Antihyperalgesic and Side Effects of Intrathecal Clonidine and Tizanidine in a Rat Model of Neuropathic Pain

2003 ◽  
Vol 98 (6) ◽  
pp. 1480-1483 ◽  
Author(s):  
Tomoyuki Kawamata ◽  
Keiichi Omote ◽  
Hiroki Yamamoto ◽  
Masaki Toriyabe ◽  
Kohsuke Wada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Neuropathic Pain ◽  
Side Effects ◽  
Rat Model ◽  
Animal Studies ◽  
Intrathecal Administration ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Intrathecal Clonidine

Background Although intrathecal clonidine produces pronounced analgesia, antinociceptive doses of intrathecal clonidine produce several side effects, including hypotension, bradycardia, and sedation. Intrathecal tizanidine, another alpha(2)-adrenergic agonist, has provided antinociception without producing pronounced hemodynamic changes in animal studies. However, it has been unclear whether antihyperalgesic doses of intrathecal clonidine and tizanidine produce hypotension and bradycardia in a neuropathic pain state. This study was designed to evaluate the antihyperalgesic effects and side effects of intrathecal clonidine and tizanidine in a rat model of neuropathic pain. Methods Male Sprague-Dawley rats were chronically implanted with lumbar intrathecal catheters, and the sciatic nerve was loosely ligated. After 21-28 days after surgery, the rats received intrathecal clonidine (0.3, 1.0, and 3.0 microg) and tizanidine (1.0, 2.0, and 5.0 microg), and the antihyperalgesic effects of thermal and mechanical stimuli were examined. In addition, the changes in blood pressure and heart rate, sedation level, and other side effects after intrathecal administration of drugs were recorded. Results The administration of 3.0 microg intrathecal clonidine or 5.0 microg tizanidine significantly reversed both thermal and mechanical hyperalgesia. The administration of 3.0 microg intrathecal clonidine, but not 5.0 microg tizanidine, significantly decreased mean blood pressure and heart rate and produced urinary voiding. A greater sedative effect was produced by 3.0 microg intrathecal clonidine than by 5.0 microg tizanidine. Conclusion The antihyperalgesic dose of intrathecal clonidine and the antinociceptive doses produced several side effects. Intrathecal tizanidine at the dose that reversed hyperalgesia would be preferable for neuropathic pain management because of absence of hypotension and bradycardia and lower incidence of sedation.

Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin

1990 ◽  
Vol 68 (2) ◽  
pp. 174-182 ◽  
Author(s):  
J. A. Thornhill ◽  
Q. J. Pittman
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arginine Vasopressin ◽  
Cardiovascular Responses ◽  
Intrathecal Administration ◽  
Opioid Antagonist ◽  
Sprague Dawley ◽  
Dynorphin A ◽  
Hemodynamic Responses ◽  
Conscious Rats

Experiments were conducted (i) to determine the hemodynamic (blood pressure and heart rate) responses of conscious rats following intrathecal (IT) administration of endogenous prodynorphin-derived opioids into the lower thoracic space, (ii) to identify the receptors involved in mediating their cardiovascular responses, and (iii) to reveal any possible hemodynamic interactions with the neuropeptide arginine vasopressin. Male Sprague–Dawley rats were surgically prepared with femoral arterial and venous catheters as well as a spinal catheter (into lower thoracic region, T9–T12). After recovery, hemodynamic responses were observed in conscious rats for 5 – 10 min after IT injections of artificial cerebrospinal fluid (CSF) solution, prodynorphin-derived opioids (dynorphin A, dynorphin B, dynorphin A (1 – 13), dynorphin A (1 – 10), α- and β-neoendorphin, leucine enkephalin (LE), methionine enkephalin (ME), arginine vasopressin (AVP), or norepinephrine (NE)). IT injections of AVP (10 or 20 pmol), dynorphin A (1 – 13), or dynorphin A (10 – 20 nmol) caused pressor effects associated with a prolonged and significant bradycardia. Equimolar (20 nmol) concentrations of LE, ME, α- and β-neoendorphin, and dynorphin A (1 – 10) caused no significant blood pressure or heart rate changes. Combined IT injections of dynorphin A (1 – 13) and AVP caused apparent additive pressor effects when compared with the same dose of either peptide given alone. IT infusion of the specific AVP–V1 antagonist d(CH2)5Tyr(Me)AVP before subsequent IT AVP, dynorphin A (1 – 13), or NE administration inhibited only the subsequent pressor responses to AVP. The x-opioid antagonist (Mr2266) infused IT blocked the pressor actions of subsequent dynorphin A administration and not AVP or NE. These results indicate that dynorphin A and dynorphin A (1 – 13), in the doses used, given IT to conscious rats evoked pressor and bradycardic responses. The pressor actions of dynorphin A appear to be mediated by spinal x-opioid receptors and are independent of interaction with spinal AVP–V1 receptors.Key words: prodynorphin-derived peptides, arginine vasopressin, intrathecal administration, hemodynamic effects, specific receptor-mediated responses.

Abstract 119: Influence of Anesthetics on the Hemodynamic Response in a Rat Model of Hemorrhagic Shock

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz J Baudenbacher ◽  
Susan S Eagle ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hemorrhagic Shock ◽  
Rat Model ◽  
Cardiovascular Response ◽  
Femoral Vein ◽  
Blood Pressure Measurement ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Compensatory Mechanisms ◽  
Arterial Blood

Introduction: Experimental models of hemorrhagic shock (HS) in rats are important to test new treatments that may improve outcomes in humans, and general anesthesia is required during these experiments. The volatile anesthetic Isoflurane is known for its beneficial effects in rat HS models. Focusing on cardiovascular compensatory mechanisms, we wanted to evaluate Isoflurane versus the injectable anesthetic Pentobarbital in our rat model of mild HS (class 2). We hypothesize that Isoflurane during development of HS improves hemodynamics compared to Pentobarbital. Methods: Twelve Sprague-Dawley rats were initially anesthetized with an intraperitoneal (IP) injection of Pentobarbital (45 mg/kg) and intubated (1 L/min, FiO 2 0.25); heart rate (HR) was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids, respectively. In one group (n=7), anesthesia was continued with repeated IP injections of Pentobarbital (dose mg/kg), the other group (n=5) received continuous Isoflurane (1%). After 30 min of stabilization and administration of Heparin (100 IU/kg), HS was induced by removal of 1 ml of blood over 1 min via the femoral vein, repeated every 3 min until a volume of 5 ml of blood was removed. Mean arterial blood pressure (MAP) and HR were recorded and analyzed in LabChart. Results: During baseline, rats showed no significant differences in HR and MAP between both groups. After 5 ml of hemorrhage, both groups showed significant changes compared to baseline, with significantly higher MAP and HR in rats given only Pentobarbital. Conclusions: In our rat model of HS, Isoflurane dampens the physiologic response to compensate for mild hemorrhage. The cardiovascular response of rats in the Isoflurane group was a decrease of HR and MAP to every ml of hemorrhage, while rats given only Pentobarbital were able to maintain their MAP by raising their HR until decompensation.

scholarly journals Centella asiatica (L.) Urb. Prevents Hypertension and Protects the Heart in Chronic Nitric Oxide Deficiency Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohd Khairulanwar Bunaim ◽  
Yusof Kamisah ◽  
Mohd Noor Mohd Mustazil ◽  
Japar Sidik Fadhlullah Zuhair ◽  
Abdul Hamid Juliana ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Rat Model ◽  
Antioxidant Properties ◽  
Centella Asiatica ◽  
Sprague Dawley ◽  
Cardiac Damage ◽  
Ace Activity

Background: Hypertension is a major risk factor for cardiovascular disease (CVD), which is the number one cause of global mortality. The potential use of natural products to alleviate high blood pressure has been demonstrated to exert a cardioprotective effect. Centella asiatica (L.) Urb. belongs to the plant family Apiaceae (Umbelliferae). It contains a high amount of triterpenoid and flavonoid that have antioxidant properties and are involved in the renin-angiotensin-aldosterone system which is an important hormonal system for blood pressure regulation.Objective: This study aimed to investigate the effects of C. asiatica ethanolic extract on blood pressure and heart in a hypertensive rat model, which was induced using oral N(G)-nitro-l-arginine methyl ester (l-NAME).Methods: Male Sprague-Dawley rats were divided into five groups and were given different treatments for 8 weeks. Group 1 only received deionized water. Groups 2, 4, and 5 were given l-NAME (40 mg/kg, orally). Groups 4 and 5 concurrently received C. asiatica extract (500 mg/kg, orally) and captopril (5 mg/kg, orally), respectively. Group 3 only received C. asiatica extract (500 mg/kg body weight, orally). Systolic blood pressure (SBP) was measured at weeks 0, 4, and 8, while serum nitric oxide (NO) was measured at weeks 0 and 8. At necropsy, cardiac and aortic malondialdehyde (MDA) contents, cardiac angiotensin-converting enzyme (ACE) activity, and serum level of brain natriuretic peptide (BNP) were measured.Results: After 8 weeks, the administrations of C. asiatica extract and captopril showed significant (p < 0.05) effects on preventing the elevation of SBP, reducing the serum nitric oxide level, as well as increasing the cardiac and aortic MDA content, cardiac ACE activity, and serum brain natriuretic peptide level.Conclusion:C. asiatica extract can prevent the development of hypertension and cardiac damage induced by l-NAME, and these effects were comparable to captopril.

Rapid cardiovascular effects of dexamethasone in rabbits with meconium-induced acute lung injury

2008 ◽  
Vol 86 (11) ◽  
pp. 804-814 ◽  
Author(s):  
Daniela Mokra ◽  
Ingrid Tonhajzerova ◽  
Juraj Mokry ◽  
Anna Drgova ◽  
Maria Petraskova ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Side Effects ◽  
Rabbit Model ◽  
Intratracheal Instillation ◽  
Cardiovascular Effects ◽  
Meconium Aspiration Syndrome ◽  
Cardiovascular Side Effects ◽  
Acute Side Effects ◽  
Systemic Glucocorticoids

Glucocorticoids may improve lung function in newborns with meconium aspiration syndrome (MAS), but information on the acute side effects of glucocorticoids in infants is limited. In this study using a rabbit model of MAS, we addressed the hypothesis that systemic administration of dexamethasone causes acute cardiovascular changes. Adult rabbits were treated with 2 intravenous doses of dexamethasone (0.5 mg/kg each) or saline at 0.5 h and 2.5 h after intratracheal instillation of human meconium or saline. Animals were oxygen-ventilated for 5 h after the first dose of treatment. Blood pressure, heart rate, and short-term heart rate variability (HRV) were analyzed during treatment, for 5 min immediately after each dose, and for the 5 h of the experiment. In the meconium-instilled animals, dexamethasone increased blood pressure, decreased heart rate, increased HRV parameters, and caused cardiac arrhythmia during and immediately after administration. In the saline-instilled animals, the effect of dexamethasone was inconsistent. In these animals, the acute effects of dexamethasone on blood pressure and cardiac rhythm were reversed after 30 min, whereas heart rate continued to decrease and HRV parameters continued to increase for 5 h after the first dose of dexamethasone. These effects were more pronounced in meconium-instilled animals. If systemic glucocorticoids are used in the treatment of MAS, cardiovascular side effects of glucocorticoids should be considered.

scholarly journals Fentanyl Pretreatment Modifies Anaesthetic Induction with Etomidate

1988 ◽  
Vol 16 (2) ◽  
pp. 171-176 ◽  
Author(s):  
R. J. Stockham ◽  
T. H. Stanley ◽  
N. L. Pace ◽  
S. Gillmor ◽  
F. Groen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Side Effects ◽  
Linear Regression ◽  
Anaesthetic Induction ◽  
Arterial Blood ◽  
Group I ◽  
Haemodynamic Changes ◽  
Induction Of Anaesthesia ◽  
Fentanyl Group

Haemodynamic changes and side-effects of induction of anaesthesia with etomidate were evaluated in 60 ASA Class I or II patients. The objective was to find an optimal pre-induction dose of fentanyl which eliminated haemodynamic changes and side-effects during induction and intubation without introducing other problems. Patients were randomly assigned to four groups according to the pretreatment dose of fentanyl (Group I= 2 ml normal saline; Group II= 100 μg of fentanyl; Group III= 250μg of fentanyl; Group IV = 500 μg of fentanyl) administered intravenously five minutes prior to induction of anaesthesia with etomidate, 0.3 mg/kg. There was an increasing incidence of apnoea (53, 87, 87 and 100% in Groups I-IV respectively) and a decreasing incidence of myoclonus (60, 33, 13 and 0% in Groups I-IV respectively) and injection pain (53, 13, 7 and 0% in Groups I-IV respectively), P< 0.002 chi-square test for linear trends, with increasing fentanyl dosage. The incidences of postoperative nausea and vomiting were similar in the four groups. There were also significant linear regression relationships (P< 0.01 ANOVA for linear regression) between increasing doses of fentanyl administered before etomidate and the prevention of increases in systolic blood pressure and heart rate during the induction-intubation sequence. The data demonstrate that increasing pre-induction doses of fentanyl are more effective at minimising side-effects and preventing increases in systolic arterial blood pressure and heart rate but also increase the incidence of apnoea during induction. The results suggest that 500 μg of fentanyl is an ideal pretreatment dose in fit patients prior to anaesthetic induction with etomidate.

Buprenorphine alleviation of pain does not compromise the rat monoarthritic pain model

2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson
Keyword(s):  
Rat Model ◽  
Joint Stiffness ◽  
Positive Control ◽  
Negative Control ◽  
Pain Tolerance ◽  
Control Group ◽  
Mechanical Stimuli ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
A Minor

Abstract Aims This study investigated the effects of buprenorphine treatment on pain and welfare parameters and model specific parameters in a rat model of monoarthritis to eliminate unnecessary pain from this model. Methods 32 male Sprague Dawley rats were divided into four groups: (1) A negative control without arthritis receiving no analgesia. (2) A positive monoarthritic control group receiving no analgesia, but subcutaneous saline injections twice a day. (3) A positive control with monoarthritis receiving subcutaneous carprofen once a day and saline once a day. (4) A group with monoarthritis receiving subcutaneous buprenorphine twice a day. Monoarthritis was induced with an injection of 0.02 ml Complete Freund’s Adjuvant intra-articularly in the left tibiotarsal joint. Treatment with analgesia was initiated at day 15 and the rats were euthanized at day 23. Results The induced monoarthritis elicited a pronounced acute inflammation. Several parameters such as bodyweight, mobility, stance, joint-stiffness and lameness scores were affected. A marked mechanical hyperalgesia in the tarsal area was observed by Electronic Von Frey testing, but no severe compromise of the animal welfare was seen at any time. Signs of chronic development began to appear from day 10 after the monoarthritic induction. No significant change in serum cytokines and faecal corticosterone measurements was found after administration of buprenorphine. A minor decrease in body weight was seen, and a higher pain tolerance to mechanical stimuli was observed, indicating pain alleviation. The histological examination confirmed monoarthritic development in all monoarthritic rats and revealed periarticular lesions suggesting diffusion of adjuvant from intra-articular injection site to the periphery. Conclusions The study demonstrated that buprenorphine has an analgesic effect in the adjuvant induced monoarthritic rat model, without obvious interference with the development of arthritis.

A STANDARDIZED METHOD FOR THE PRODUCTION OF HEMORRHAGIC SHOCK IN THE RAT

1955 ◽  
Vol 33 (3) ◽  
pp. 436-447 ◽  
Author(s):  
H. G. Downie ◽  
J. A. F. Stevenson
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mortality Rate ◽  
Hemorrhagic Shock ◽  
Respiratory Rate ◽  
Rectal Temperature ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Standardized Method

Although the blood pressure is one of the important criteria in the standardization of hemorrhagic shock in the dog, it has rarely been used for this purpose in the rat. A method resembling the reservoir technique developed by Wiggers and Werle (1942) for the dog using blood pressure as the criterion has been modified for use with the rat. Male Sprague-Dawley rats weighing approximately 400 gm. were used. In the standardization of this technique the blood pressure was reduced to 30 mm. Hg in a 10-min. period of hemorrhage and then maintained at this level by subsequent small hemorrhages into the reservoir until reinfusion indicated the beginning of vascular collapse, at which time all the blood in the reservoir was returned. Considering that those animals which lived longer than 48 hr. were survivors, in a series of 27 animals, 21 died and 6 survived—a mortality rate of 78%.During the hypotensive period there was a consistent and steady drop in the respiratory rate and rectal temperature. The heart rate declined initially and tended to recover as the hypotensive period progressed. After reinfusion the blood pressure rose but. did not reach prehemorrhage levels. Hemorrhage into the bowel and convulsions were significant postreinfusion findings.

scholarly journals Inhaling Hydrogen Ameliorates Early Postresuscitation EEG Characteristics in an Asphyxial Cardiac Arrest Rat Model

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Gang Chen ◽  
Jingru Li ◽  
Jianjie Wang ◽  
Bihua Chen ◽  
Yongqin Li
Keyword(s):  
Cardiac Arrest ◽  
Rat Model ◽  
Animal Studies ◽  
Onset Time ◽  
Quantitative Eeg ◽  
Permutation Entropy ◽  
Sprague Dawley ◽  
Ctrl Group ◽  
Neurological Outcomes ◽  
Prognostic Accuracy

Background. Electroencephalography (EEG) is commonly used to assess the neurological prognosis of comatose patients after cardiac arrest (CA). However, the early prognostic accuracy of EEG may be affected by postresuscitation interventions. Recent animal studies found that hydrogen inhalation after CA greatly improved neurological outcomes by selectively neutralizing highly reactive oxidants, but the effect of hydrogen inhalation on EEG recovery and its prognostication value are still unclear. The present study investigated the effects of hydrogen inhalation on early postresuscitation EEG characteristics in an asphyxial CA rat model. Methods. Cardiopulmonary resuscitation was initiated after 5 min of untreated CA in 40 adult female Sprague-Dawley rats. Animals were randomized for ventilation with 98% oxygen plus 2% hydrogen (H2) or 98% oxygen plus 2% nitrogen (Ctrl) under normothermia for 1 h. EEG characteristics were continuously recorded for 4 h, and the relationships between quantitative EEG characteristics and 96 h neurological outcomes were investigated. Results. No differences in baseline and resuscitation data were observed between groups, but the survival rate was significantly higher in the H2 group than in the Ctrl group (90% vs. 40%, P<0.01). Compared to the Ctrl group, the H2 group showed a shorter burst onset time (21.85 [20.00–23.38] vs. 25.70 [22.48–30.05], P<0.01) and time to normal trace (169.83 [161.63–208.55] vs. 208.39 [186.29–248.80], P<0.01). Additionally, the burst suppression ratio (0.66 ± 0.09 vs. 0.52 ± 0.17, P<0.01) and weighted‐permutation entropy (0.47 ± 0.16 vs. 0.34 ± 0.13, P<0.01) were markedly higher in the H2 group. The areas under the receiver operating characteristic curves for the 4 EEG characteristics in predicting survival were 0.82, 0.84, 0.88, and 0.83, respectively. Conclusions. In this asphyxial CA rat model, the improved postresuscitation EEG characteristics for animals treated with hydrogen are correlated with the better 96 h neurological outcome and predicted survival.

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