Evaluation of dosages and routes of administration of tramadol analgesia in rats using hot-plate and tail-flick tests

Tramadol is an opioid-like analgesic with relatively mild side effects. Because it is inexpensive and is not classified as a controlled substance by the US federal government, the authors wanted to evaluate its applicability as a practical and effective analgesic in male Sprague Dawley rats. They measured the efficacy of four dosages (4, 12.5, 25 or 50 mg tramadol per kg body weight) and three routes of administration (per os (p.o.) in a flavored gelatin cube, subcutaneous (s.c.) or intraperitoneal (i.p.)) using the hot-plate test and the tail-flick test, which were carried out 1 week apart. Rats that were dosed p.o. were given flavored gelatin cubes without tramadol on the 2 d before testing to help them become acclimated to the gelatin, in an effort to increase the likelihood that they would consume the gelatin on the testing day. Results from the hot-plate and tail-flick tests for rats that were given tramadol p.o. were similar before and after administration, regardless of tramadol dosage, suggesting that this route of administration was not effective. The s.c. route of administration was effective at dosages of 25 mg and 50 mg tramadol per kg body weight, although these dosages also resulted in sedation and skin lesions. The i.p. route of administration was also effective at dosages of 12.5 mg, 25 mg and 50 mg tramadol per kg body weight, though sedation was observed at dosages of 25 mg and 50 mg per kg body weight. Intraperitoneal administration of 12.5 mg tramadol per kg body weight had no notable side effects, and the authors plan to further study this dosage and route of administration in a rodent surgical model of pain.     

Rat Experimental Model of Myocardial Ischemia/Reperfusion Injury: An Ethical Approach to Set up the Analgesic Management of Acute Post-Surgical Pain

Rationale

During the past 30 years, myocardial ischemia/reperfusion injury in rodents became one of the most commonly used model in cardiovascular research. Appropriate pain-prevention appears critical since it may influence the outcome and the results obtained with this model. However, there are no proper guidelines for pain management in rats undergoing thoracic surgery. Accordingly, we evaluated three analgesic regimens in cardiac ischemia/reperfusion injury. This study was strongly focused on 3R’s ethic principles, in particular the principle of Reduction.

Methods

Rats undergoing surgery were treated with pre-surgical tramadol (45 mg/kg intra-peritoneal), or carprofen (5 mg/kg sub-cutaneous), or with pre-surgical administration of carprofen followed by 2 post-surgery tramadol injections (multi-modal group). We assessed behavioral signs of pain and made a subjective evaluation of stress and suffering one and two hours after surgery.

Results

Multi-modal treatment significantly reduced the number of signs of pain compared to carprofen alone at both the first hour (61±42 vs 123±47; p<0.05) and the second hour (43±21 vs 74±24; p<0.05) post-surgery. Tramadol alone appeared as effective as multi-modal treatment during the first hour, but signs of pain significantly increased one hour later (from 66±72 to 151±86, p<0.05). Carprofen alone was more effective at the second hour post-surgery when signs of pain reduced to 74±24 from 113±40 in the first hour (p<0.05). Stress behaviors during the second hour were observed in only 20% of rats in the multimodal group compared to 75% and 86% in the carprofen and tramadol groups, respectively (p<0.05).

Conclusions

Multi-modal treatment with carprofen and tramadol was more effective in preventing pain during the second hour after surgery compared with both tramadol or carprofen. Our results suggest that the combination of carprofen and tramadol represent the best therapy to prevent animal pain after myocardial ischemia/reperfusion. We obtained our results accordingly with the ethical principle of Reduction.     

曲马朵与二氢埃托啡协同镇痛并推迟大鼠急性耐受

本文旨在研究曲马朵（tramadol,TRA）和二氢埃托啡（dihydroetorphine,DHE）联合用药是否可产生协同镇痛并延缓耐受的发生。TRA（mg,腹腔注射）与DHE（ng,皮下注射）按固定比率给药（1：6．25,1：12．5,1：25,1：50,l：100,1：200）,用热辐射甩尾法评价镇痛效应,采用等高线法评估药物的协同作用。在急性耐受实验中,连续6次注射TRA（20mg／kg）、DHE（1000ng／kg）或两药的组合（TRA20mg／kg＋DHE250ng／kg）。结果显示：（1）除1mg：6．25ng和1mg：50ng两个比例外,其他所有比例用药均产生显著的协同镇痛效应;（2）TRA与DHE联合用药的疗效在连续给药中持续时间明显延长,提示二者联合使用可延缓耐受。以上结果提示：TRA与DHE在一定剂量比范围内可产生协同镇痛效应,并可推迟耐受的形成。     

Evaluation of a combination of tiletamine and zolazepam as an anesthetic for laboratory rodents

A combination of equal parts of tiletamine hydrochloride and zolazepam hydrochloride was evaluated as an injectable anesthetic for rats, mice, and hamsters. The drug produced satisfactory anesthesia and analgesia in rats when given either intraperitoneally or intramuscularly at concentrations of 20 or 40 mg/kg body weight. The length of anesthesia was dose dependent and was somewhat longer in females as compared to males, and inbreds compared to outbreds. Incisions through the peritoneum of anesthetized rats evoked little or no response, whereas cervical skin incisions evoked a slight response in many rats. Anesthesia without analgesia occurred in mice at dosages of 80 mg/kg body weight and higher, however, many animals developed respiratory distress and died at dosages of 100 to 160 mg/kg body weight. In hamsters, anesthesia but not analgesia occurred at drug concentrations of 50 to 80 mg/kg body weight. It was concluded that a tiletamine and zolazepam combination was an effective anesthetic for rats, but not for mice or hamsters.     

Relationship between the antitussic and analgesic activity of substances

The authors studied relationship between the antitussic and analgesic activity of substances. The antitussic effect of codeine, tilidine, tramadol and pentazocine has been studied in nonanesthetized healthy cats. The drugs except tilidine, were administered intraperitoneally in a dose of 10 mg/kg body weight. Tilidine was administered intramuscularly in the same dose. Cough induced in nonanesthetized cats by mechanical irritation of laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. A significant decrease of the subsequent cough parameters was observed after the application of codeine, tilidine, tramadol and pentazocine. Naloxone given 5 min before the application of the drug has not prevented the cough-suppressing effect due to codeine. Naloxone alone administered in a dose of 1 mg/kg body weight has not significantly influenced the experimentally-induced cough reflex in nonanesthetized cats.     

Immobilization of black bears (Ursus americanus) with a combination of butorphanol, azaperone, and medetomidine

Sixteen captive and five free-ranging black bears (Ursus americanus) were immobilized with a combination of butorphanol, azaperone, and medetomidine (BAM). The BAM drug combination was premixed using 0.5 ml butorphanol (30 mg/ml), 0.25 ml azaperone (50 mg/ml), and 0.25 ml medetomidine (20 mg/ml) per milliliter to yield a final mix of (15 mg butorphanol+12.5 mg azaperone+5 mg medetomidine)/ml. This combination, dosed at 0.4 ml BAM/approximately 23 kg estimated body weight, provided a mean induction time of 10 min (95% confidence interval [CI]=2 min), consistent anesthesia without apparent adverse effects, and smooth recovery (mean=15 min, 95% CI=4 min) after antagonism with atipamezole (5 mg/mg medetomidine) alone or in combination with naltrexone (5 mg/mg butorphanol). Based on our initial observations, BAM appears to be a reversible and accessible drug combination for immobilizing black bears that merits further evaluation for field use.     

Expression stability of commonly used reference genes in canine articular connective tissues

Background

Pain of mild to moderate grade is difficult to detect in laboratory mice because mice are prey animals that attempt to elude predators or man by hiding signs of weakness, injury or pain. In this study, we investigated the use of telemetry to identify indicators of mild-to-moderate post-laparotomy pain.

Results

Adult mice were subjected to laparotomy, either combined with pain treatment (carprofen or flunixin, 5 mg/kg s/c bid, for 1 day) or without pain relief. Controls received anesthesia and analgesics or vehicle only. Telemetrically measured locomotor activity was undisturbed in all animals, thus confirming that any pain experienced was of the intended mild level. No symptoms of pain were registered in any of the groups by scoring the animals' outer appearance or spontaneous and provoked behavior. In contrast, the group receiving no analgesic treatment after laparotomy demonstrated significant changes in telemetry electrocardiogram recordings: increased heart rate and decreased heart rate variability parameters pointed to sympathetic activation and pain lasting for 24 hours. In addition, core body temperature was elevated. Body weight and food intake were reduced for 3 and 2 days, respectively. Moreover, unstructured cage territory and destroyed nests appeared for 1–2 days in an increased number of animals in this group only. In controls these parameters were not affected.

Conclusion

In conclusion, real-time telemetric recordings of heart rate and heart rate variability were indicative of mild-to-moderate post-laparotomy pain and could define its duration in our mouse model. This level of pain cannot easily be detected by direct observation.     

Use of oral buprenorphine ('buprenorphine jello') for postoperative analgesia in rats--a clinical trial

Buprenorphine (0.1, 0.2, 0.3 or 0.4 mg/kg) in a flavoured gelatin base was administered preoperatively to rats undergoing a flank laparotomy. A control group of animals underwent surgery and received only flavoured gelatin. Body weight loss was significantly greater in the group which received no analgesia than in any of the analgesic-treated groups (P < 0.01). Food consumption was reduced significantly in all groups except in those animals which received 0.3 mg/kg buprenorphine. Water consumption was significantly reduced in the control (no analgesia) group (P < 0.001), but was not significantly depressed in the analgesic-treated groups (P > 0.05). Between-group comparisons did not show any significant difference between the different dose rates of analgesia used on either the change in body weight or the reduction in food or water consumption. The results of this study support the use of buprenorphine jelly for post-surgical analgesia in rats. This route of delivery is easy to use, and causes a minimum of stress to the rats.     

Duration of effects on clinical parameters and referred hyperalgesia in rats after abdominal surgery and multiple doses of analgesic

This study evaluated the duration of clinical effects and referred hyperalgesia in rats (n = 10 per group) undergo ing abdominal surgery with analgesics (ketoprofen at 3 mg/kg and buprenorphine at 0.01 or 0.1 mg/kg) administered intramuscularly twice daily for 72 h beginning prior to surgery; no-surgery and no-analgesia control groups were included. Food and water consumption and body weight were monitored daily. As a measure of referred hyperalgesia, tail-flick latency was measured daily, before and 4 h after analgesia administration. Compared with those of the no-surgery controls, significant decreases in food consumption and body weight occurred 24 h after surgery without analgesics. There were nonsignificant reductions in these effects by analgesics, but the benefits were not significantly different than those of saline. These parameters continued to be decreased with variable significance in the buprenorphine groups at 48 and 72 h after surgery. In both buprenorphine-treated groups, water consumption was significantly increased at 24 h after surgery but not at 48 or 72 h. Tail-flick latency was not significantly different between the no-surgery and no-analgesia groups but was significantly increased 4 h after high-dose buprenorphine administration and declined nonsignificantly over time in the other groups. We conclude that painful effects from surgery are present primarily during the first 24 h after surgery. The analgesic regimens tested did not completely reduce these effects. Buprenorphine was associated with adverse effects for as long as 72 h after surgery. Referred hyperalgesia from this abdominal surgery could not be measured using the tail-flick assay.     

Oral buprenorphine and aspirin analgesia in rats undergoing liver transplantation

The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg/kg/dose) or aspirin (100 mg/kg/dose) in raspberry-flavoured gelatine were compared to controls receiving no treatment or plain gelatine. The drugs were presented five times: immediately on recovery from anaesthesia and at 12 h intervals thereafter. All rats underwent right nephrectomy and replacement of their liver by an arterialized liver isograft preserved optimally for 24 h. All groups had reversible hepatic damage, lost weight and demonstrated severely reduced dark cycle activity after surgery. Neither treatment appeared to ameliorate the loss of body weight that probably reflected hepatic insufficiency during the first week as well as pain and surgical stress. In the second week, when liver function was 'normal', rats began to regain weight at the pre-transplant rate. Aspirin treatment significantly increased activity during the first and second dark cycles after surgery, whereas buprenorphine significantly increased activity during the second dark cycle only. Neither drug had any apparent adverse effects on the rats or on graft function. Postoperative oral administration of aspirin should be incorporated into future programmes of liver transplantation in rodents. More effective treatment in the immediate postoperative period may require oral administration of analgesia prior to surgery or a single subcutaneous injection of an analgesic agent on completion of surgery in addition to postoperative oral administration of aspirin.     

Analgesia induced by combined action of Tramadol and microwave irradiation in somatic pain in mice

In experiments on albino male mice weighing 24 to 32 g, we studied the suppression of the pain reaction induced by injection of formalin into the dorsal surface of the foot, using a combination of injection of tramadol hydrochloride (Tramal) in a dose of 0.42 mg/kg and irradiation of the acupuncture point (AP) E-36 with low-intensity microwaves (frequency 30 to 300 GHz and power rate density 3·10⁻⁹ W/cm²). The combined use of tramadol injection and the action of microwaves on the AP led to a decrease in the duration of the pain reaction (licking of the pain nidus), on average, by 58.2%, as compared with that in the control animal group. The analgesic effect was more strong in the case of such a combination than after isolated injection of tramadol in doses of 0.83 and 0.42 mg/kg (by 14.4 and by 10.0%, respectively) and isolated microwave irradiation of the AP TA E-36 (by 48.7%). The data obtained demonstrate the possibility of effective analgesia using a combination of microwave irradiation of the AP and the pharmacological influence with a significant decrease in the dose of the analgesic. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 314–319, July–August, 2006.     

Effect of Acetaminophen Alone and in Combination with Morphine and Tramadol on the Minimum Alveolar Concentration of Isoflurane in Rats

Background

It has been observed that acetaminophen potentiates the analgesic effect of morphine and tramadol in postoperative pain management. Its capacity as an analgesic drug or in combinations thereof to reduce the minimum alveolar concentration (MAC) of inhalational anesthetics represents an objective measure of this effect during general anesthesia. In this study, the effect of acetaminophen with and without morphine or tramadol was evaluated on the isoflurane MAC.

Methods

Forty-eight male Wistar rats were anesthetized with isoflurane in oxygen. MAC_ISO was determined from alveolar gas samples at the time of tail clamping without the drug, after administering acetaminophen (300 mg/kg), morphine (3 mg/kg), tramadol (10 mg/kg), acetaminophen (300 mg/kg) + morphine (3 mg/kg), and acetaminophen (300 mg/kg) + tramadol (10 mg/kg).

Results

The control and acetaminophen groups did not present statistically significant differences (p = 0.98). The values determined for MAC_ISO after treatment with acetaminophen + morphine, acetaminophen + tramadol, morphine, and tramadol were 0.98% ± 0.04%, 0.99% ± 0.009%, 0.97% ± 0.02%, and 0.99% ± 0.01%, respectively.

Conclusions

The administration of acetaminophen did not reduce the MAC of isoflurane and did not potentiate the reduction in MAC_ISO by morphine and tramadol in rats, and therefore does not present a sparing effect of morphine or tramadol in rats anesthetized with isoflurane.     

Effects of systemically administered monoamine reuptake blocking agents on patterns of buspirone-induced analgesia in rats

We have recently shown the serotonin 5-HT1A receptor agonist buspirone to produce analgesia in several pain tests in rats. As a 5-HT1A agonist, buspirone may change serotonergic (5-HT) tone to alter the balance of central monoaminergic (MA) systems that function in analgesia. MA-reuptake blocking drugs have been shown to produce analgesia, both when given alone and in combination with a variety of other agents, presumably via their action upon MA neurochemistry. The present study was undertaken to examine the effect of systemic administration of the 5-HT-reuptake blocker amitriptyline (AMI: 10 mg/kg), NE-reuptake blocker desipramine (DMI: 10 mg/kg) or DA-reuptake blocker GBR-12909 (7.5 mg/kg) on patterns of analgesia produced by buspirone (1-5 mg/kg) in thermal and mechanical pain tests in rats. Neither reuptake blocking agents or buspirone, when administered alone or in combination, produced overt changes in motor activity at the doses tested. AMI alone was not analgesic in either thermal or mechanical pain tests. In both assays, AMI reduced the analgesic action of buspirone, with greater effects seen in the thermal test. When administered alone, DMI produced significant analgesia against thermal and mechanical pain. DMI significantly attenuated the analgesic action of all doses of buspirone in both pain tests. Alone, GBR-12909 did not affect nociception in thermal or mechanical tests. GBR-12909 decreased buspirone-induced analgesia at all doses in the thermal test, while having no effect on buspirone-induced analgesia against mechanical pain. These results demonstrate that facilitation of 5-HT, NE and DA function with reuptake blocking drugs did not enhance the analgesic action of buspirone. These data indicate against the adjuvant use of reuptake blocking compounds and buspirone as analgesics. Furthermore, such findings may suggest other possible non-MA substrates of buspirone-induced analgesia.     

Analysis of interaction between etoricoxib and tramadol against mechanical hyperalgesia of spinal cord injury in rats

Drug combinations have the potential advantage of greater analgesia over monotherapy. The present study was aimed to assess any possible interaction (additive or potentiation) in the antinociceptive effects of etoricoxib; a novel cyclooxygenase-2 inhibitor, and tramadol; a typical opioid agonist when administered in combination against mechanical hyperalgesia induced by spinal cord injury in rats. The nature of interaction was analyzed using surface of synergistic interaction (SSI) analysis and an isobolographic analysis. Etoricoxib or tramadol when administered alone to rats, exhibited different antihyperalgesic potencies (ED50 etoricoxib: 0.58+/-0.19 mg/kg, po; ED50 tramadol: 9.85+/-0.57 mg/kg, po). However, both the drugs were found to be long acting against this model of hyperalgesia. Further, etoricoxib and tramadol were co-administered in fixed ratios of ED50 fractions. One combination (0.29/4.79 mg/kg, po: etoricoxib/tramadol) exhibited additivity and other three combinations (0.15/2.39, 0.08/1.19, and 0.04/0.59 mg/kg, po: etoricoxib/tramadol) resulted in potentiation when analyzed by SSI. The SSI was calculated from the total antihyperalgesic effect produced by the combination after the subtraction of the antihyperalgesic effect produced by each of the individual drug. In the isobolographic analysis, the experimental ED50 was found to be far below the line of additivity also indicating a significant (P < 0.05) synergistic antihyperalgesic effect when etoricoxib and tramadol was co-administered to rats. The synergistic antihyperalgesic effect of etoricoxib and tramadol combination suggests that these combinations may have clinical utility in mechanical hyperalgesia associated with spinal injury.     

Thiorphan potentiation of stress-induced analgesia in the mouse

Experiments were done to examine the analgesic effect of thiorphan alone or in combination with stress in mice. Analgesia was assessed by measuring jump latencies from a 55 degrees C hot plate. Thiorphan exhibited weak analgesic properties evidenced by significant increases in jump latencies only after 300 mg/kg i.p. Additional experiments were done to see the effect of i.c.v. administration of thiorphan in the mouse hot plate test. Control experiments revealed that either i.c.v. saline or sham caused naloxone reversible analgesia which was potentiated by thiorphan (100 mg/kg i.p.). Immobilization stress-induced analgesia was also potentiated by thiorphan (100 mg/kg i.p.) and antagonized by naloxone (10 mg/kg i.p.). The results suggest that stress-induced analgesia in the mouse is associated with an endogenous opioid mechanism which is potentiated when enkephalin degradation is inhibited by thiorphan.     

Influence of buprenorphine analgesia on post-operative recovery in two strains of rats.

The objective of this study was to establish an effective post-operative analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats. Buprenorphine (0.01 or 0.05 mg/kg), a partial mu opioid agonist, was administered subcutaneously immediately on completion of a standardized surgical procedure, involving anaesthesia, laparotomy and visceral manipulation. Two of the four treatment groups and the saline control group received a second injection 9 h later. Behavioural observations by three independent observers provided no information in assessing pain in this model. All rats lost weight, consumed less food and water after surgery. On the first day, both SD and DA rats receiving buprenorphine lost less weight than untreated control groups. Using weight loss as an efficacy criterion, low-dose buprenorphine, given once or twice, provided effective analgesia in SD rats. A higher single dose provided no additional benefit and a second dose was detrimental, reducing body weight and food intake. In DA rats, the high dose, given twice, appeared to be more effective than the lower dose. All DA cage cohorts consumed < 10% pre-operative food despite buprenorphine treatment, suggesting a higher dosage may be necessary. However, all SD and 80% DA rats who received no buprenorphine gained body weight on the second day, whereas most of the buprenorphine-treated rats continued to lose weight for another 2 days, despite increased food consumption by both strains. Buprenorphine may adversely affect intestinal function over a number of days due to its enterohepatic circulation; this effect may be more severe in DA rats. Adverse metabolic effects of buprenorphine and other opioids may preclude their use in the future if it can be shown that non-steroidal anti-inflammatory drugs (NSAIDs) provide equally effective analgesia.     

Liposome-encapsulated oxymorphone hydrochloride provides prolonged relief of postsurgical visceral pain in rats

Adequate pain control is necessary for optimal postsurgical recovery and humane treatment of laboratory and companion animals. Opioid drugs are currently the most potent analgesic agents available in human and veterinary medicine. Long-acting formulations of opioid drugs confer several important advantages over standard pharmaceutical preparations, especially for use in animals. A long-acting formulation of oxymorphone hydrochloride was produced by encapsulation into liposomes. Liposome-encapsulated (LE) oxymorphone was tested in a rat model of visceral postoperative pain. Rats were given one subcutaneous injection of LE oxymorphone (1.2 or 1.6 mg/kg of body weight) or standard oxymorphone (0.3 mg/kg) at the time of intestinal transection or resection. A single administration of LE oxymorphone hydrochloride was as effective for relief of postoperative pain in rats (P = 0.18), as were multiple (q4 h or q8 h) injections of 0.3 mg/kg of the standard pharmaceutical preparation. The rats given LE oxymorphone prior to intestinal resection also had significantly higher body weight at three and seven days after surgery than did rats that were given standard oxymorphone. In conclusion, LE oxymorphone was effective in treating visceral pain associated with intestinal surgery in rats. On the basis of body weight gain, rats treated with LE oxymorphone had improved recovery outcome, compared with rats treated with repeated injections of standard oxymorphone.     

Assessment of the postoperative discomfort of intra-auricularly hypophysectomized rats

Rats subjected to hypophysectomy make up one of the largest groups of experimental animals in Europe, since there is a legal demand for batch testing of industrially produced growth hormones. To describe the clinical performance of rats having undergone hypophysectomy, animals were examined postoperatively by monitoring behaviour, body temperature and food intake. Behavioural changes were observed in rats that had only been anaesthetized, as well as in sham-operated rats, while no behavioural deviations could be shown in hypophysectomized rats. On the first day after surgery all rats had declining body temperature and food intake; and this change was not reversed by treatment with carprofen, buprenorphine or oxytetracycline. The mortality rate in rats treated with buprenorphine was increased, as was the mortality rate in rats hypophysectomized when weighing more than 100 g. As there seemed to be no differences whether methohexital or a combination of fentanyl, fluanison and midazolam was used, the latter anaesthesia is recommended due to its analgesic potential. For post-surgical analgesic treatment, carprofen is recommended rather than buprenorphine. At best, the use of hypophysectomized rats should be replaced in industrial batch testing by an existing in vitro method.     

"Paradoxical" analgesia and aggravated morphine dependence induced by opioid antagonists

Chronic treatment with naloxone (Nx) or naltrexone (Ntx) induces paradoxical analgesia. In the present study, the effects of chronic treatment with opioid receptor antagonists, such as nor-binaltorphimine (nor-BNI) for kappa and naltrindole (NTI) for delta receptors, on analgesic response using the hot plate test and on morphine physical dependence in rats were examined. The hot plate latency was significantly increased by pretreatment with Nx (5 mg/kg, s.c.), nor-BNI (20 mg/kg, i.p.) or NTI (20 mg/kg, i.p.) for 5 days. After chronic pretreatment with these antagonists, the rats were treated with morphine-admixed food (0.5 mg/g of food) for 3 days. Chronic pretreatment with Nx and NTI significantly increased Nx precipitated body weight loss in morphine dependent rats, while chronic pretreatment with nor-BNI produced small increase. These results indicate that chronic treatment with nor-BNI or NTI as well as with Nx induces obviously paradoxical analgesia, and that chronic blockade of mu or delta may enhance the development of physical dependence on morphine.     

Refinement of the dosage and dosing schedule of ketoprofen for postoperative analgesia in Sprague-Dawley rats

Though ketoprofen is commonly used in rodent surgical procedures, an optimal dosing regimen has not yet been established. The authors sought to refine ketoprofen dosage requirements in rats and to determine whether one or two doses were needed. In one experiment they compared the effects of one preoperative dose of ketoprofen with those of two perioperative doses (3 mg per kg body weight). In a second experiment they compared the effects of two different dosages of ketoprofen (3 or 5 mg per kg body weight). Results show that all regimens tested were similarly effective in curbing post-surgical weight loss and reduction in food and water consumption; therefore, a single dose of 3 mg per kg body weight was the most efficient.