We conclude that tacrolimus given during 2 weeks in the currently advised dosage has no unfavorable effects on renal hemodynamics and blood pressure in healthy individuals. The use of tacrolimus in organ transplant recipients may in the long-term lead to better renal function and less cardiovascular morbidity than the use of cyclosporine.

Affective states, which refer to feelings or emotions, are a key component of animal welfare, but these are also difficult to assess. Drawing upon a body of theoretical and applied work, we critically review the scientific literature on the assessment of affective states in animals, drawing examples where possible from research on dairy cattle, and highlighting the strengths and weaknesses of scientific methods used to assess affective states in animals. We adopt the "valence/arousal" framework, describing affect as a 2-dimensional space (with valence referring to whether an experience is positive or negative, and arousal referring to the intensity of the experience). We conclude that spontaneous physiological and behavioral responses typically reflect arousal, whereas learned responses can be valuable when investigating valence. We also conclude that the assessment of affective states can be furthered using mood assessments and that the use of drug treatments with known emotional effects in humans can be helpful in the assessment of specific affective states in animals.

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.

Sympathetic overactivity plays a role in the acute hypertensive action of cyclosporine. Cyclosporine given during 2 weeks increases blood pressure and suppresses MSNA, possibly by volume retention. Tacrolimus, in the presently applied dosages, does not cause hypertension or sympathetic overactivity. However, sustained tacrolimus also suppresses sympathetic activity, the reason of which is unclear.

Dairy calves are routinely disbudded by cauterization with a hot iron. To mitigate the intra-operative and initial post-operative pain associated with this procedure some farmers provide calves general and local anesthetics, but it is unknown if the procedure remains aversive. We used a place-conditioning paradigm to assess aversion caused by hot-iron cautery with a local anesthetic compared to a sham procedure. A test area was divided into three equally sized pens: two ‘treatment’ pens with distinct visual cues were connected by a central ‘neutral’ pen. Each calf went through the disbudding procedure and a 6-h recovery period in one treatment pen and the control procedure in the other treatment pen. In three tests (48, 72 and 96 h after the second treatment), calves could freely roam among the pens until they chose to lie down, ending the session. Calves spent less time in either of the treatment pens compared to the central pen. When only comparing the two treatment pen, calves spent less time in the disbudding pen, especially during the first test. Calves were also less likely to lie down in the pen associated with the disbudding procedure. We conclude that even with the use of a local anesthetic, hot-iron disbudding is salient and aversive for calves, indicating the need to refine or avoid the procedure.

We assessed aversion to injections using an avoidance-learning paradigm. Holstein calves (n = 24) were randomly assigned to one of four routes of administration for 0.5 ml of saline: intramuscular (IM), intranasal (IN), subcutaneous (SC) and a null control. Calves were first trained to approach a milk reward of 1 L. Once the latency to approach the reward was consistent, calves received their assigned treatment when approaching the bottle. For the first 3 treatment sessions calves received a 1 L milk reward. This reward was then reduced to 500 mL, and then to 250 mL, and finally to 0 mL, each for 3 sessions. Compared to control calves, calves receiving the intramuscular injections showed a longer latency to approach the milk reward, but only when the milk reward was 0.25 L (P = 0.05) and 0 L (P < 0.01). Calves receiving the intranasal injections showed longer latencies relative to the controls only for the 0 L reward (P = 0.01). Calves receiving the subcutaneous injections did not differ from controls for any of the milk rewards (P > 0.2). We conclude that IM injections are aversive and that SC and IN routes are a refinement to be considered when feasible.

No abstract

Despite scientific interest in animal empathy, and growing public concern for farm animal welfare, the empathic abilities of farm animals remain under researched. In this study, we investigated empathic responses of young Holstein dairy calves to conspecifics recovering from hot-iron disbudding, a painful procedure common on dairy farms. A combination of social approach and place conditioning was used. First, 'observer' calves witnessed two 'demonstrator' calves recover from either a painful procedure (hot-iron disbudding and sedation) or a sham procedure (sedation alone) in distinct pens. Observer calves spent more time in proximity and paid more attention to calves recovering from the painful procedure compared to sham calves (proximity: 59.6 ± 4.3%; attention: 54.3 ± 1.5%). Observers were then tested for conditioned place aversion (in the absence of demonstrators) at 48h, 72h and 96h after the second demonstration; observers tended to avoid the pen associated with conspecific pain during the second of the three tests, spending 34.8 ± 9.6% of their time in this pen. No strong evidence of pain empathy was found, but our tentative results encourage further research on empathy in animals.