scholarly journals Assessing the affective component of pain, and the efficacy of pain control, using conditioned place aversion in calves

2019 ◽  
Vol 15 (10) ◽  
pp. 20190642 ◽  
Author(s):  
Thomas Ede ◽  
Marina A. G. von Keyserlingk ◽  
Daniel M. Weary
Keyword(s):  
Pain Control ◽  
Time Course ◽  
Control Treatment ◽  
Procedural Pain ◽  
Place Conditioning ◽  
Conditioned Place Aversion ◽  
Duration Of Action ◽  
Place Aversion ◽  
Affective Component ◽  
Conditioning Period

Pain in animals is typically assessed using reflexive and physiological responses. These measures allow inferences regarding nociception but provide little basis for conclusions about the affective component of pain (i.e. how negatively the experience is perceived). Calves routinely undergo painful procedures on commercial farms, including hot-iron disbudding, providing a convenient model to study pain in animals. The aim of this study was to investigate the affective component of post-procedural pain due to hot-iron disbudding, using conditioned place aversion. Calves ( n = 31) were subjected to two procedures (one bud at a time): one without post-procedural pain control and the other with the use of a nonsteroidal anti-inflammatory drug (either meloxicam ( n = 16) or ketoprofen ( n = 15)). All procedures included the use of local anaesthesia (lidocaine). Place conditioning was tested 2 days after the last treatment by allowing calves to freely roam between the pens where they had previously been disbudded. Calves spent more time, and lay down more frequently, in the pen where they received meloxicam compared with the pen where they only received a local block. Surprisingly, calves avoided the pen where they received ketoprofen compared with the control treatment pen. We hypothesize that the shorter duration of action of ketoprofen resulted in increasing pain at the end of the conditioning period, explaining the increased aversion to this treatment. These results illustrate the value of place conditioning paradigms to assess the affective component of pain in animals, and suggest that the animal's evaluation of painful events depends upon the time course of when the pain is experienced.

scholarly journals Genetic Relationships Between Ethanol-Induced Conditioned Place Aversion and Other Ethanol Phenotypes in 15 Inbred Mouse Strains

2019 ◽  
Vol 9 (8) ◽  
pp. 209 ◽  
Author(s):  
Christopher L. Cunningham
Keyword(s):  
Genetic Relationships ◽  
Inbred Mouse ◽  
Genetic Correlations ◽  
Strain Differences ◽  
Mouse Strains ◽  
Place Conditioning ◽  
Conditioned Place Aversion ◽  
Inbred Mouse Strains ◽  
Place Aversion ◽  
Tactile Cues

The genetic relationships between different behaviors used to index the aversive effects of ethanol are unknown. To address this issue, ethanol-induced conditioned place aversion (CPA) was tested in a genetically diverse panel of 15 inbred mouse strains. Mice were exposed to an unbiased place conditioning procedure using ethanol doses of 0, 2, or 4 g/kg; all injections were given immediately after 5-min exposure to distinctive tactile cues. There were dose-dependent effects of ethanol on CPA and on the change in pre-injection activity rates between the first and last conditioning trials. Most strains (80%) developed CPA, demonstrating the generalizability of this behavior. Moreover, genotype had significant effects on CPA magnitude and locomotor activity rates. Strain means from this study and previously published studies were then used to examine genetic correlations. These analyses showed significant genetic correlations between CPA and ethanol intake/preference, conditioned taste aversion, and drug withdrawal (but not blood ethanol concentration or conditioned place preference), supporting the idea of commonality in the genes underlying CPA and each of these behaviors. The overall pattern of findings is consistent with previous data suggesting that genetic differences in sensitivity to ethanol’s aversive effects play a role in determining strain differences in ethanol drinking. The broader implication is that individuals who are more sensitive to the aversive effects of ethanol may be protected from developing the excessive drinking behaviors characteristic of alcohol use disorders.

Stimulation of serotonin 1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats

2002 ◽  
Vol 163 (2) ◽  
pp. 142-150 ◽  
Author(s):  
Luigi Cervo ◽  
Marco Rozio ◽  
Charlotte Ekalle-Soppo ◽  
Francesco Carnovali ◽  
Elisabetta Santangelo ◽  
...  
Keyword(s):  
Place Conditioning ◽  
Conditioned Place Aversion ◽  
Place Aversion ◽  
Stimulation Of

Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients

1996 ◽  
Vol 84 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Shahpoor S. Sorooshian ◽  
Michael A. Stafford ◽  
Nigel B. Eastwood ◽  
Alastair H. Boyd ◽  
Christopher J. Hull ◽  
...  
Keyword(s):  
Muscle Relaxant ◽  
Time Course ◽  
Venous Blood ◽  
The Elderly ◽  
Adult Patients ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Elderly Adult ◽  
Elderly Adults ◽  
Duration Of Action

Background The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect. Methods Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults. Results Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05). Conclusions The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.

scholarly journals Measurement of the dynamics of stimulation and inhibition of steroidogenesis in isolated rat adrenal cells by using column perfusion

1974 ◽  
Vol 142 (2) ◽  
pp. 287-294 ◽  
Author(s):  
P. J. Lowry ◽  
Colin McMartin
Keyword(s):  
Cyclic Amp ◽  
Time Course ◽  
Acth Stimulation ◽  
Duration Of Action ◽  
Adrenal Cells ◽  
Small Column ◽  
Long Duration ◽  
Full Effect ◽  
Rapid Fall

Isolated adrenal cells were perfused in a small column by using Bio-Gel polyacrylamide beads as an inert supporting matrix, and the time-course of the response to various stimuli was observed by measuring fluorogenic 11-hydroxycorticosteroids in the effluent. A small but significant response was observed 1 min after stimulation with physiological concentrations of ACTH (adrenocorticotrophin), but the response did not start to build up rapidly for 3–4min and eventually reached a plateau after 9–10min. A similar pattern of events was observed for the decay of the steroid output on removal of ACTH. ACTH analogues, including one with a long duration of action in vivo, were found to produce responses with similar kinetics. However, cyclic AMP caused a more rapid increase in steroidogenesis and its effects were more short-lived after withdrawal. If, as present evidence suggests, cyclic AMP is produced rapidly after ACTH stimulation the delayed build-up of the steroidogenic response to ACTH would indicate that cyclic AMP may not be the intracellular mediator. When inhibitors were applied during ACTH stimulation, aminoglutethimide, which blocks mitochondrial conversion of cholesterol into pregnenolone (3β-hydroxypregn-5-en-20-one), caused a rapid fall in steroid output (1 min), whereas cycloheximide took longer to achieve its full effect. Nevertheless, the response had fallen by 50% in 2 min, indicating a much shorter half-life than that previously reported for the labile protein implicated in steroidogenesis. In addition the rapid response to cyclic AMP makes it unlikely that steroid production is induced as a result of initiation of protein synthesis. This suggests that the labile protein plays an obligatory but permissive role in the development of the response. Column perfusion has proved to be a simple technique which can readily yield accurate data on responses of cells to stimulants and inhibitors.

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