatment goals and expectations. A trial of opioid can be commenced and, provided there is progress towards treatment goals, then chronic therapy can be considered at a dose that minimises harm. Monitoring of effectiveness, safety, and drug misuse should be continued. Treatment should be stopped when opioids become ineffective, intolerable, or misused. The driving principles for opioid prescription in chronic pain management should be: start with a low dose, titrate slowly, and maintain within the shortest possible time.

[Specifics of Analgesia in Palliative Care Patients at Home]. / Spécificités de l'antalgie chez les patients palliatifs en situation ambulatoire.

Pain management at home for a patient, suffering from one or more advanced progressive diseases, goes beyond the prescription of an opioid. Apart from the importance of finding the most suitable analgesic drug (controlled pain with least possible adverse effects), three important dimensions will be addressed: interprofessionnal care (shared care goals, evaluation, monitoring of pain and other symptoms; physiotherapy, etc.) information, education and support for patients and relatives in particular on the use of opioids, and finally the importance of anticipation. This includes for example the requirement of breakthrough pain treatment in case of pain exacerbation or the definition of the place of hospitalization in case of worsening general condition or of death.

La prise en charge antalgique d'un patient atteint d'une ou plusieurs maladies évolutives avancées, à domicile, va bien au delà de la prescription d'un opioïde. Hormis l'importance de trouver l'antalgique le plus adapté (douleur contrôlée-moins d'effets indésirables possibles), trois dimensions seront évoquées: la prise en charge interprofessionnelle (objectifs de soins communs; évaluation-suivi de la douleur et des autres symptômes; physiothérapie, etc.), l'information, l'éducation et le soutien des patients et des proches en particulier sur l'utilisation des opiacés et finalement l'importance de l'anticipation. Celle-ci comprend par exemple la prescription des traitements de réserve en cas d'exacerbation douloureuse ou d'effets secondaires ou la définition du lieu d'hospitalisation en cas d'aggravation ou de décès.

Intrathecal injection of dexmedetomidine reduces neuropathic pain in rat model of chronic constriction injury / 中国医师杂志

Objective To investigate the effect of intrathecal injection (IT) of dexmedetomidine targeting Toll-like receptor 3 (TLR3) on neuropathic pain and spinal cord levels of TLR3 mRNA,interleukin-1β(IL-1β),tumor necrosis factor-alpha (TNF-α) proteins in rat model of chronic constriction injury (CCI).Methods Male Sprague-Dawley rats were randomly divided into five groups(n =10):the sham group(intrathecal normal saline,IT NS),CCI group (CCI + IT NS),DEX-pre group (CCI + IT DEX pre 2ds),DEX-post group (CCl + IT DEX post 7ds) and DEX + ATIP group (CCI + IT DEX + ATIP).The lumbar intrathecal catheters were implanted in L5_6 of rats and CCI models were established as previously described.The thermal and mechanical nociceptive thresholds were assessed by paw withdrawal latency(PWL) to radiant heat and yon Frey filaments.The DEX was administered intrathecally for 7 days starting from 2 day before surgery or 7day after surgery.The spinal cord expression of TLR3 mRNA was assessed by real-time polymerase chain reaction (PCR).Levels of IL-1β,TNF-α in spinal cord were detected by enzyme-linked immunosorbent assay (ELISA).Results Compared with the sham group,animals in CCI group had significandy lower mechanical (F =12.73,P ＜ 0.05) and thermal pain thresholds (F =14.65,P ＜ 0.05),higher expression of TLR3 mRNA (F =11.03,P ＜ 0.05) and levels of IL-1 β (F =9.67,P ＜ 0.05),TNF-α(F =8.78,P ＜ 0.05) in the spinal cord (P ＜ 0.05).Rats in DEX-pre group had significantly higher mechanical (F =11.03,P ＜ 0.05) and thermal pain thresholds (F =15.03,P ＜ 0.05) and significantly lower expression of TLR3 mRNA (F =14.65,P ＜0.05) and levels of IL-1β (F =12.51,P＜0.05,TNF-α (F =9.01,P ＜0.05) in the spinal cord compared with those in the CCI group (at any observed time points after ligation,but most significantly at 7 d).And the effects of DEX-pre group were abated by IT ATIP at the same time or 7days after surgery alone (P ＜ 0.05).Conclusions Intrathecal injection of DEX can decrease the levels of inflammatory factors by decreasing the TLR3 mRNA in the spinal cord of rats and prophylactic relieve the neuropathic pain induced by CCI.

The effect of lornoxicam on the expression of growth associated protein-43 and nerve growth factor in the dorsal root ganglion of rats during the development of neuropathic pain / 中国医师杂志

Objective To investigate the effect of lornoxicam on the.neurological behavior change and the expressions of growth associated protein-43 (GAP-43) and nerve growth factor (NGF) in dorsal root ganglion (DRG) on the peripheral nerve chronic constriction injury (CCI) model of rats.Methods Fifty Wistar rats were randomly divided into four groups:normal control group (n =5),CCI model group (CCI group),normal saline control group (NS group),and lomoxicam therapy group (L group) ; CCI,NS,and L groups were subdivided into 3 groups according to the different postoperative interval:3,7 and 14 days (n =5 each subgroup),respectively.The right sciatic nerve of rat was to be chronic constriction injure.Group L was given the rat 1.3 mg/kg of lomoxicam every 12 hours; then,the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of the rats of CCI,NS and L groups were measured at the different postoperative interval (3,7 and 14 days).After that,the DRG to the injured sciatic nerves were harvested.Immunohistochemistry was used to examine the expressions of GAP-43 and NGF.Results Comparing with the normal group,the latencies of MWT and TWL at CCI,NS and L groups were significantly declined at the third,seventh and fourteenth day after surgery (P ＜ 0.05),and the expressions of GAP-43 and NGF in DRG of CCI,NS and L groups were significantly increased after surgery (P ＜ 0.05).Comparing with the CCI group,the MWT and TWL of group L were significantly increased at the same time subgroup (P ＜ 0.05).The expressions of GAP-43 and NGF in DRG of group L were significantly declined at the same time subgroup (P ＜ 0.05).Conclusions Lornoxicam could relieve the symptoms of heat and mechanical hyperalgesia after sciatic nerve chronic constriction injury.It proved that lornoxicam was effective in the therapy of neuropathic pain.

Neuraxial (epidural and intrathecal) opioids for intractable pain.

1. Neuraxial opioids are considered for use in patients who have resistant intractable pain that fails to respond to other treatment options or pain that responds to analgesia but for which the doses required result in unacceptable side-effects. 2. Neuraxial opiods can be considered for both chronic non-malignant pain and chronic cancer-related pain. 3. Effectiveness in chronic non-malignant pain and cancer pain is exerted through the use of either single-agent drugs (opioids) or a combination of drugs: opioids, local anaesthetics and other drugs such as clonodine and ziconotide. 4. Complications of long-term continuous infusion therapy are related to the insertion process (haematoma), the mechanical device (both pump and catheter) and the long-term effects of the drugs. 5. Patients will require ongoing ambulatory monitoring and supportive care.

Management of cancer pain in community of Huanggu District of Shenyang City / 中华全科医师杂志

The status of anesthesia and psychotropic substances use for cancer pain control was analyzed in 355 cancer patients in Huanggu District of Shenyang City.The results revealed that patients aged 60 and above accounted for 62.8％ of the total; the 5 leading diseases were lung cancer ( 132 cases,37.2％ ),colorectal cancer (34 cases,9.6％ ),liver cancer (33 cases,9.3％ ),stomach cancer ( 31cases,8.7％ ) and pancreatic cancer (20 cases,5.6％ ).There was no significant difference in constituent ratio of disease categories in the last 4 years ( x2 =18.75,P ＞ 0.05 ).The daily oral dose of morphine sulphate was 60 - 200 mg with an effective rate of 91.5％ (325/355). The side effects including constipation,nausea,vomiting and itching can be effectively reduced by prophylactic medication.