The effects of clonidine and yohimbine in the tail flick and hot plate tests in the naked mole rat (Heterocephalus glaber)

Objective The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate the effects of clonidine and yohimbine, an alpha-2 (α2) adrenoceptor agonist and antagonist respectively in the tail flick and hot plate tests. Results A significant difference in tail flick latency was noted between saline control and 30 µg/kg clonidine, which was reduced after administration of 30 µg/kg yohimbine. A significant difference in hot plate latency was also noted between saline control and 30 µg/kg clodinine during the periods 30, 45, 60, 75 and 90 min after administration, and between saline control and 10 µg/kg clonidine during 30 min after administration. The hot plate latency by 30 µg/kg clonidine was also reduced by 30 µg/kg yohimbine during 30 min after administration. Since the tail-flick and hot plate tests mediate the effects at spinal and supraspinal levels respectively, the present study indicates the presence and involvement of noradrenergic receptors in thermal antinociception at spinal and supraspinal levels of the NMR, similar to what has been found in other mammals.

The effects of clonidine and yohimbine in the tail flick and hot plate tests in the naked mole rat (Heterocephalus glaber)

Objective: The naked mole rat (NMR) (Heterocephalus glaber) is increasingly considered an important biomedical research model for various conditions like hypoxic brain injury, cancer and nociception. This study was designed to investigate the effects of clonidine and yohimbine, an alpha-2 (α2) adrenoceptor agonist and antagonist respectively in the tail flick and hot plate tests. Results: A significant difference in tail flick latency was noted between saline control and 30µg/kg clonidine, which was reduced after administration of 30µg/kg yohimbine. A significant difference in hot plate latency was also noted between saline control and 30µg/kg clodinine during the periods 30, 45, 60, 75 and 90 minutes after administration, and between saline control and 10µg/kg clonidine during 30 minutes after administration. The hot plate latency by 30µg/kg clonidine was also reduced by 30µg/kg yohimbine during 30 minutes after administration. Since the tail-flick and hot plate tests mediate the effects at spinal and supraspinal levels respectively, the present study indicates the presence and involvement of noradrenergic receptors in thermal antinociception at spinal and supraspinal levels of the NMR, similar to what has been found in other mammals.

Study of analgesic property of diacerein in rat

Background: Diacerein has been known as an anti-osteoarthritic agent that is usually given along with other analgesic drugs. Still there is no evidence of the analgesic effect of diacerein alone. So this pilot study was undertaken to assess the analgesic property at supra-spinal level by using the tail-flick method.Methods: Diacerein at doses of 50, 100 and 200 mg/kg was given to Albino wistar rats weighing approximately 100-200 grams along with distilled water as placebo. All drugs were given by oral routes and the analgesic effect was evaluated using analgesiometer at baseline, 15 min, 30 min, 60 min and 120 min. Analgesic activity was measured as change in tail flick latency from baseline in animals.Results: Diacerein showed significant increase in tail flick latency and showed promising analgesic activity compared to placebo starting from 15 mins till 60 mins. However the effect persisted up to one hour only and after which it started decreasing.Conclusions: Diacerein at all the three doses possess dose dependant analgesic activity that is maximally effective up to 60 minutes.

A study to evaluate efficacy of Tinospora cordifolia (Guduchi) as analgesic agent using albino wistar rats as an experimental animal model

Background: Pain is a very well-known symptom of many diseases and analgesics are used to relieve pain. The main problem with these drugs remains that of side effects. Herbal medicines are better in view of their cultural acceptability, better compatibility with human body systems and lesser incidence of side effects. Extract of Tinospora cordifolia (Guduchi) plant have been traditionally used to treat pain in traditional medicine.Methods: Commercially available preparation of T. cordifolia plant has been used as test drug (aqueous extract). Healthy albino rats of either sex, weighing between 140-200 g were selected for the study, divided into 4 groups of 6 each (control, standard, 100 mg/kg, 300 mg/kg). Central analgesic activity was assessed by tail flick model (morphine as standard drug I.P). Acetic acid 1% 10 ml/kg aqueous solution I.P. was used for abdominal writhing model. Diclofenac 150 mg/kg oral as standard drug for assessment of peripheral analgesic activity. Results were analysed using SPSS version 16 and Microsoft office excel 2007.Results: T. cordifolia extract significantly increased the tail flick latency time (sec) (mean tail flick latency control, T100, T300 6.833±0.25 sec, 8.65±017 sec, 10.01±0.14 respectively) (p value control vs T100, T300 at 90 min, 120 min, 0.0573, 0.0198, 0.0198 in between group) and decreased number of abdominal writhing in comparison with the control group (p value <0.0001).Conclusions: Extract of T. cordifolia was found to possess analgesic activity and also exhibited dose and time dependant increase involving central and peripheral mechanisms. The analgesic activity of T. cordifolia found to be comparable to standard drug used.

Dynamics of nociceptive sensitivity in rats after melatonin treatment under normal conditions and during long-term stress exposure

Цель - изучение динамики ноцицептивной чувствительности крыс в разные временные периоды после внутрибрюшинного введения мелатонина (10 мг/кг) в условиях нормы и при однократной длительной стрессорной нагрузке на модели 24-ч иммобилизации. Результаты. Установлено, что введение мелатонина приводит к усилению перцептуального компонента ноцицепции животных, выраженность которого возрастает на протяжении 8 сут. наблюдений. На 3-и - 5-е сут. у этих особей выявлено возрастание порога вокализации в ответ на электрокожное раздражение, что иллюстрирует ослабление эмоционального компонента болевой чувствительности. Стрессорное воздействие сопровождалось снижением латентного периода реакции отведения хвоста при светотермальном раздражении, что наблюдалось сразу, а также через 1, 2 и 3 сут. после окончания стрессорного воздействия. В этих условиях увеличение порога вокализации крыс при электрокожной стимуляции обнаружено сразу после стрессорной нагрузки. Указанные изменения характеризуют усиление перцептуального компонента ноцицепции - формирование гипералгезии, но подавление эмоционального восприятия болевого раздражения на ранних стадиях постстрессорного периода. Показано, что экзогенный мелатонин не предупреждает развитие гипералгезии после 24-ч иммобилизации, однако подавляет эмоциональный компонент ноцицептивной чувствительности животных в отдаленный период после длительного стрессорного воздействия (4-е и 7-е сут.). Заключение. Применение мелатонина в целях коррекции измененной болевой чувствительности, при отрицательных эмоциогенных нагрузках, необходимо проводить с учетом временной стадии постстрессорного периода, а также принимая во внимание необходимость воздействия на перцептуальный или эмоциональный компонент ноцицепции. The dynamics of nociceptive sensitivity in rats was studied in various periods after intraperitoneal injection of melatonin (10 mg/kg) under normal conditions and during long-term stress exposure on the model of 24-h immobilization. Administration of melatonin was shown to enhance the perceptual component of nociception, whose degree progressively increased over 8 days of observations. The vocalization threshold of these specimens in response to electrocutaneous stimulation was elevated on days 3-5, which illustrates suppression of the emotional component of nociceptive sensitivity. Stress exposure in animals was accompanied by a decrease in the tail-flick latency during light-heat stimulation. It was observed immediately and 1, 2, and 3 days after termination of the stress procedure. An increase in the vocalization threshold of rats was found immediately after stress. These changes illustrate an enhancement of the perceptual component of nociception (hyperalgesia), but suppression of the emotional evaluation of pain stimulation at the early stage of the post-stress period. Exogenous melatonin did not prevent the development of hyperalgesia after 24-h restraint stress. However, melatonin inhibited the emotional component of nociceptive sensitivity in animals during the late period after long-term stress exposure (days 4 and 7). We conclude that the use of melatonin for correction of changes in nociceptive sensitivity due to negative emotiogenic factors should be performed taking into account the stage of the post-stress period and necessity to affect the perceptual or emotional component of nociception.

5-HT1A Receptors Mediate Analgesia Induced by Emulsified Sevoflurane in Thermal Nociception but Have Little Effect on Chemical Nociception

Objective: The study aimed to investigate the relationship between the analgesic effect of sevoflurane and 5-serotonin receptor 1A (5-HT1A R) in the spinal cords of mice. Methods: Analgesic mouse models were established by intraperitoneal injection of emulsified sevoflurane, and the influence of p-MPPF (a specific antagonist of 5-HT1A Rs) intrathecal injection on the changes in tail-flick latency in tail-withdrawal test, pain threshold in hot-plate test (HPPT), and writhing times in acetic acid-induced writhing test were recorded. Results: Intraperitoneal injection of emulsified sevoflurane alone produced an analgesic effect (p < 0.05). p-MPPF (2, 4, and 8 μg) alone had no impact on tail-flick latency, HPPT, and writhing times in mice (p > 0.05). The 3 doses of p-MPPF reduced the tail-flick latency or HPPT. p-MPPF 8 μg can increase the writhing times (p < 0.05) in analgesic mice with sevoflurane, while p-MPPF 2 and 4 μg did not affect the writhing times. Conclusion: 5-HT1A Rs in the spinal cord may be an important target for the analgesic effect of sevoflurane on the thermal nociception, but it has little relation to the anti-chemical chemical nociceptive effect of sevoflurane.

Standardization of Vyoshadi Saktu a Pathykalpana (Nutritional supplement) in Diabetes

Neuropathy and Cardiac complications are the most common trouble in diabetes mellitus with progressive damage due to complex pathogenesis. Many conventional pharmacological agents were withdrawn from clinical studies either due to lack of efficacy or due to side effects on major organs. Over the period of time traditional herbal plants were utilized in the treatment & management of diabetic complications. The aim of the present research work was to investigate efficacy and dynamics of Operculina turpethum root (OT) in STZ induced diabetic neuropathy and cardiac complications. Chronic treatment of crude extract of OT (500 mg/kg) showed positive effect in diabetic animals with significant reduction in blood glucose level, serum nitrite, brain homogenate nitrite & nerve homogenate nitrite levels as compared to diabetic control animals. Treatment with OT showed significant rise in body weight compared to Control animals & polyphagia were observed in diabetic animals persisted throughout the period of 8 weeks. Significant improvement was observed by treatment with OT in behavioural parameters like tail flick latency reduction and rise in pain threshold capacity. Nerve conduction velocity measured through BIOPAC system showed significant (P<0.05) improvement in diabetic animals, while improvement were observed in ECG profile, R-R interval, R wave amplitude, heart rate & cardiac hypertrophy index in diabetic animals when treated with OT. It was concluded from results that there is definite role of Operculina turpethum in the treatment and management of major diabetic complications.

Drug combinations in diabetic neuropathic pain: an experimental validation

Background:Diabetic neuropathy is the most common complication of diabetes mellitus, and the different drug combinations available do not provide effective pain relief. The present study was performed to observe the effect of amitripyline, duloxetine, sitagliptin, and pregabalin, and their combinations on streptozotocin (STZ)-induced diabetic neuropathy.Methods:Diabetic neuropathy was induced by STZ, and the tail-flick test was used to assess thermal hyperalgesia before and after (at 30, 60, and 120 min) drug administration. One week after STZ administration, the blood glucose level was observed to be in the diabetic range.Results:Administration of all the drugs except sitagliptin increased the tail-flick latency significantly as compared to control. Further, the drugs amitriptyline, duloxetine, and pregabalin showed significant pain-relieving effect, when either two of them were administered in combination, although the different combinations had varied degree of pain relief. However, sitagliptin was observed to have no effect when administered alone or in combination with the other three drugs.Conclusions:Therefore, the study provides new insights concerning combined therapy of pain, which further needs clinical exploration.

Membrane stabilizing, thrombolytic, analgesic, anti-diarrheal and CNS activities of Polyalthia longifolia (Sonn.)

Different fractions of Polialthia longifolia (Sonn.) bark were evaluated for membrane stabilizing, thrombolytic, analgesic, anti-diarrheal and CNS de-pressant activities upon oral administration at 200 and 400 mg/kg body weight. The membrane stabilizing activity was assessed by heat and hypo-tonic solution. Carbon tetrachloride fraction of methanol extract of P. longi-folia bark demonstrated strong membrane stabilizing activity, while the crude methanol extract demonstrated mild to moderate thrombolytic activi-ty in human blood specimen. The analgesic activity was assessed by tail im-mersion and formalin-induced pain method in Swiss-albino mice. The crude methanol extract of P. longifolia bark exhibited significant peripheral and central analgesic activity, since inhibited chemical induced writhing at 200 mg/kg and increased tail flick latency time both at 200 and 400 mg/kg. The anti-diarrheal activity of the bark extract was assessed by using castor oil induced diarrhea in mice however significant anti-diarrheal activity was not revealed. The CNS inhibitory activity of the methanol extract was assessed in Swiss albino mice where it reduced phenobarbitone sodium induced sleep-ing time at 400 mg/kg.