scholarly journals Use of Flavored Tablets of Gabapentin and Carprofen to Attenuate Postoperative Hypersensitivity in an Incisional Pain Model in Rats (Rattus norvegicus)

Author(s):  
Brian P Zude ◽  
Katechan Jampachaisri ◽  
Cholawat Pacharinsak

Providing postoperative analgesia to rats by oral administration, compared with injections, reduces stress from frequent handling and is technically easier for investigators. The purpose of this study was to investigate whether bacon-flavored tablets containing gabapentin, carprofen or a combination of both drugs effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Forty-eight Sprague–Dawley rats were randomly assigned to 1 of 5 treatment groups: placebo tablet; a single, subcutaneous injection of buprenorphine sustained release at 1.2 mg/kg; gabapentin 90 mg/tablet; carprofen 5 mg/tablet; gabapentin 90 mg and carprofen 5 mg/tablet (gabapentin/carprofen). Tablets were given to rats on days -3, -2, -1, 0 (surgery), 1, and 2. Rats were anesthetized using isoflurane. A 1 cm skin incision was made aseptically on the plantar surface of the left hindpaw and closed by using suture. Mechanical (von Frey monofilament) and thermal (Hargreaves method) hypersensitivity were tested daily, and analyzed on days -1, 1, 2, and 3. The amount of tablet consumed was recorded daily; postoperatively rats consumed 101 to 133 mg/kg of gabapentin, 5.5 to 5.8 mg/kg of carprofen, and 86-137/1.9-3 mg/kg of gabapentin/carprofen, respectively. Both the gabapentin and carprofen groups displayed attenuated mechanical hypersensitivity on all 3 postsurgical days and decreased thermal hypersensitivity on Day 3. The gabapentin/ carprofen group showed attenuated mechanical hypersensitivity on Day 2 and 3, but no significant reduction of thermal hypersensitivity. These data suggest that both gabapentin and carprofen, given orally by flavored tablet, effectively attenuate postoperative mechanical hypersensitivity for 3 d after surgery in a rat model of incisional pain.

Author(s):  
Eden D Alamaw ◽  
Benjamin D Franco ◽  
Katechan Jampachaisri ◽  
Monika K Huss ◽  
Cholawat Pacharinsak

A new extended-release buprenorphine (XR), an FDA-indexed analgesic, has recently become available to the laboratoryanimal community. However, the effectiveness and dosing of XR has not been extensively evaluated for rats. We investigatedXR’s effectiveness in attenuating postoperative hypersensitivity in a rat incisional pain model. We hypothesized that highdose of XR would attenuate mechanical and thermal hypersensitivity more effectively than the low dose of XR in this model. We performed 2 experiments. In experiment 1, male adult Sprague–Dawley rats (n = 31) were randomly assigned to 1 of the 4 treatment groups: 1) saline (saline, 0.9% NaCl, 5 mL/kg, SC, once); 2) sustained-release buprenorphine (Bup-SR; 1.2 mg/kg, SC, once), 3) low-dose extended-release buprenorphine (XR-Lo; 0.65 mg/kg, SC, once), and 4) high-dose extended-releasebuprenorphine (XR-Hi; 1.3 mg/kg, SC, once). After drug administration, a 1 cm skin incision was made on the plantar hind paw under anesthesia. Mechanical and thermal hypersensitivity were evaluated 1 d before surgery (D-1), 4 h after surgery (D0), and for 3 d after surgery (D1, D2, and D3). In experiment 2, plasma buprenorphine concentration (n = 39) was measured at D0, D1, D2, and D3. Clinical observations were recorded daily, and a gross necropsy was performed on D3. Mechanical and thermal hypersensitivity were measured for 3 d (D0-D3) in the saline group. Bup-SR, XR-Lo, and XR-Hi effectively attenuated mechanical hypersensitivity for D0-D3. Plasma buprenorphine concentrations remained above 1 ng/mL on D0 and D1 in all treatment groups. No abnormal clinical signs were noted, but injection site reactions were evident in the Bup-SR (71%), XR-Lo (75%), and XR-Hi (87%) groups. This study indicates that XR-Hi did not attenuate hypersensitivity more effectivelythan did XR-Lo in this model. XR 0.65 mg/kg is recommended to attenuate postoperative mechanical hypersensitivity for upto 72 h in rats in an incisional pain model.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246213
Author(s):  
Alexandra Blaney ◽  
Katechan Jampachaisri ◽  
Monika K. Huss ◽  
Cholawat Pacharinsak

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Na Cui ◽  
Hao Wang ◽  
Yun Long ◽  
Longxiang Su ◽  
Dawei Liu

The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2p<0.001and MMP-9p<0.001were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1p<0.001and syndecan-1p=0.011protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treatedp=0.03. In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.


2018 ◽  
Vol 52 (6) ◽  
Author(s):  
Maria Concepcion C. Sison ◽  
Lynn Crisanta R. Panganiban ◽  
Daisy Mae A. Bagaoisan ◽  
Nelia P. Cortes-Maramba

Objective. To To evaluate potential effects of the aqueous extract of Quassia amara L. leaves on the cardiovascular and respiratory systems of adult male Sprague- Dawley rats. Methods. The cardiovascular and respiratory effects of the Quassia amara L. leaf extract on adult male SpragueDawley rats were assessed using non-invasive blood pressure (NIBP) determination and head-out plethysmography, respectively, in a randomized, parallel group study. Mean observations of blood pressure and heart rate were recorded at different time periods after dosing. Respiratory flow and irritation effects were evaluated using mean observations of respiratory rate (RR), tidal volume (TV), mid-expiratory flow rate (EF50), time of inspiration (TI) and expiration (TE), and time of break (TB) and pause (TP). Results. There were no significant differences among the control and the treatment groups in SBP, DBP and HR parameters. The extract showed statistically significant effect on mean RR by time period (F=2.45, p=0.0234), trends over time of TV among the dose groups (F=2.00, p=0.0202), and EF50 among dose groups ((F=3.11, p=0.0422). However, these did not correlate with the changes in the time of break (TB) and time of pause (TP) which are more sensitive and specific tests for respiratory irritation. Conclusion. Aqueous leaf extract of Quassia appeared to have no significant effects on SBP, DPB, Pulse pressure, and HR. There are no conclusive dose-related respiratory flow or pulmonary irritation effects.


1985 ◽  
Vol 248 (1) ◽  
pp. E70-E74 ◽  
Author(s):  
R. A. Bennett ◽  
P. C. Colony ◽  
J. L. Addison ◽  
D. E. Rannels

The effects of adrenalectomy, with and without subsequent glucocorticoid replacement therapy, on postpneumonectomy compensatory lung growth in the rat were investigated. Male Sprague-Dawley rats (200-230 g) were subjected to no operation (UNOP), left pneumonectomy (PNX), or PNX preceded by bilateral adrenalectomy 5 days earlier (ADX/PNX). At 14 days post-PNX, when compensatory lung growth is normally complete in 200-g rats, right lung (RL) dry weights of PNX (263 +/- 6 mg, n = 26) and ADX/PNX (334 +/- 13 mg, n = 25) rats were increased 58 and 101%, respectively, relative to UNOP controls (166 +/- 5 mg, n = 10). Increases in total DNA, RNA, and protein in the right lungs of PNX and ADX/PNX rats occurred in proportion to RL dry mass. The increase in all parameters examined in PNX and ADX/PNX rats at 7 days post-PNX was half that at 14 days, indicating linear lung growth in both treatment groups. The stimulatory effect of ADX on lung growth was blocked by hydrocortisone acetate (HCA), administered intraperitoneally in daily doses of 5 mg/kg, beginning on the day of PNX. The RL dry weights of HCA-treated ADX/PNX rats (241 +/- 7 mg, n = 10) did not differ significantly from the corresponding value in PNX rats (270 +/- 14 mg, n = 7). The lower RL weights in the HCA-treated rats resulted from an inhibition of cell division, as evidenced by the total RL DNA content, which was similar to that in PNX animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 950 ◽  
Author(s):  
Katrina Frost ◽  
Maaria Shah ◽  
Vivian S.Y. Leung ◽  
Daniel S.J. Pang

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an aversion-avoidance paradigm, 24 rats were exposed to isoflurane or desflurane (n = 12 per group) at initial exposure. Fourteen rats were then re-exposed to isoflurane or desflurane (n = 7 per group), after a 7 days washout period. Initial exposure: time to recumbency was faster for desflurane than isoflurane (p = 0.0008, 95% CI [-12.9 to 32.6 s]), with 9/12 and 6/12 rats becoming recumbent, respectively. At initial exposure, there was no difference between groups in time to withdrawal (p = 0.714). At re-exposure, all rats withdrew and no rats became recumbent. Time to withdrawal at re-exposure did not differ between treatment groups (p = 0.083). Compared to initial exposure, time to withdrawal during re-exposure was similar for isoflurane (p = 0.228) and faster with desflurane (p = 0.012, 95% CI [19.1 to 49.5 s]). Isoflurane and desflurane are similarly aversive, with aversion increasing at re-exposure. The shorter time from exposure to recumbency with desflurane indicates that any distress is of a shorter duration when compared with isoflurane.


2017 ◽  
Vol 16 (1) ◽  
pp. 167-167
Author(s):  
M.S. Berke ◽  
Klas S.P. Abelson

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.


Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3795
Author(s):  
Jihye Bang ◽  
Won Kyung Jeon

Mumefural (MF), a bioactive component of the processed fruit of Prunus mume Sieb. et Zucc, is known to inhibit platelet aggregation induced by agonists in vitro. In this study, we investigated the anti-thrombotic effects of MF using a rat model of FeCl3-induced arterial thrombosis. Sprague–Dawley rats were intraperitoneally injected with MF (0.1, 1, or 10 mg/kg) 30 min before 35% FeCl3 treatment to measure the time to occlusion using a laser Doppler flowmeter and to assess the weight of the blood vessels containing thrombus. MF treatment significantly improved blood flow by inhibiting occlusion and thrombus formation. MF also prevented collagen fiber damage in injured vessels and inhibited the expression of the platelet activation-related proteins P-selectin and E-selectin. Moreover, MF significantly reduced the increased inflammatory signal of nuclear factor (NF)-κB, toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in blood vessels. After administration, MF was detected in the plasma samples of rats with a bioavailability of 36.95%. Therefore, we suggest that MF may improve blood flow as a candidate component in dietary supplements for improving blood flow and preventing blood circulation disorders.


2019 ◽  
Vol 172 (1) ◽  
pp. 132-145 ◽  
Author(s):  
Silvia Cirillo ◽  
Fabio Vivarelli ◽  
Eleonora Turrini ◽  
Carmela Fimognari ◽  
Sabrina Burattini ◽  
...  

Abstract Despite the knowledge gap regarding the risk-benefit ratio of the electronic cigarette (e-cig), its use has grown exponentially, even in teenagers. E-cig vapor contains carcinogenic compounds (eg, formaldehyde, acetaldehyde, and acrolein) and free radicals, especially reactive oxygen species (ROS) that cause toxicological effects, including DNA damage. The role of e-cig voltage customization on molecule generation has been reported, but the effects of the resistance on e-cig emissions and toxicity are unknown. Here, we show that the manipulation of e-cig resistance influences the carbonyls production from nonnicotine vapor and the oxidative and inflammatory status in a rat model. Fixing the voltage at the conventional 3.5 V, we observed that the amount of the selected aldehydes increased as the resistance decreased from 1.5 to 0.25 Ω. Under these conditions, we exposed Sprague Dawley rats to e-cig aerosol for 28 days, and we studied the pulmonary inflammation, oxidative stress, tissue damage, and blood homeostasis. We found a perturbation of the antioxidant and phase II enzymes, probably related to the increased ROS levels due to the enhanced xanthine oxidase and P450-linked monooxygenases. Furthermore, frames from scanning electron microscope showed a disorganization of alveolar and bronchial epithelium in 0.25 Ω group. Overall, various toxicological outcomes, widely recognized as smoke-related injuries, can potentially occur in e-cig consumers who use low-voltage and resistance device. Our study suggests that certain “tips for vaping safety” cannot be established, and encourages further independent investigations to help public health agencies in regulating the e-cig use.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hoon Jang ◽  
Woong-Jin Bae ◽  
Seung-Mo Yuk ◽  
Dong-Seok Han ◽  
U-Syn Ha ◽  
...  

Seoritae is a type of black soybean that is known to have health-promoting effects due to its high isoflavone and anthocyanin contents. We evaluated whether Seoritae extract (SE) had beneficial effects on the reduction of prostate weight in a rat model of benign prostatic hyperplasia (BPH). BPH was induced by intramuscular injections of testosterone enanthate once a week for 5 weeks in Sprague-Dawley rats, and rats were treated with or without daily oral doses of SE during BPH induction. After 5 weeks, the oxidative stress (superoxide dismutase and 8-hydroxy-2-deoxyguanosine), apoptosis (caspase-3), and activity of 5-alpha reductase were evaluated in the serum and prostate. The SE treatment group showed a significant decrease in prostate weight, oxidative stress, apoptosis, and 5-alpha reductase activity compared to the nontreated BPH group. These results show that SE is effective in decreasing the weight and proliferation of the prostate, and suggest that SE may be an effective treatment for BPH.


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