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Surgical Stress in Rats : The Impact of Buprenorphine on Postoperative Recovery
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During surgery, both anesthesia and tissue damage cause physiological stress responses in the body. The hypothalamic-pituitary-adrenal (HPA) axis is activated with increased levels of glucocorticoids. After surgical procedures the stress response may be a cause of postoperative morbidity and pre-emptive analgesic treatment can attenuate the stress response during the postoperative period. In laboratory animals, buprenorphine is a commonly used analgesic. Subcutaneous (s.c.) administration of buprenorphine is most common, but oral administration would be preferable in many cases, enabling administration without any handling of the rat.

In this thesis we studied the surgical stress response in laboratory rats during surgery and in the postoperative period, and its modulation by s.c. injection and oral voluntary ingestion (VI) of buprenorphine. Corticosterone levels and the clinical parameters body weight, water intake and behavior were observed. The concentration of buprenorphine in plasma was measured as well as stock-related differences in postoperative recovery.

During surgery and anesthesia there was a higher corticosterone release during a more severe surgery and corticosterone levels were reduced more effectively after buprenorphine treatment than after lidocaine treatment.

Buprenorphine treatment, independent of the route of administration, led to better postoperative recovery in body weight and water intake compared to local anesthetics. VI of buprenorphine resulted in a suppression of plasma corticosterone levels compared to s.c. buprenorphine treatment and treatment with local anesthetics during the first day after surgical catheterization. The corticosterone levels of all buprenorphine treated groups had, by the second postoperative day, reverted to the normal diurnal rhythm of corticosterone secretion. Buprenorphine treatment increased locomotor activity in non-operated rats only. The effect of buprenorphine in operated rats could not be detected via the monitoring of locomotor activity or the time spent resting in the present study.

Treatment with buprenorphine by VI has similar effects on postoperative plasma corticosterone levels in both Wistar and Sprague-Dawley rats. VI of buprenorphine resulted in a buprenorphine concentration in plasma at least as high as by s.c. treatment.

Thus, administration by VI of buprenorphine appears to be an effective stress-reducing method for administrating postoperative analgesia to laboratory rats.

Place, publisher, year, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 849
Keyword [en]
Surgical stress, Corticosterone, Buprenorphine, Analgesia, Rats.
National Category
Other Basic Medicine
Research subject
Comparative Medicine
Identifiers
urn:nbn:se:uu:diva-185686 (URN)978-91-554-8558-0 (ISBN)oai:DiVA.org:uu-185686 (OAI)diva2:574121 (DiVA)
Public defence
2013-02-01, BMC, B22, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from2013-01-11 Created:2012-11-27 Last updated:2013-04-02
List of papers
1. Effect of subcutaneous injection and oral voluntary ingestion of buprenorphine on post-operative serum corticosterone levels in male rats
Open this publication in new window or tab >>Effect of subcutaneous injection and oral voluntary ingestion of buprenorphine on post-operative serum corticosterone levels in male rats
2008 (English)In: European Surgical Research, ISSN 0014-312X, E-ISSN 1421-9921, Vol. 41, no 3, 272-278Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Adequate peri-operative analgesia may reduce post-operative stress response and improve recovery in laboratory animals. We have established a method involving repeated automated blood sampling, allowing quantification of serum corticosterone levels in rats for stress assessment without stress-inducing handling or restraint. In the present study, the effects of the commonly used route of buprenorphine administration (0.05 mg/kg injected subcutaneously) were compared with oral administration (0.4 mg/kg mixed with Nutella and orally administered by voluntary ingestion) in male Sprague-Dawley rats. METHODS: A catheter was placed in the jugular vein and attached to an Accusampler for automated blood sampling. During 96 h after surgery, blood was collected at specified time points. Pre- and post-operative body weights and water consumption were registered. RESULTS: Buprenorphine significantly suppressed levels of circulating corticosterone after the oral but not after the subcutaneous treatment. Both buprenorphine treatments had a positive impact on maintenance of body weight and water consumption, compared to the control group that received no buprenorphine. CONCLUSION: The present investigation suggests that oral voluntary ingestion ad libitum is an efficacious, convenient and non-invasive way of administering peri-operative buprenorphine to rats, as judged by corticosteroid response and effects on body weight and water consumption.

Keyword
Surgical stress, Analgesia, Rats
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-102299 (URN)10.1159/000142372 (DOI)000260241300004 ()18596376 (PubMedID)
Available from2009-05-06 Created:2009-05-06 Last updated:2013-02-11Bibliographically approved
2. Impact of Surgical Severity and Analgesic Treatment on Plasma Corticosterone in Rats during Surgery
Open this publication in new window or tab >>Impact of Surgical Severity and Analgesic Treatment on Plasma Corticosterone in Rats during Surgery
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2010 (English)In: European Surgical Research, ISSN 0014-312X, E-ISSN 1421-9921, Vol. 44, no 2, 117-123Article in journal (Refereed) Published
Abstract [en]

Tissue injury and anaesthesia during surgery induce a stress response associated with increased glucocorticoid secretion from the adrenal glands. This response alters the normal physiology and may cause postoperative morbidity, as well as affect the results during acute experiments. The aim of the present investigation was to study the effect of surgical severity and analgesic treatment on circulating corticosterone in male Sprague-Dawley rats. Male rats were treated with either lidocaine infiltrated during surgery, buprenorphine (0.05 or 0.1 mg/kg subcutaneously) or saline subcutaneously. Each treatment group was subjected to either arterial catheterisation or arterial catheterisation and laparotomy. A catheter was inserted in the common carotid artery and blood was collected during surgery and during anaesthesia 6 h after surgery. Lidocaine treatment reduced the corticosterone levels compared to saline treatment after catheterisation but not after laparotomy. Buprenorphine treatment reduced the corticosterone levels during the first hour after surgery after both catheterisation and laparotomy. The higher buprenorphine dose led to an earlier and more pronounced reduction, especially after laparotomy. In the present study, the corticosterone response during surgery in laboratory rats is correlated with the severity of the procedure, and buprenorphine reduces the surgical stress response more effectively than lidocaine treatment.

Keyword
Surgical stress, Corticosterone, Analgesia, Lidocaine, Buprenorphine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-144507 (URN)10.1159/000264962 (DOI)000275045800007 ()20145406 (PubMedID)
Available from2011-02-01 Created:2011-01-31 Last updated:2013-02-11Bibliographically approved
3. Effects of Voluntarily-ingested Buprenorphine on Plasma Corticosterone Levels, Body Weight, Water Intake, and Behaviour in Permanently Catheterised Rats
Open this publication in new window or tab >>Effects of Voluntarily-ingested Buprenorphine on Plasma Corticosterone Levels, Body Weight, Water Intake, and Behaviour in Permanently Catheterised Rats
2010 (English)In: In Vivo, ISSN 0258-851X, Vol. 24, no 2, 131-135Article in journal (Refereed) Published
Abstract [en]

This study investigated the peri- and postoperative effect of pre-emptive analgesia through voluntary ingestion of buprenorphine in Nutella (R), in male Sprague-Dawley rats. An arterial catheter was inserted and the rats were connected to an automated blood sampling device (AccuSampler (R)). Blood samples were drawn up to 18 h after surgery and the plasma concentrations of corticosterone were quantified. Postoperative changes in water intake and body weight were recorded, and the behaviour of the rats was analysed during two 30-min periods. Pre-emptive oral buprenorphine treatment reduced the plasma corticosterone levels in the postoperative period, compared to controls treated with local anaesthetics. Buprenorphine-treated rats consumed more water and maintained body weight better. Behavioural observations indicated that buprenorphine changed the behaviour in non-operated rats but there was no difference in the operated rats. The present study strengthens the hypothesis that pre-emptive oral buprenorphine in Nutella is suitable for treatment of postoperative pain in rats.

Keyword
Buprenorphine, surgery, corticosterone, behaviour, rats
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-136659 (URN)000275974100002 ()20363983 (PubMedID)
Available from2010-12-14 Created:2010-12-14 Last updated:2013-02-11Bibliographically approved
4. Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization
Open this publication in new window or tab >>Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization
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2010 (English)In: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, Vol. 44, no 4, 337-343Article in journal (Refereed) Published
Abstract [en]

The present study investigated the postoperative plasma concentrations of corticosterone and buprenorphine in male Wistar and Sprague-Dawley rats, treated with buprenorphine administered either through subcutaneous (SC) injection or through voluntary ingestion (VI). The animals were treated with buprenorphine for pre-emptive analgesia prior to surgical placement of a jugular catheter, followed by automated blood sampling during 96 h. Buprenorphine was administered on a regular basis throughout the experiment, and blood was collected on selected time points. Body weight was measured before and 96 h after surgery. It was found that the two rat stocks responded in a similar manner to both buprenorphine treatments, with the exception of body weight change in Wistar rats, in which body weight was reduced after SC treatment. The plasma concentration of corticosterone was significantly higher in the SC-treated animals than in the VI-treated animals during the first 18 h of the study, while plasma buprenorphine concentration was at least as high and more even over time after VI treatment. The present study shows that buprenorphine administration through VI is suitable for both Wistar and Sprague-Dawley rats, with lower stress response and higher plasma concentrations of buprenorphine than after the traditional SC route of administration.

Keyword
Rats, catheterization, analgesia, buprenorphine, surgical stress, corticosterone
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:uu:diva-133727 (URN)10.1258/la.2010.009115 (DOI)000283457500008 ()
Available from2010-11-18 Created:2010-11-15 Last updated:2013-02-11Bibliographically approved

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