The immune system can influence social motivation with potentially dire consequences for group-housed production animals, such as pigs. The aim of this study was to test the effect of a controlled immune activation in group-housed pigs, through an injection with lipopolysaccharide (LPS) and an intervention with ketoprofen on centrality parameters at the individual level. In addition, we wanted to test the effect of time relative to the injection on general network parameters in order to get a better understanding of changes in social network structures at the group level. 52 female pigs (11–12 weeks) were allocated to four treatments, comprising two injections: ketoprofen-LPS (KL), ketoprofen-saline (KS), saline-LPS (SL) and saline-saline (SS). Social behaviour with a focus on damaging behaviour was observed continuously in 10 × 15 min bouts between 0800 am and 1700 pm 1 day before (baseline) and two subsequent days after injection. Activity was scan-sampled every 5 min for 6 h after the last injection in the pen. Saliva samples were taken for cortisol analysis at baseline and at 4, 24, 48, 72 h after the injections. A controlled immune activation affected centrality parameters for ear manipulation networks at the individual level. Lipopolysaccharide-injected pigs had a lower in-degree centrality, thus, received less interactions, 2 days after the challenge. Treatment effects on tail manipulation and fighting networks were not observed at the individual level. For networks of manipulation of other body parts, in-degree centrality was positively correlated with cortisol response at 4 h and lying behaviour in the first 6 h after the challenge in LPS-injected pigs. Thus, the stronger the pigs reacted to the LPS, the more interactions they received in the subsequent days. The time in relation to injection affected general network parameters for ear manipulation and fighting networks at the group level. For ear manipulation networks, in-degree centralisation was higher on the days following injection, thus, certain individuals in the pen received more interactions than the rest of the group compared to baseline. For fighting networks, betweenness decreased on the first day after injection compared to baseline, indicating that network connectivity increased after the challenge. Networks of tail manipulation and manipulation of other body parts did not change on the days after injection at the group level. Social network analysis is a method that can potentially provide important insights into the effects of sickness on social behaviour in group-housed pigs.

Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, a disease of major impact on pig health, welfare, and productivity globally. Serovar 8 (APP) is the predominant clinical serovar in Norway and the United Kingdom (UK), and has been isolated from clinical cases in Denmark. The primary objective of this study was to characterize the genetic variability of isolates of A. pleuropneumoniae APP8 in the Norwegian population. The secondary objectives were to determine the within-host variability of APP8; to compare the APP8 bacterial populations in Norway, Denmark, and the UK, including antimicrobial resistance (AMR) gene profiles and to assess the effect of national differences in antimicrobial drug use and restricted animal movement on the occurrence of resistance. Isolates of APP8 from the UK (n=67), Denmark (n=22), and Norway (n=123) collected between 1983 and 2020 were compared using whole genome sequencing. To investigate genetic variability within individual hosts, an additional 104 APP8 isolates from the lungs of six Norwegian pigs were compared. Very low within-host variation was observed (≤ 2 single nucleotide polymorphisms). The phylogeny of 123 Norwegian APP8 isolates from 76 herds revealed some within-herd genetic variation, but substantial geographical clustering. When inferring the relatedness of the three international APP8 collections, the topology highlighted the existence of two distinct monophyletic branches characterized by the Norwegian and UK isolates, respectively. Three Danish isolates were scattered across the UK branch, whereas the remaining 19 Danish isolates clustered in two monophyletic groups nested in the Norwegian branch. Coalescence analysis, performed to estimate the divergences from a common ancestor, indicated a last common ancestor several centuries ago. The phylogenetic analyses also revealed striking differences in occurrence of AMR genes, as these were 23-times more prevalent among the UK isolates than among the Norwegian isolates. An increased understanding of the effects of population strategies is helpful in surveillance and control of infectious diseases.

Poor health is a risk factor for damaging behaviors, but the mechanisms behind this link are unknown. Injection of pigs with lipopolysaccharide (LPS) can be used to model aspects of poor health. Recent studies have shown that LPS-injected pigs perform more tail- and ear-directed behavior compared to saline-injected pigs and suggest that pro-inflammatory cytokines may play a role in these behaviors. The aims of this study were to test the effect of LPS on the social behavior of pigs and the neurotransmitters and modulators in their brains and to test the effect of a nonsteroidal anti-inflammatory drug on the effects of LPS. Fifty-two female pigs (11–12 weeks) were allocated to four treatments comprising two injections: saline–saline (SS), saline–LPS (SL), ketoprofen–saline (KS), and ketoprofen–LPS (KL). Activity was scan-sampled every 5 min for 6 h after the last injection in the pen. Social behavior was observed continuously in 10 × 15-min bouts between 8 a.m. and 5 p.m. 1 day before (baseline) and 1 and 2 days after the injection. Saliva was analyzed for cortisol and plasma for tryptophan and kynurenine. The frontal cortex, hippocampus, hypothalamus, and brain stem were sampled 72 h after the injection and analyzed for cytokines and monoamines. LPS activated the HPA axis and decreased the activity within 6 h after the injection. Ketoprofen lowered the effect of LPS on cortisol release and attenuated the behavioral signs of sickness in challenged pigs. SL pigs manipulated the ears of their pen mates significantly longer than SS pigs 2 days after the injection. LPS had no observed effect on IFN-γ, TNF-α, and IL-18. At 72 h after the injection, plasma tryptophan was depleted in SL pigs, and tryptophan and kynurenine concentrations in the frontal cortex and brain stem of SL pigs were significantly lower compared to those in SS pigs. Dopamine concentrations in the hypothalamus of SL pigs were significantly lower compared to those in SS pigs. Serotonin concentrations in the hypothalamus and noradrenaline concentrations in the hippocampus of SL pigs were significantly lower compared to those in KL pigs. In conclusion, LPS influenced the different neurotransmitters and modulators in the brain that are hypothesized to play an important role in the regulation of mood and behavior.

Abstract Background Respiratory diseases are major health concerns in the pig production sector worldwide, contributing adversely to morbidity and mortality. Over the past years there was a rise in reported incidents of respiratory disease in pigs in Norway, despite population wide freedom from Aujeszky´s disease, porcine reproductive and respiratory syndrome, porcine respiratory corona virus and enzootic pneumonia. The main objective of this study was to investigate acute outbreaks of respiratory disease in conventional Norwegian fattening pig herds. The study included 14 herds. In seven herds with reported outbreaks of acute respiratory disease, data on clinical signs was recorded and samples for laboratory examination were collected. Diagnostic protocols were compared by parallel analysis of clinically healthy pigs from seven non-outbreak herds. Results The most commonly reported clinical signs were sudden deaths and dyspnea. An average compartment morbidity of 60%, mortality of 4% and case fatality of 9% was recorded in the outbreak herds. Post-mortem examinations revealed acute lesions resembling porcine pleuropneumonia in all 28 pigs investigated from the outbreak herds and in 2 of the 24 (8%) pigs from the non-outbreak herds. Chronic lesions were recorded in another 2 pigs (8%) from the non-outbreak herds. Actinobacillus pleuropneumoniae serovar 8 was isolated from lungs and/or pleura from all tested pigs (n = 28) in the outbreak herds, and from 2 out of 24 pigs (8%) in the non-outbreak herds, one pig with an acute and another pig with a chronic infection. No other significant bacterial findings were made. Seroconversion to A. pleuropneumoniae antibodies was detectable in all outbreak herds analyzed and in six out of seven non-outbreak herds, but the risk ratio for seroconversion of individual pigs was higher (risk ratio 2.3 [1.50- 3.43 95% CI; P < 0.001]) in the outbreak herds. All herds tested positive for porcine circovirus type 2 and negative for influenza A viruses on oral fluid RT-qPCR. Conclusion The main etiological pathogen found during acute outbreaks of respiratory disease was A. pleuropneumoniae serovar 8. All pigs from outbreak herds had typical lesions of acute porcine pleuropneumonia, and only A. pleuropneumoniae serovar 8 was identified. Co-infections were not found to impact disease development.

Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis. Inflammation was induced in the radiocarpal joint of six horses by injection of 2 ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3 mg) and once with saline. Dexamethasone was quantified by means of UHPLC–MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0–5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration–time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration–response relation in an experimental model of synovitis. The quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.

Studies in mice with ablation of Prnp, the gene that encodes the cellular prion protein (PrPC ), have led to the hypothesis that PrPC is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrPC . Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrPC . Affected nerves were invaded by macrophages and T cells and displayed vacuolated fibers, shrunken axons, and onion bulbs. Peripheral nerve lipid composition was similar in young goats with or without PrPC , but markedly different between corresponding groups of adult goats, reflecting the progressive nature of the neuropathy. This is the first report of a subclinical demyelinating polyneuropathy caused by loss of PrPC function in a nontransgenic mammal.

Most of us have experienced deterioration of mood while ill. In humans, immune activation is associated with lethargy and social withdrawal, irritability and aggression; changes in social motivation could, in theory, lead to less functional interactions. This might also be the case for animals housed in close confinement. Tail biting in pigs is an example of damaging social behavior, and sickness is thought to be a risk factor for tail biting outbreaks. One possible mechanism whereby sickness may influence behavior is through cytokines. To identify possible mediators between immune activation and behavioral change, we injected 16 gilts with lipopolysaccharide (LPS; O111:B4; 1.5 mu g kg(-1) IV through a permanent catheter). In LPS-treated pigs, a significant increase in cortisol, TNF-alpha, IL-1 receptor antagonist, IL-6, and IL-8 was observed alongside decreased activity within the first 6 h after the injection. CRP was elevated at 12 and 24 h after injection, and food intake was reduced for the first 24 h after injection. Three days post-injection, LPS pigs had lower levels of noradrenaline in their hypothalamus, hippocampus and frontal cortex compared to saline-injected pigs. Pigs injected with LPS also had higher levels of the pro-inflammatory cytokine IFN-gamma in their frontal cortex compared to saline-injected pigs. Thus, a low dose of LPS can induce changes in brain cytokine levels and neurotransmitter levels that persist after inflammatory and stress markers in the periphery have returned to baseline levels.

OBJECTIVE:To compare cardiovascular function and response to nociception during total intravenous anaesthesia in pigs with propofol, ketamine and either dexmedetomidine or fentanyl administered as a continuous infusion. STUDY DESIGN:Blinded, randomized, balanced, crossover study ANIMALS: Eight immunocastrated male, mixed breed pigs with a mean ± standard deviation body weight of 26.4 ± 1.9 kg for dexmedetomidine and 27.5 ± 3.8 kg for fentanyl treatment. METHODS:The animals were anaesthetized twice with either propofol-ketamine-dexmedetomidine (DEX) or fentanyl (FENT). DEX was infused at 2, 4 and 8 μg kg-1 hour-1 and FENT at 25, 50 and 100 μg kg-1 hour-1. Each infusion rate was administered for 80 minutes prior to commencing the next. Heart rate (HR), 3-lead electrocardiogram, systolic, mean and diastolic arterial blood pressure (SAP, MAP, DAP) in addition to cardiac output measured by transpulmonary thermodilution was used to monitor cardiovascular function. Mechanical and electrical stimulation (nociceptive withdrawal reflex, NWR) was used to elicit nociceptive responses. Similar anaesthetic depth was determined based on the NWR response. Cardiovascular parameters were compared statistically at this time. Additionally, response to nociceptive stimulation and cardiovascular response over time were compared. RESULTS:DEX-treated pigs had significantly higher HR, SAP, DAP, MAP, systemic vascular resistance, haemoglobin concentration, content of oxygen in arterial and venous blood and oxygen delivery index than FENT-treated pigs at similar anaesthetic depth, whereas stroke volume index was significantly higher in FENT. Motoric response to mechanical nociceptive stimulation was abolished prior to any decrease in NWR response in FENT, whereas the two responses decreased more in unison in DEX. The cardiovascular response to nociception was less pronounced in DEX than in FENT. CONCLUSIONS AND CLINICAL RELEVANCE:Propofol combined with ketamine and either fentanyl or dexmedetomidine provides stable cardiovascular conditions in normovolaemic, healthy pigs. Based on cardiovascular response and depression of NWR, dexmedetomidine apparently provides superior analgesia to fentanyl.

Flunixin is marketed in several countries for analgesia in adult swine but little is known about its efficacy in piglets. Thirty-two piglets (6-8 days old) were randomized to receive placebo saline (n = 11, group CONTROL) or flunixin meglumine intravenously at 2.2 (n = 11, group MEDIUM) or 4.4 (n = 10, group HIGH) mg/kg, 10 hr after subcutaneous injection of kaolin in the left metacarpal area. A hand-held algometer was used to determine each piglet's mechanical nociceptive threshold (MNT) from both front feet up to 50 hr after treatment (cut-off value of 24.5 newton). Serial venous blood samples were obtained to quantify flunixin in plasma using LC-MS/MS. A PKPD model describing the effect of flunixin on the mechanical nociceptive threshold was obtained based on an inhibitory indirect response model. A two-compartmental PK model was used. A significant effect of flunixin was observed for both doses compared to control group, with 4.4 mg/kg showing the most relevant (6-10 newton) and long-lasting effect (34 hr). The median IC50 was 6.78 and 2.63 mg/ml in groups MEDIUM and HIGH, respectively. The ED50 in this model was 6.6 mg/kg. Flunixin exhibited marked antinociceptive effect on kaolin-induced inflammatory hyperalgesia in piglets.

We would like to report rupture of a urinary bladder during manual expression in a male piglet. This event took place at the Norwegian University of Life Sciences in April 2015, during an experimental study investigating haemodynamic parameters in intravenously (IV) anaesthetized experimental piglets. The National Animal Research Authority, ID7236, had approved the study. The piglet was 7 weeks old, 22 kg and an intact male of mixed breed (Norwegian Landrace/Yorkshire). Premedication consisted of ketamine 15 mg kg−1 and midazolam 1 mg kg−1 given intramuscularly (IM). After pre-oxygenation, anaesthesia was induced with 2.7 mg kg−1 propofol IV. The piglet was orotracheally intubated and mechanically ventilated throughout the procedure. Anaesthesia was maintained with propofol 8 mg kg−1 hour−1 and ketamine 5 mg kg−1 hour−1 administered IV. Fentanyl infusion was started at 90 minutes after induction, administered in increasing dose rates of 25, 50 and 100 μg kg−1 hour−1 IV, and maintained for 80 minutes at each rate. Ringer’s Acetate was given IV at 10 mL kg−1 hour−1 throughout the anaesthetic procedure. The anaesthesia was uneventful and lasted for 5.5 hours.

OBJECTIVETo compare cardiac index and oxygen extraction at equivalent depths of anaesthesia between isoflurane-anaesthetized horses and horses anesthetized with isoflurane and dexmedetomidine CRI.STUDY DESIGNSequential, blinded, randomized, balanced, crossover study.ANIMALSEight horses weighing a mean ± standard deviation of 478 ± 58 kg.METHODSHorses were premedicated with 0.03 mg kg(-1) acepromazine intramuscularly (IM) and 8 μg kg(-1) dexmedetomidine intravenously (IV). Anaesthesia was induced with 2.5 mg kg(-1) ketamine and 0.1 mg kg(-1) midazolam IV and maintained with isoflurane in oxygen and air. Horses were mechanically ventilated. Fractional concentration of end-tidal isoflurane (Fe'Iso) was stabilized at 1.7% with a CRI of 0.9% NaCl (IsoNaCl), or at 1.1% with 1.75 μg kg(-1)  hour(-1) dexmedetomidine (IsoDex). Mean arterial blood pressure was maintained above 60 mmHg by dobutamine infusion. Following nociceptive electrical stimulation, Fe'Iso was stabilized at a 0.1% lower concentration and nociceptive stimulation was repeated. This procedure was continued until the horse moved. Fe'Iso values prior to the concentration at which movement occurred were considered to indicate equivalent depths of anaesthesia between treatments. Cardiac index and oxygen extraction were compared at equivalent depths of anaesthesia using a paired Student's t-test.RESULTSCardiac index differed between IsoNaCl at 61 ± 12 mL kg(-1)  minute(-1) and IsoDex at 48 ± 10 mL kg(-1)  minute(-1) (p = 0.047). In addition, oxygen extraction differed between IsoNaCl at 3.4 ± 0.8 mL kg(-1)  minute(-1) and IsoDex at 4.5 ± 0.5 mL kg(-1)  minute(-1) (p = 0.0042). Two horses receiving IsoNaCl were administered dobutamine at equivalent depths of anaesthesia (7.0 and 28.8 μg kg(-1)  hour(-1) , respectively).CONCLUSIONS AND CLINICAL RELEVANCECardiovascular function in horses receiving isoflurane and 1.75 μg kg(-1)  minute(-1) dexmedetomidine is more compromised than in horses receiving a higher concentration of isoflurane and 0.9% NaCl CRI.

A new method for milk sample collection and storage, based on a dried milk sampling technique, is proposed. The method includes application of a whole milk sample to a porous membrane followed by drying. One hundred whole milk samples (dried and liquid) taken on day 21 post insemination were analysed for progesterone by ELISA and results for both dried and liquid samples were well correlated (r = 0.911). Milk progesterone ELISA accuracy for pregnancy diagnosis in cows was 87%.

Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6 µg/kg/h dexmedetomidine IV, with a bolus of 0.96 µg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60 µg/kg/min lignocaine IV, with a bolus of 550 µg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2 µg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15 ng/mL, with a range from <0.02 ng/mL (below the lower limit of quantification) to 0.25 ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60 µg/kg/min, corresponding to plasma lignocaine concentrations >600 ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20 µg/kg/min lignocaine. Lignocaine at 40 µg/kg/min and dexmedetomidine at 4 µg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.

Dexmedetomidine, the most selective α2-adrenoceptor agonist in clinical use, is increasingly being used in both conscious and anaesthetized horses; however, the pharmacokinetics and sedative effects of this drug administered alone as an infusion are not previously described in horses. Seven horses received an infusion of 8 μg dexmedetomidine/kg/h for 150 min, venous blood samples were collected, and dexmedetomidine concentrations were assayed using liquid chromatography-mass spectrometry (LC/MS) and analyzed using noncompartmental pharmacokinetic analysis. Sedation was scored as the distance from the lower lip of the horse to the ground measured in centimetre. The harmonic mean (SD) plasma elimination half-life (Lambda z half-life) for dexmedetomidine was 20.9 (5.1) min, clearance (Cl) was 0.3 (0.20) L/min/kg, and volume of distribution at steady-state (Vdss ) was 13.7 (7.9) L/kg. There was a considerable individual variation in the concentration of dexmedetomidine vs. time profile. The level of sedation covaried with the plasma concentration of dexmedetomidine. This implies that for clinical use of dexmedetomidine constant rate infusion in conscious horses, infusion rates can be easily adjusted to effect, and this is preferable to an infusion at a predetermined value.

After marked airway obstruction with laryngeal mask (LM) placement in neonate piglets, anatomical observations in cadavers revealed a large epiglottis advancing markedly over the soft palate. CT imaging in vivo confirmed that the LM pushes the epiglottis caudally thereby obstructing the larynx. As a new approach, in 20 piglets a flexible PVC bougie placed under laryngoscopy was used to guide the LM to the correct position at the larynx. Placement of the bougie was easy and the LM was positioned successfully in all piglets at first attempt. In 14 piglets, the epiglottis was positioned dorsal to the soft palate before LM insertion and had to be pushed downwards to advance the bougie. In case of failure of LM placement with potential airway obstruction, the use of a bougie to guide the LM over the epiglottis was simple, rapid, and improved the success rate without complication.

OBJECTIVE To elicit and evaluate the NWR (nociceptive withdrawal reflex) in 2 and 11 day old foals, to investigate if buprenorphine causes antinociception and determine if the NWR response changes with increasing age. The effect of buprenorphine on behaviour was also evaluated. STUDY DESIGN Prospective, experimental cross-over trial. ANIMALS Nine Norwegian Fjord research foals. METHODS Buprenorphine, 10 μg kg(-1) was administered intramuscularly (IM) to the same foal at 2 days and at 11 days of age. The NWR and the effect of buprenorphine were evaluated by electromyograms recorded from the left deltoid muscle following electrical stimulation of the left lateral palmar nerve at the level of the pastern. Mentation, locomotor activity and respiratory rate were recorded before and after buprenorphine administration. RESULTS We were able to evoke the NWR and temporal summation in foals using this model. Buprenorphine decreased the root mean square amplitude following single electrical stimulation (p < 0.001) in both age groups, and increased the NWR threshold following single electrical stimulation in 2 day old foals (p = 0.0012). Repeated electrical stimulation at 2 Hz was more effective to elicit temporal summation compared to 5 Hz (p < 0.001). No effect of age upon the NWR threshold was found (p = 0.34). Sedation when left undisturbed (11 occasions), increased locomotor activity when handled (9 occasions) and tachypnea (13 occasions) were common side-effects of buprenorphine. CONCLUSION AND CLINICAL RELEVANCE These findings indicate that buprenorphine has antinociceptive effect in foals. Opioid side effects often recognized in adult horses also occur in foals.