Neuronal GRK2 regulates microglial activation and contributes to electroacupuncture analgesia on inflammatory pain in mice

BACKGROUND: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. METHODS: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and down-regulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR. RESULTS: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain. CONCLUSION: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.

Comparison of granisetron and lidocaine on reducing injection pain of etomidate: a controlled randomized study / Comparação de granisetrona e lidocaína na redução da dor causada pela injeção de etomidato: estudo randômico e controlado

Abstract Background and objectives Reducing pain on injection of anesthetic drugs is of importance to every anesthesiologist. In this study we pursued to define if pretreatment by granisetron reduces the pain on injection of etomidate similar to lidocaine. Methods Thirty patients aged between 18 and 50 years of American Society of Anesthesiologists physical status class I or II, whom were candidates for elective laparoscopic cholecystectomy surgery were enrolled in this study. Two 20 gauge cannulas were inserted into the veins on the dorsum of both hands and 100 mL of normal saline was administered during a 10 min period from each cannula. Using an elastic band as a tourniquet, venous drainage of both hands was occluded. 2 mL of granisetron was administered into one hand and 2 mL of lidocaine 2% at the same time into the other hand. One minute later the elastic band was opened and 2 mL of etomidate was administered to each hand with equal rates. The patients were asked to give a score from 0 to 10 (0 = no pain, 10 = severe pain) to each the pain sensed in each hand. Results Two patients were deeply sedated after injection of etomidate and unable to answer any questions. The mean numerical rating score for injection pain of intravenously administered etomidate after intravenous granisetron was 2.3 ± 1.7, which was lower when compared with pain sensed due to intravenously administered etomidate after administration of lidocaine 2% (4.6 ± 1.8), p < 0.05. Conclusion The result of this study demonstrated that, granisetron reduces pain on injection of etomidate more efficiently than lidocaine.

Resumo Justificativa e objetivos A redução da dor causada pela injeção de anestésicos é importante para todos os anestesiologistas. Neste estudo buscamos definir se o pré-tratamento com granisetrona reduz a dor causada pela injeção de etomidato de forma semelhante à lidocaína. Métodos Trinta pacientes entre 18 e 50 anos, estado físico ASA I ou II (de acordo com a classificação da Sociedade Americana de Anestesiologistas) e candidatos à colecistectomia laparoscópica eletiva foram incluídos neste estudo. Duas cânulas de calibre 20 foram inseridas nas veias do dorso de ambas as mãos e 100 mL de soro fisiológico foram administrados durante 10 minutos através de cada cânula. Com um torniquete elástico, a drenagem venosa de ambas as mãos foi ocluída. Granisetrona (2 mL) foi administrado em uma das mãos e lidocaína a 2% (2 mL) na outra mão ao mesmo tempo. Após um minuto, o torniquete foi afrouxado e 2 mL de etomidato foram administrados em velocidade igual a cada uma das mãos. Solicitamos dos pacientes uma classificação de 0 a 10 para a dor sentida em cada uma das mãos (0 = sem dor, 10 = dor intensa). Resultados Dois pacientes estavam profundamente sedados após a injeção de etomidato e, portanto, incapazes de responder a qualquer pergunta. O escore médio de classificação da dor à injeção de etomidato administrado por via endovenosa após granisetrona intravenoso foi de 2,3 ± 1,7, o que foi menor em comparação com a dor sentida à administração intravenosa de etomidato após a administração de lidocaína a 2% (4,6 ± 1,8), p < 0,05. Conclusão O resultado deste estudo demonstrou que granisetrona reduz a dor causada pela injeção de etomidato com mais eficácia do que lidocaína.

Indução da dor pelo quimioterápico docetaxel em mulheres com câncer de mama / Pain induction by chemotherapy medication docetaxel in women with breast cancer

Resumo Objetivo Descrever a frequência, características, localização, intensidade da dor em pacientes com câncer de mama em uso do quimioterápico Docetaxel. Métodos Estudo longitudinal realizado com 17 mulheres com câncer de mama em tratamento com Docetaxel. As pacientes foram avaliadas durante três ciclos da quimioterapia quanto à dor, utilizando-se os instrumentos Questionário McGill de Dor (Br-MPQ) e Brief Pain Inventory (BPI). Utilizou-se a correlação de Spearman e o teste de Mann-Whitney. Resultados Houve aumento na média da dor em todas as variáveis do BPI. Quando comparados os valores do Pain Rating Index (PRI) total foram verificados respectivamente 0,20; 0,33 e 0,24 na primeira, segunda e terceira avaliações, sendo encontrada correlação entre a intensidade da dor e a interferência em todas as atividades do cotidiano no BPI na segunda avaliação. Conclusão Houve aumento na ocorrência da dor, comprometendo as atividades diárias de vida das mulheres participantes.

Abstract Objective To describe the frequency, characteristics, location, pain intensity in breast cancer patients using the chemotherapy medication Docetaxel. Methods Longitudinal study involving 17 women with breast cancer under treatment using Docetaxel. The patients’ pain was assessed during three chemotherapy cycles, using the tools McGill Pain Questionnaire (Br-MPQ) and the Brief Pain Inventory (BPI). Spearman’s correlation and the Mann-Whitney test were used. Results The mean pain score increased in all variables of the BPI. When comparing the total coefficients on the Pain Assessment Index, 0.20; 0.33 and 0.24 were found in the first, second and third assessment, showing a correlation between the pain intensity and the interference in all daily activities on the BPI for the second assessment. Conclusion The occurrence of pain increased, compromising the participating women’s activities of daily living.

Comparing the pain of propofol via different combinations of fentanyl, sufentanil or remifentanil in gastrointestinal endoscopy

PURPOSE: To evaluate the pain on injection of propofol via different combinations of fentanyl, sufentanil or remifentanil in gastrointestinal endoscopy. METHODS: Total 439 patients were randomly allocated into 6 groups. Propofol & fentanil (PF) group received 1 μg/kg fentanyl, propofol & sufentanil (PS) group received 0.1 μg/kg sufentanil and propofol & remifentanyl (PR) group received 1 μg/kg remifentanyl prior to administration of 1-2 mg/kg of propofol. The propofol & half-fentanil (Pf) group, propofol & half-sufentanil (Ps) group and propofol & half-remifentanyl (Pr) group were given 0.5 μg/kg fentanyl, 0.05 μg/kg sufentanil and 0.5 μg/kg remifentanyl, respectively and later administrated 1-2 mg/kg propofol. All patients were monitored for the blood pressure (MAP), heart rate (HR), and oxygen saturation (SpO2). Additionally, the pain intensity was assessed using a 4-point verbal rating scale (VRS) by professional doctors. RESULTS: The incidence of pain due to propofol injection in Ps group (33.8%) was significantly lower than other 5 groups. The heart rate (HR) and mean arterial pressure (MAP) were maintained within the normal limits in all six groups and there was no hypotension or bradycardia encountered during the study period. CONCLUSION: Propofol and sufentanil group was the most suitable program for painless gastroscopy. .

Ondansetron reducing pain on injection of etomidate: a controlled randomized study / Ondansetrona reduz a dor da injeção de etomidato: estudo randômico controlado / El ondansetrón reduce el dolor de la inyección de etomidato: estudio aleatorizado controlado

Introduction: Etomidate causes pain when injected intravenously. In this study we sought to determine if pretreatment by ondansetron reduces the pain on injection of etomidate. Methods: In this randomized, double blinded, placebo-controlled clinical trial, 20 patients of both sexes aged between 18 and 50 years of American Society of Anesthesiologists (ASA) physical status class I or II, whom were candidates for various elective surgical procedures and need more than one intravenous access were enrolled in the study. On arrival to the operating room two 22 gauge cannulas were inserted into veins on the dorsum of both hands. Following the infusion of 100 mL normal saline into both intravenous lines, using an elastic band, venous drainage of hands was occluded at midarm. The patients were administered 8 mg (2 mL) of ondansetron into one hand and 2 mL of 0.9% saline into the other hand at the same time. The elastic band was removed after 1 min and 2 mg (1 mL) of etomidate was administered at the same rate simultaneously into intravenous lines. The patients were asked to give a score of pain based on a verbal analog scale (VAS) to each hand. Results: A total number of 20 patients were studied (male = 55%, female = 45%). The mean age of the participants was 37.5 ± 13.1 years old and the mean weight was 67.7 ± 7.3 kg. The mean VAS for injection pain of etomidate after pre-administration of intravenous ondansetron was 1.5 ± 1.2 which was lower compared to pre-administration of placebo (3.2 ± 2.8, p < 0.05). Conclusion: This study illustrates that pre-treatment with intravenous ondansetron significantly reduces the pain on injection of etomidate. .

Justificativa e objetivo: etomidato causa dor quando administrado por via intravenosa. Neste estudo buscamos determinar se o pré-tratamento com ondansetrona reduz a dor causada pela injeção de etomidato. Métodos: neste estudo clínico randômico, duplo-cego e controlado por placebo, 20 pacientes de ambos os sexos, entre 18 e 50 anos, estado físico ASA I ou II, candidatos a procedimentos cirúrgicos eletivos que exigiam mais de um acesso intravenoso, foram incluídos. Ao darem entrada na sala de cirurgia, duas cânulas de calibre 22 foram inseridas nas veias do dorso de ambas as mãos. Após a infusão de 100 mL de solução salina normal em ambas as linhas de acesso intravenoso, a drenagem venosa das mãos foi ocluída até o meio do braço com o uso de um torniquete elástico. Os pacientes receberam 8 mg (2 mL) de ondansetrona em uma das mãos e 2 mL de solução salina a 0,9% na outra mão ao mesmo tempo. O torniquete foi removido após um minuto e 2 mg (1 mL) de etomidato foram administrados na mesma proporção simultaneamente nas linhas intravenosas. Pediu-se aos pacientes que dessem pontos à dor em cada mão, com base em uma escala verbal analógica (EVA). Resultados: avaliamos 20 pacientes (homens = 55%, mulheres = 45%). A média de idade e de peso foi de 37,5 ± 13,1 anos e 67,7 ±7,3 kg. A média do escore EVA para dor causada pela injeção de etomidato após a pré-administração de ondansetron IV foi de 1,5 ± 1,2, que foi menor em comparação com a pré-administração de placebo (3,2 ± 2,8, p < 0,05). Conclusão: este estudo mostra que o pré-tratamento com ondansetrona IV reduz significativamente a dor causada pela injeção de etomidato. .

Introducción: el etomidato causa dolor cuando es administrado por vía intravenosa. En este estudio buscamos determinar si el pretratamiento con ondansetrón reduce el dolor causado por la inyección de etomidato. Métodos: fueron incluidos en este estudio clínico aleatorizado, doble ciego y controlado por placebo, 20 pacientes de ambos sexos con edades entre 18 y 50 años, estado físico ASA I o II, candidatos a varios procedimientos quirúrgicos electivos, que exigían más de un acceso intravenoso. Al entrar en quirófano, se insertaron dos cánulas de calibre 22 en las venas del dorso de ambas manos. Después de la infusión de 100 mL de solución salina normal en ambas líneas de acceso intravenoso; usando un torniquete elástico, el drenaje venoso de las manos se cerró hasta la mitad del brazo. Los pacientes recibieron 8 mg (2 mL) de ondansetrón en una de las manos y 2 mL de solución salina al 0,9% en la otra mano al mismo tiempo. El torniquete fue retirado después de 1 min y 2 mg (1 mL) de etomidato se administró en la misma proporción simultáneamente en las líneas intravenosas. Se les solicitó a los pacientes que hiciesen una puntuación del dolor en cada mano, basándose en una escala verbal analógica (EVA). Resultados: evaluamos a un total de 20 pacientes (un 55% hombres y un 45% mujeres). La media de edad y del peso de los participantes fue de 37,5 ± 13,1 años y de 67,7 ±7,3/kg, respectivamente. El promedio de la puntuación EVA para el dolor causado por la inyección de etomidato después de la preadministración de ondansetrón iv fue de 1,5 ± 1,2, siendo menor en comparación con la preadministración de placebo (3,2 ± 2,8; p < 0,05). Conclusión: este estudio demuestra que el pretratamiento con ondansetrón iv reduce ...

Epidural Dexamethasone Decreased Inflammatory Hyperalgesia and Spinal cPLA2 Expression in a Rat Formalin Test

PURPOSE: The aim of this study was to investigate the effect of epidural dexamethasone on analgesia and cytosolic phospholipase A2 (cPLA2) expression in the spinal cord in a rat formalin test. MATERIALS AND METHODS: Epidural dexamethasone injection was performed to Sprague-Dawley rats with a 25 gauge needle under fluoroscopy. Following the epidural injection, a formalin induced pain behavior test was performed. Next, the spinal cords corresponding to L4 dorsal root ganglion was extracted to observe the cPLA2 expression. RESULTS: There were no differences in pain response during phase I among the groups. The phase II pain response in 300 microg of epidural dexamethasone group decreased as compared to control, 30 microg of epidural dexamethasone, 100 microg of epidural dexamethasone, and 300 microg of systemic dexamethasone groups. The expression of cPLA2 decreased in Rexed laminae I-II in 300 microg of the epidural dexamethasone group compared with the ones in the control group. CONCLUSION: Taken together, these results suggest that 300 microg of epidural dexamethasone has an attenuating effect on the peripheral inflammatory tissue injury induced hyperalgesia and this effect is mediated through the inhibition of intraspinal cPLA2 expression and the primary site of action is the laminae I-II of the spinal cord.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties.

Sclerotherapy of hydroceles and spermatoceles with alcohol: results and effects on the semen analysis

PURPOSE: To evaluate the success rates of sclerotherapy of the tunica vaginalis with alcohol for the treatment of hydroceles and/or spermatoceles, as well as, evaluation of pain, formation of hematomas, infection and its effects in spermatogenesis . MATERIALS AND METHODS: A total of 69 patients, with offsprings and diagnosis of hydrocele and/or spermatocele, were treated during the period from April 2003 to June 2007. Semen analysis was obtained from patients who were able to provide us with samples. The sclerotherapy with alcohol at 99.5 percent was undertaken as outpatient procedure. RESULTS: The average volume drained pre-sclerotherapy was 279.82 mL (27 to 1145). The median follow-up was 43 months (9 to 80). A total of 114 procedures were performed on 84 units, with an average of 1.35 procedures / unit and an overall success rate of 97.62 percent. Of the 69 patients, 7 (10.14 percent) reported minor pain immediately after the procedure, 3 (4.35 percent) moderate pain and 2 (2.89 percent) intense pain. Post-Sclerotherapy spermograms revealed reduction of the parameters regarding: concentration, motility and morphology up to 6 months post procedure , with return to normal parameters 12th months after procedure. CONCLUSIONS: Sclerotherapy of hydroceles and spermatoceles with 99.5 percent alcohol is an efficient procedure that can be perormed without difficulties, cost-effectiveness, with few side effects and which may be performed in patients who wish fertility.

Effect of glibenclamide on antinociceptive effects of antidepressants of different classes

OBJECTIVES: The purpose of this work was to determine whether the intraperitoneal administration of glibenclamide as a K ATP channel blocker could have an effect on the antinociceptive effects of antidepressants with different mechanisms of action. METHODS: Three antidepressant drugs, amitriptyline as a dual-action, nonselective inhibitor of noradrenaline and a serotonin reuptake inhibitor, fluvoxamine as a selective serotonin reuptake inhibitor and maprotiline as a selective noradrenaline reuptake inhibitor, were selected, and the effect of glibenclamide on their antinociceptive activities was assessed in male Swiss mice (25-30 g) using a formalin test. DISCUSSION: None of the drugs affected acute nociceptive responses during the first phase. Amitriptyline (5, 10 mg/ kg), maprotiline (10, 20 mg/kg) and fluvoxamine (20 and 30 mg/kg) effectively inhibited pain induction caused by the second phase of the formalin test. Glibenclamide (5 mg/kg) alone did not alter licking behaviors based on a comparison with the control group. However, the pretreatment of animals with glibenclamide (10 and 15 mg/kg) partially reversed the antinociceptive effects of fluvoxamine but not those of maprotiline. In addition, the highest dose of glibenclamide (15 mg/kg) partially prevented the analgesic effect of amitriptyline. CONCLUSION: Therefore, it seems that adenosine triphosphate-dependent potassium channels have a major role in the analgesic activity of amitriptyline and fluvoxamine.

Hip pain and retinoids [Isotretinoin]

The retinoids are classes of chemical compounds that are related chemically to vitamin A. Retinoids are used in medicine, primarily due to the way they regulate epithelial cell growth. Retinoids are used in the treatment of many diverse diseases and are effective in the treatment of a number of dermatological conditions such as inflammatory skin disorders, skin cancers, disorders of increased cell turnover e.g. psoriasis and photo aging. Common skin conditions treated by retinoids include acne and psoriasis. These compounds being widely used have serious documented side effects including myalgia and arthralgia. We present a case where an 18 years male patient was given Isotretinoin a higher generations of retinoid, for his acne and after taking it for three days he presented in emergency department with severe hips pain, unable to stand and walk. This case has indicated that hip pain can be a result of a side effect of retinoids and its derivatives or new generation of retinoids

single-centre randomized-controlled trial to study effect of dilution on propofol-induced injection pain at injection site

Propofol is a commonly used short-acting intravenous anaesthetic agent. A major disadvantage of propofol is pain at injection site with high incidence up to 90%. Various modalities have been tried to obtund propofol-induced pain; however, search for an ideal agent continues. We assessed the effect of double and triple dilution of 1% propofol emulsion with normal saline on pain at injection site. This randomized, double-blinded study was done on 60 adult patients of both sexes, belonging to ASA grade I and II scheduled for elective surgery under general anesthesia, divided into three groups named I, II, III of 20 patients each. The patients of group I, II, and III received 1% propofol 2 ml, 0.5% propofol 4 ml, and 0.33% propofol 6 ml, respectively, over a period of 4 s and pain felt was assessed. There was no statistically significant difference in the pain score in group II as compared to patients in group I. However, there was a statistically significant decrease in the pain score in group III as compared to patients in group I [P value 0.02] and group II [P value 0.03]. Conclusions: We found a significant decrease in both incidence and severity of pain during injection with a 0.33% propofol solution without significant adverse hemodynamic effects. The small size of data was a limitation in our study and a large-scale study will be needed to prove its therapeutic beneficence

Investigation of a one-time phenol application for pilonidal disease

To investigate wound healing rates and postoperative recovery of patients after a one-time phenol application for pilonidal disease. A total 30 consecutive patients with chronic pilonidal disease ranging from midline to complex sinuses were enrolled in the study. No preoperative laboratory examinations or bowel preparation were required. No antibiotic prophylaxis or sedation was used. A small incision was made on the midline and hair/ debris in the sinuses was removed. A cotton swab with saturated phenol was moved into the cavity and the phenol was left for 2 min. No special dressing was necessary and patients left the hospital immediately afterwards. Patients filled out a daily questionnaire for 7 days. We did not intervene in the wounds with a second phenol application or curettage during the observation period. Wounds were inspected at weekly intervals for 2 months. At the end of the third day, 97% of the patients were pain-free and 100% of the patients were free from analgesics. Time off work was 2 days for most patients [93.3%]. Twenty-eight [93.3%] patients were satisfied with the procedure, they found it easy and painless and suggested the procedure to other patients. Twenty-five [83%] patients were asymptomatic at the end of 2 months' observation and the remaining 5 patients had un-healed sinuses. Mean time for wound healing was 25 days [range 10-63 days]. There were 4 recurrences after a mean of 14 months' follow-up and the overall success rate was 70%. A one-time phenol application was an effective treatment for pilonidal disease with acceptable wound healing rates, less postoperative pain and less time off work. Hence it can be an alternative treatment modality

Efeito analgésico de antagonistas do receptor da histamina H1 em modelo de dor provocada por formalina em ratos / Efecto analgésico de antagonistas del receptor de la histamina H1 en un modelo de dolor provocado por formalina en ratones / Analgesic effects of H1 receptor antagonists in the rat model of formalin-induced pain

JUSTIFICATIVA E OBJETIVOS: Os receptores de histamina mediam vias nociceptivas principalmente no sistema nervoso central. Alguns estudos mostraram efeito analgésico de antagonistas de receptor de histamina no sistema nervoso periférico. Não está claro se o efeito analgésico local é classe específico ou droga específico. MÉTODO: Para responder a essa questão, utilizamos três diferentes antagonistas do receptor H1 (pirilamina, prometazina e cetirizina) administrados diretamente na pata do rato, pela via intraperitoneal ou por bloqueio de nervo periférico em modelo de dor induzida por formalina. Observamos o efeito das drogas no comportamento do número de elevações da pata. RESULTADOS: Na fase I, a pirilamina local diminuiu o número de elevações da pata de forma dose-dependente. Na dose mais alta, a diminuição foi de 97,8 por cento. Para a prometazina, a diminuição foi de 92 por cento e para cetizirina, 23,9 por cento. Na fase II, a pirilamina diminuiu o número de elevações da pata em 93,5 por cento, a prometazina em 78,2 por cento e a cetirizina em 80,1 por cento. A administração dos fármacos por via intraperitoneal não alterou o comportamento doloroso. Quando utilizadas para bloqueio de nervo periférico, na fase I, a pirilamina diminuiu o número de elevações da pata em 96,7 por cento, a prometazina em 73,3 por cento e a cetirizina em 23,9 por cento. Na fase II, a pirilamina levou à diminuição de 86,6 por cento, a prometazina de 64,4 por cento e a cetirizina de 19,9 por cento. CONCLUSÕES: Os resultados mostraram que os antagonistas de receptor da histamina H1 apresentam efeitos analgésicos locais, diferentes do efeito sistêmico, sendo um deles anti-inflamatório e classe específico e o outro específico para prometazina e pirilamina, semelhante a efeito clínico anestésico local.

BACKGROUND AND OBJECTIVES: Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific. METHODS: To answer this question, we used three different H1 receptor antagonists (pyrilamine, promethazine, and cetirizine) administered directly in the paw of the rat, intraperitoneally, or in peripheral nerve blockade in the formalin-induced pain model. The effects of the drugs on the number of paw elevations were observed. RESULTS: In phase I, the local administration of pyrilamine caused a dose-dependent reduction on the number of paw elevations; in the highest dose, the number of paw elevations was reduced by 97.8 percent. Promethazine decreased it by 92 percent, while cetirizine decreased by 23.9 percent. In phase II, pyrilamine decreased the number of paw elevations by 93.5 percent, promethazine by 78.2 percent, and cetirizine by 80.1 percent. Intraperitoneal administration of drugs did not change painful behavior. When used in peripheral nerve block, in phase I pyrilamine reduced the number of paw elevations by 96.7 percent, promethazine by 73.3 percent, and cetirizine by 23.9 percent. In phase II, pyrilamine reduced the number of paw elevations by 86.6 percent, promethazine by 64.4 percent, and cetirizine by 19.9 percent. CONCLUSIONS: The results demonstrate that H1 receptor antagonists have local analgesic effects, different from the systemic effects, one of them an anti-inflammatory and class-specific effect and the other similarly to the local anesthetic effect, specific for promethazine and pyrilamine

JUSTIFICATIVA Y OBJETIVOS: Los receptores de histamina intermedian las vías nociceptivas, principalmente en el sistema nervioso central. Algunos estudios arrojaron un efecto analgésico de antagonistas de receptor de histamina en el sistema nervioso periférico. No queda claro si el efecto analgésico local es de clase específico o un fármaco específico. MÉTODO: Para responder a esa pregunta, utilizamos tres diferentes antagonistas del receptor H1 (pirilamina, prometazina y cetirizina), administrados directamente en la pata del ratón, por vía intraperitoneal o por bloqueo de nervio periférico en modelo de dolor inducido por formalina. Observamos el efecto de los fármacos en el comportamiento del número de elevaciones de la pata. RESULTADOS: En la fase I, la pirilamina local redujo el número de elevaciones de la pata de forma dosis dependiente. En la dosis más alta, la reducción fue de un 97,8 por ciento. Para la prometazina, la disminución fue de un 92 por ciento y para la cetizirina de 23.9 por ciento. En la fase II, la pirilamina redujo el número de elevaciones de la pata en un 93,5 por ciento, la prometazina, un 78,2 por ciento y la cetirizina un 80,1 por ciento. La administración de los fármacos por vía intraperitoneal no alteró el comportamiento doloroso. Cuando se usaron para bloqueo del nervio periférico en la fase I, la pirilamina redujo el número de elevaciones de la pata en un 96,7 por ciento, la prometazina en un 73,3 por ciento y la cetirizina en un 23,9 por ciento. En la fase II, la pirilamina redujo un 86,6 por ciento, la prometazina un 64,4 por ciento y la cetirizina un 19,9 por ciento. CONCLUSIONES: Los resultados mostraron que los antagonistas del receptor de la histamina H1 presentaron efectos analgésicos locales, diferentes del efecto sistémico, siendo uno de ellos antiinflamatorio y clase específico, y el otro específico para la prometazina y la pirilamina, parecido con el efecto clínico anestésico local.

Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection.

Nicolau syndrome following intramuscular benzathine penicillin.

Nicolau syndrome (NS) is a rare complication of an intramuscular injection characterized by severe pain, skin discoloration, and varying levels of tissue necrosis. The case outcomes vary from atrophic ulcers and severe pain to sepsis and limb amputation. We describe a case of a seven-year-old boy with diagnosis of NS after intramuscular benzathine penicillin injection to the ventrolateral aspect of the left thigh. Characteristic violaceous discoloration of skin and immediate injection site pain identified it as a case of NS. The case was complicated by rapid progression of compartment syndrome of the lower limb, proceeding to acute renal failure and death. Associated compartment syndrome can be postulated as a poor prognostic factor for NS.

Efeito analgésico local do tramadol em modelo de dor provocada por formalina em ratos / Local effect of tramadol on formalin evoked flinching behavior in rats / Efecto analgésico local del tramadol en modelo de dolor provocado por formalina en ratones

JUSTIFICATIVA E OBJETIVOS: O cloridrato de tramadol é um fármaco analgésico de ação central, utilizado no tratamento de dores moderadas e intensas. Foi demonstrado efeito analgésico local do tramadol, mas seu mecanismo de ação não foi estabelecido. MÉTODO: Estudou-se o efeito da administração local, sistêmica e por bloqueio de nervo periférico do tramadol sobre o comportamento de elevação da pata gerado pela injeção de 50 µL de formalina a 1 por cento na região dorsal da pata de ratos. O número de elevações da pata foi observado pelo período de 60 minutos. RESULTADOS: A administração local de tramadol em concentrações maiores (2,5 e 5 mg) levou ao bloqueio praticamente completo do comportamento de elevação da pata durante todo o teste. A administração sistêmica e por bloqueio de nervo periférico não afetou o comportamento de elevação da pata na fase I e diminuiu parcialmente na fase II. CONCLUSÕES: O tramadol apresentou efeito analgésico local no modelo de comportamento de elevações da pata com formalina, que é diferente de sua ação central. Esse efeito, nesse modelo, não parece ser ligado a efeito anestésico local.

BACKGROUND AND OBJECTIVES: Tramadol hydrochloride is known as a centrally acting analgesic drug, used for the treatment of moderate to severe pain. A local analgesic effect has been demonstrated, but its mechanism of action remains unclear. METHODS: In this study, we examined the effect of local, systemic and nerve block tramadol on the nociceptive flinching behavior elicited by injection of 50 µL of 1 percent formalin into the dorsal region of hind paw of rats. Nociceptive flinching behavior was observed for 60 minutes. RESULTS: Local tramadol in higher concentrations (2.5 and 5mg) almost eliminated flinching behavior during the entire test. Systemic and neural block tramadol did not affect flinching behavior in phase I and partially decreased it in phase II. CONCLUSIONS: Tramadol presented a local analgesic effect in formalin nociceptive flinching behavior that is different from its central analgesic effect. This analgesic effect, in this model, seems not to be linked to a local anesthetic like effect.

JUSTIFICATIVA Y OBJETIVOS: El clorhidrato de tramadol es un fármaco analgésico de acción central, utilizado en el tratamiento de dolores moderados e intensos. Quedó demostrado un efecto analgésico local del tramadol, pero su mecanismo de acción no fue establecido. MÉTODO: Se estudió el efecto de la administración local, sistémica y por bloqueo de nervio periférico del tramadol sobre el comportamiento de elevación de la pata generado por la inyección de 50 µL de formalina a 1 por ciento en la región dorsal de la pata de los ratones. El número de elevaciones de la pata fue observado durante 60 minutos. RESULTADOS: La administración local de tramadol en concentraciones mayores (2,5 y 5 mg) conllevó al bloqueo prácticamente completo del comportamiento de elevación de la pata durante todo el test. La administración sistémica y por bloqueo de nervio periférico, no afectó el comportamiento de elevación de la pata en la fase I y se redujo parcialmente en la fase II. CONCLUSIONES: El tramadol presentó un efecto analgésico local en el modelo de comportamiento de elevaciones de la pata con formalina, que es diferente de su acción central. Ese efecto, en ese modelo, no parece estar vinculado al efecto anestésico local.

Additive Antinociception between Intrathecal Sildenafil and Morphine in the Rat Formalin Test

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 microliter of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.

Sclerotherapy of idiopathic hydroceles and epididymal cysts: a historical comparison trial of 5% phenol versus tetracycline

Operating time for idiopathic hydroceles and epididymal cysts is scarce as these conditions compete with an increasing caseload of more consequential surgical disease. Therapy is often relegated to repeated aspiration. Sclerotherapy appears to be effective in a majority of published trials, but comparative effectiveness, efficacy and safety of most agents, including phenol versus tetracycline, has not been established A deliberate strategy of re-treatment until cure is not universally practised, with surgery still being offered after single-treatment failures. Two trials, the first consisting of 53 scrotal cysts treated with 5% phenol-in-water and the second, 42 cysts treated with tetracycline, are compared for effectiveness, efficacy and safety of sclerotherapy per se and of re-treatment. Intention-to-treat analysis yields similar cure rates (no re-accumulation three months after last injection) for phenol and tetracycline (83% and 81% respectively, p = 0.8). Per-protocol analysis also yields similar cure rates (100% and 97% respectively, p = 0.26) and mean number of injections to cure (1.34 and 1.12 respectively, p = 0.069), with range 1-4 and 1-3 respectively. Severe pain following tetracycline injection required administration of pre-injection cord block. Other complications occurred equally (25% and 25.7% respectively, p = 0.94) and were trivial except for one case of chronic haematocele treated by orchiectomy in the tetracycline group. Phenol (5%) and tetracycline are equally efficacious sclerosants for idiopathic scrotal cysts, achieving almost 100% cure with re-treatment and matching the efficacy of surgery. Concern about post-treatment fertility applies equally to surgery and demands informed consent for both modalities.

El tiempo de operación para los hidroceles y los quistes epididimales es escaso, ya que estas condiciones triviales compiten con una creciente carga de casos de enfermedades quirúrgicas de mayores consecuencias. La terapia es a menudo relegada a una aspiración repetida. La escleroterapiaparece ser efectiva en la mayoría de los ensayos publicados, pero no se han establecido la seguridad, eficacia y efectividad comparativa de la mayor parte de los agentes, incluyendo el fenol, frente a la tetraciclina. No se practica universalmente una estrategia deliberada de re-tratamiento hasta la cura, ofreciéndose todavía la cirugía, luego de fracasos con tratamientos individuales. Dos ensayos, el primero consistente en 53 quistes escrotales tratados con fenol acuoso al 5%, y el segundo, en 42 quistes tratados con tetraciclina, se comparan en cuanto a efectividad, eficacia y seguridad para laescleroterapia per se y para el re-tratamiento. El análisis de intención de tratamiento produce tasas de curación similares (no hay re-acumulación 3 meses después de la última inyección) para el fenol y la tetraciclina (83% y 81% respectivamente, p = 0.8). El análisis por protocolo también produce tasas de curación similares (100% y 97% respectivamente, p = 0.26) y el número medio de inyecciones paracurar (1.34 y 1.12 respectivamente, p = 0.069), con rangos de 1–4 y 1–3 respectivamente. El dolor severo tras la inyección de tetraciclina requirió hacer un bloqueo espinal de pre-inyec-ción. Asimismo ocurrieron otras complicaciones (25% y 25.7% respectivamente, p = 0.94) y fueron triviales, con excepción de un caso de hematoceles crónicos tratado mediante orquiectomía en el grupo de tetraciclina. El fenol (5%) y la tetraciclina poseen igual eficacia como esclerosantes de los quistes escrotales idiopáticos, ya que logran una curación de casi 100% con el re-tratamiento, e igualan la eficacia de la cirugía...

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Comparison on pain on injection of a small particle size-lipid emulsion of propofol and standard propofol with or without lidocaine.

Pain on injection, reported in 28-90% of patients, is one of the most described side effects of the intravenous application of propofol. Many different approaches have been used in attempts to minimize propofol induced pain, with varied results. Using a randomized, double-blind protocol design, the author-section pain following the administration of two different particle size formulations of propofol with or without lidocaine in 388 nonpremedicated ASA I-II adult patients scheduled for elective surgery under general anesthesia. Patients were allocated randomly to receive either a small particle size lipid emulsion of propofol (Anepol: average particle size 140.5 nm), or standard propofol (Propofol: average particle size 193.3 nm), by dividing into 4 groups. Group 1 received 2 ml NaCl 0.9% and Propofol, group 11 received 2 ml lidocaine 2% and Propofol, group III received 2 ml NaCl 0.9% and Anepol and group IV received 2 ml lidocaine 2% and Anepol into a dorsal vein of the hand. Pain during propofol injection was evaluated over 5-10 seconds, until loss of conscious, using a four point scale. Sixty-seven patients (69.1%) complained of pain in group 1, as compared with 50%, 41.2% and 39.2% in group II, III and IV (p < 0.05). The reported severity of injection pain was not significantly different between the groups. The authors conclude that small particle size propofol causes less pain on injection than standard propofol.