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Use of an analgesic to identify pain-related indicators of lameness in sows
Livestock Science 180 (2015) 203–208
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Use of an analgesic to identify pain-related indicators of lameness in sows S. Conte a, R. Bergeron b, H. Gonyou c, J. Brown c, F.C. Rioja-Lang c, M.L. Connor d, N. Devillers a,n a
Agriculture and Agri-Food Canada, Dairy and Swine R&D Centre, Sherbrooke, QC, Canada, J1M 0C8 University of Guelph, Alfred Campus, Alfred, ON, Canada, K0B 1A0 c Prairie Swine Centre, Saskatoon, SK, Canada, S7H 5N9 d University of Manitoba, Department of Animal Science, Winnipeg, MB, Canada, R3T 2N2 b
art ic l e i nf o
a b s t r a c t
Article history: Received 5 March 2015 Received in revised form 25 August 2015 Accepted 26 August 2015
Lameness in sows may be associated with pain and poor welfare and requires early detection and treatment. The objective of this study was to use the non-steroidal anti-inflammatory drug meloxicam, as a short-term analgesic to identify characteristics of pain-related lameness in sows. A total of 44 pregnant sows were selected from two experimental sites, and used in a 2 2 factorial design. Sows were visually categorized as either non-lame or lame (none with severe lameness), and were either assigned to a placebo (saline) or meloxicam (0.4 mg/kg body weight) treatment. Lameness was assessed using a force plate, kinematic and accelerometer tools on the day before, and after a single intramuscular injection of treatment solution. Data were collected in the same order and at the same time on both days, starting at 7:45, 9:15 and 12:15 for accelerometers, force plate and kinematics, respectively. Before treatment, lame sows made a greater number of steps per min than sound sows (P ¼0.013), and had a tendency to have a lower contralateral ratio of weight applied between the hind legs than sound sows (P¼ 0.062). No other differences were observed between lame and sound sows before treatment. Injection of meloxicam decreased the stepping frequency of the left hind legs (P ¼0.014), increased the ratio of tarsal joint angle amplitude between contralateral hind legs (P¼ 0.05), and tended to increase standing time after feeding in lame sows (P ¼0.09), indicating an improvement of the lameness condition and at least a short-term analgesic effect of meloxicam. Overall, meloxicam effects on lameness variables were limited. The wide variability in the underlying clinical causes, severity and duration of these naturally occurring lameness cases, as well as the timing of lameness assessment in relation to treatment injection may explain the relative lack of treatment effects on kinematics and force plate variables. More research is needed to identify pathology-specific indicators of pain-related lameness. Crown Copyright & 2015 Published by Elsevier B.V. All rights reserved.
Keywords: Accelerometers Force plate Kinematics Lameness Meloxicam Sow
1. Introduction Early detection of lameness is important to provide prompt treatment and hence improve welfare (Flower et al., 2005). Lameness can have multiple origins in sows: osteochondrosis, arthritis, osteoarthritis, osteomyelitis, abscesses, bursitis, and various claw lesions and leg injuries (Heinonen et al., 2013). In finisher pigs, experts have associated causes of lameness with various degrees of pain, and ranked fractures, osteochondrosis dissecans and infectious arthritis as most painful (Jensen et al., 2012). Research to identify and validate pain indicators in sows is very limited despite the necessity to recognise pain-related lameness n
Corresponding author. Fax: þ 1 819 564 5507. E-mail address: [email protected] (N. Devillers).
http://dx.doi.org/10.1016/j.livsci.2015.08.009 1871-1413/Crown Copyright & 2015 Published by Elsevier B.V. All rights reserved.
for welfare reasons. In cows, changes in behaviour or gait following the administration of an analgesic were difficult to identify, while differences in weight distribution on a force plate were observed (Chapinal et al., 2010a, 2010b; Flower et al., 2008; Whay et al., 2005). Whay et al. (2005) hypothesised that behavioural expression of pain is likely to be very subtle and suggested that more work is required to determine behaviours that would be indicators of pain in lame animals. The use of automated methods such as accelerometers to measure stepping, kinematics or force plate (Conte et al., 2014; Grégoire et al., 2013) may help identify subtle changes in the gait and postural behaviour after alleviating pain compared to visual observation. In Europe and Canada, a nonsteroidal anti-inflammatory drug (NSAID) called meloxicam, sold s under the product name Metacam , is licensed for the treatment of lameness in pigs at a dose of 0.4 mg/kg i.m. In dogs and chickens, meloxicam is considered as the drug of choice to treat
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osteoarthritis and joint inflammatory diseases (Cross et al., 1997; Hadipour et al., 2011; Peterson and Keefe, 2004). To our knowledge, very few published studies have assessed the effect of meloxicam on swine lameness. Friton et al. (2003) found a reduction in lameness days after the injection of meloxicam in pigs (gilts, sows and finishers), using a scoring system based on the observation of weight-bearing on limbs. More recently, Pairis-Garcia et al. (2014) demonstrated the effectiveness of meloxicam at reducing pain in sows with induced lameness, using nociceptive threshold tests. The aim of the present project is to use meloxicam as a shortterm analgesic to identify, using quantitative methods (force plate, kinematics and accelerometers), characteristics of pain-related lameness in sows that are mildly and moderately lame.
2. Materials and methods Animals were cared for according to the Canadian Council on Animal Care guidelines (Canadian Council on Animal Care, 2009) and a recommended code of practise (Agriculture and Agri-Food Canada, 1993) and the experimental protocol was approved by the institutional animal care committee of the Dairy and Swine R&D Centre (Sherbrooke, Quebec, Canada) and the University of Saskatchewan's Animal Research Ethics Board (Saskatoon, Saskatchewan, Canada). 2.1. Animals and treatments A total of 44 primiparous (n ¼5) and multiparous (n ¼39) Landrace Yorkshire sows (267734 kg BW) were selected from the Dairy and Swine R&D Centre (DSRDC, n ¼16; Sherbrooke, Quebec, Canada) and the Prairie Swine Centre Inc. (PSC, n ¼28; Saskatoon, Saskatchewan, Canada) and used in a 2 2 factorial design. Sows were housed in individual pens of 2.97 m2 (DSRDC) or in groups of approximately 30 animals with walk-in/lock-in feeding stalls (PSC), both with partially slatted concrete floors. Once per week (n ¼11), four sows (from the same group at PSC) between 29 and 76 days into gestation were selected according to the following criteria: no obvious leg injuries or severe lameness, and not medicated with non-steroidal anti-inflammatory drugs, glucocorticoids or antibiotics within the previous 14 days before the experiment (Friton et al., 2003; Mustonen et al., 2011). Using a visual gait scoring system adapted from Main et al. (2000), sows were individually scored, while walking in a corridor on plain concrete floor, on a scale from 0 to 4 (0: normal gait and even strides; 1: abnormal gait, stiffness, but lameness not easily identified; 2: lameness detected, shortened strides, sow puts less weight or avoids putting weight on one leg; 3: sow does not bear weight on one leg; 4: non-ambulatory) and then categorized as sound (score 0, n ¼21) or lame (score 1, n ¼5 or score 2, n¼ 18). Sows scored 3 or 4 were not selected because the study aimed at validating pain-related criteria for early identification of lameness. Therefore, sows that were obviously in pain and non-ambulatory were excluded. Two lame and two sound sows were selected each week. The day after visual scoring, gait score was visually confirmed and lameness was assessed using the force plate, kinematics and accelerometers tools, as previously described (Conte et al., 2014; Grégoire et al., 2013; Ringgenberg et al., 2010). Then, sows were put back in their home pen. On the following day, the two lame and two sound sows were assigned randomly to either meloxicam s treatment (Metacam , Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany) or a placebo treatment (saline solution), to which the experimenter was blind and lameness was assessed again using the same methods in the same order. The
dose of meloxicam of 0.4 mg/kg body weight recommended by the manufacturer (20 mg/ml, 0.02 ml/kg) was administered as a single intramuscular injection in the neck region at 7:15. Stepping behaviour, weight distribution and gait were measured on each sow within an 8 h-period after the i.m. injection. In sows, the time to reach the maximum plasma concentration (Tmax) after per os administration of 0.5 mg/kg of meloxicam was 2.4 h, and half-life (T1/2) was 6.83 h, while the i.v. half-life was 6.15 h (Pairis-Garcia et al., 2014a). When 0.6 mg/kg were administered i.m. to piglets, Tmax ranged from 0.4 to 1.8 h (Fosse et al., 2011). Therefore, measurements in the present experiment were likely performed around the time at which the drug was the most effective. Data were collected in the same order and at the same time on both days (day before and day of treatment), starting at 7:45, 9:15 and 12:15 for accelerometers, force plate and kinematics, respectively. All measurements were recorded by the same experimenter. The number of sows was initially balanced between treatments within experimental farms but one sow was moved a posteriori from the Sound-Meloxicam to the Lame-Meloxicam group because her lameness score increased between the day of selection and the day before treatment. Therefore, numbers of sows per treatment were 12 for Lame-Meloxicam, 11 for Lame-Placebo, 10 for Sound-Meloxicam and 11 for Sound-Placebo. 2.2. Measurements and calculations 2.2.1. Accelerometers Acceleration recordings were made for 1 h following the start of feeding to determine the number of steps per min while the sow stood, following a procedure previously used (Conte et al., 2014). Sows were fed in a trough within their individual pen (DSRDC) or in a feeding stall (PSC) where they were kept for 1 h. s One accelerometer (Hobo Pendant G Data Logger, Onset Computer Corporation, Pocasset, MA, USA), safely protected inside a Velcros-pocket and a VetrapTM 3MTM covering, was placed on each hind leg. The device recorded the acceleration on the x-axis (10 data per second), for 1 h. A step was considered true if the xaxis acceleration was o0.6 g or 4 1.4 g (Ringgenberg et al., 2010), while the animal was in a standing position. The latency to lie down after feed delivery, corresponding to acceleration on the xaxis o0.59 g, was also determined. Data from recordings were s read using the Hoboware Pro software (Onset Computer Corporation, Pocasset, MA, USA). 2.2.2. Force plate The force plate (Pacific Industrial Scale Co. Ltd., Richmond, BC, Canada) consisted of four individual stainless steel platforms (front: 101.6 30.5 cm2, rear: 111.8 30.5 cm2), each resting on four single-ended beam load cells. A feeder was included on the front gate to draw the sow's attention towards a standardized direction. The total weight and the weight placed on each platform (14 data per second) were recorded and saved using the Pacweight Animal Weight custom software (Pacific Industrial Scale Co. Ltd.). Two cameras were used to record the position of the sow's legs using the Omnicast video surveillance system (Genetec Inc.©, version 4.6, 2001–2012, Montreal, Quebec, Canada), which was synchronized with the Pacweight Animal Weight custom software. Sows were measured for a period of 15 min, but only periods when the sow stood with her head in the feeder and her legs in the correct platform were kept and any body weight per reading higher or lower than 5% of the average body weight of the sow was eliminated as previously described (Conte et al., 2014). For each leg, the average percentage of weight (% BW) was calculated. The average ratio of lower to higher weight applied by contralateral legs was calculated separately for fore and hind legs (contralateral ratio). Weight shifting was evaluated according to
S. Conte et al. / Livestock Science 180 (2015) 203–208
the same method previously described (Conte et al., 2014) and frequency of weight shifting per min (WS), percentage of time WS (% of time WS) and amplitude of WS (% BW) were calculated. 2.2.3. Kinematics Each sow was equipped with fifteen reflective markers placed in standardised locations on the body and was video recorded while walking along a corridor 7.3 m long and 1.1 m wide (plain concrete floor type). The detailed procedure has previously been described by Conte et al. (2014). Each side of the sow was recorded s separately with a DFK22AUC03 camera (The Imaging Source Europe GmbH, Bremen, Germany) with lens (Pentax CCTV C418DX, 4.8 mm, 1: 1.8, Pentax Ricoh Imaging Americas Corporation, Denver, CO, USA) using the IC Imaging Capture 2.2 software (The Imaging Source Europe GmbH, Bremen, Germany). Gait chars acteristics were analysed using the motion analysis MoviAS Pro software (NAC Image Technology, Simi Valley, USA). The data measured for each leg were stance time, swing time, foot height, stride length, average angle and amplitude of joints angle for the carpal joint for fore leg, and the tarsal joint for hind leg during the swing and stance periods. The average value from 3 individual steps was used in the analysis. 2.3. Statistical analyses The frequency of stepping behaviour for right leg and left leg separately, the average frequency of stepping (between right and left legs), and the latency to lie down after feeding were analysed using the Kruskal–Wallis test for period before the injection, with state (lame vs. sound) and solution (meloxicam vs. placebo) in the model, and then with the four treatments in the model. The delta values (difference between the measure after and before the injection) for the above variables were calculated and analysed using the Kruskal–Wallis test with the four treatments in the model. Data are presented in the text as median with lower–upper quartiles between brackets. Correlations between left and right legs measures from the force plate and the kinematics were done. Variables with a significant positive correlation between right and left legs were averaged for fore and hind legs separately (frequency of WS, % of time WS, amplitude of WS, stride length, swing and stance time). For variables with negative or no correlation between right and left legs, a ratio (lowest value/highest from the right and left legs) was calculated for front and hind legs separately (foot height, carpal and tarsal angle during swing and stance phase, carpal and tarsal angle amplitude during swing and stance phase) in order to measure asymmetry. The MIXED procedure was used on measures that were averaged between right and left legs, with the state (lame vs. sound) and the solution (meloxicam vs. placebo) in the model. The GLIMMIX procedure with a beta distribution and a logit link function was used on ratios with the state and the solution in the model. The analyses were firstly done separately for measures before and after injection, then using a model with the period (before vs. after injection) as repeated measures and the four treatments (Lame-Meloxicam, Lame-Placebo, Sound-Meloxicam, Sound-Placebo) in the model. Data from the MIXED procedure are presented as least square mean 7maximum SEM. Data from the GLIMMIX procedure are expressed as back transformed least square mean with the confidence interval between square brackets.
3. Results and discussion The present study partly confirms previous results on the usefulness of some variables for the differentiation between lame
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and sound sows. Before treatment, lame sows made a greater number of steps per min than sound sows (6.5 (4.3–7.4) vs. 3.3 (2.2–6.4), respectively, P ¼0.013). This difference existed for both right (5.3 (4.3–8.3) vs. 3.2 (2.3–5.4), respectively; P ¼0.018) and left hind legs (6.5 (3.3–8.4) vs. 3.7 (2.4–7.1), respectively; P¼ 0.07) and are in accordance with Grégoire et al. (2013). Lame sows also had a tendency to have a lower contralateral ratio of weight applied on the hind legs than sound sows (0.66 [0.61–0.71] vs. 0.72 [0.68–0.76], respectively; P ¼0.062), as already shown by Conte et al. (2014). However, no additional differences were observed between lame and sound sows before treatment for force plate and kinematics measurements (data not shown; P4 0.10), as expected from the same previous studies. In contrast to what has been previously observed by Grégoire et al. (2013), there was no significant difference between lame and sound sows for the latency to lie down following feeding (46.1 min (28.3–60.0) vs. 54.8 min (36.7–60.0), respectively; P¼ 0.16). Force plate measurements did not show significant differences in weight shifting values contrary to the results from Conte et al. (2014). Finally, there were no variations in gait parameters such as a shorter stride length or a longer stance time in lame sows (Grégoire et al., 2013; Mohling et al., 2014). These few differences between lame and sound sows before any treatment unfortunately lower the potential of the present study to detect an effect of meloxicam. It should be noted that lame sows in the present study presented lower lameness scores than those of Grégoire et al. (2013) and Conte et al. (2014), because the focus was on lameness cases that were not obviously painful. In line with the lack of differences in gait and weight distribution between lame and sound sows, our study did not succeed in demonstrating a clear and significant short-term effect of the injection of meloxicam on most measured variables. Nevertheless, injection of meloxicam significantly decreased the stepping frequency of the left hind leg as shown by the negative delta value between after and before the injection for Lame-Meloxicam sows (Fig. 1). This negative delta value indicates an improvement of Lame-Meloxicam sows' condition. It also suggests that most of these sows probably had a painful left hind leg. Indeed, considering lame and sound sows separately, lame sows receiving the meloxicam showed a significant improvement in the stepping frequency compared to sows receiving a placebo, whose condition deteriorated (P¼ 0.031). In contrast, there was no difference for sound sows (P¼ 0.79). This effect, only observed on left hind legs, highlights the fact that sow distribution between treatments in terms of pathology underlying lameness or which leg was painful was not balanced. This also confirms the challenge of studying lameness in naturally lame sows without being able to diagnose the cause of lameness and the legs affected. Despite the lack of differences before treatment, there was a tendency for a difference between the four treatments in the delta value for the latency to lie down (Lame-Meloxicam: 3.7 (0–11.4), Lame-Placebo: 0 ( 15.8 to 2.4), Sound-Meloxicam: 0 ( 6.1 to 0.7), Sound-Placebo: 0 ( 21.8 to 0) min; P ¼0.09), indicating that lame sows receiving meloxicam were standing for a longer time following feeding after the injection compared to the day before. Finally, a significant interaction between treatments and period was found for the ratio of angle amplitudes of carpal and tarsal joints during swing time (Table 1). The ratio of angle amplitude between contralateral legs of lame sows receiving meloxicam was reduced in fore legs after injection, while it was increased for hind legs. An increase in the ratio would mean a better symmetry of the movement between contralateral legs, and potentially an improvement of the lameness condition. This improvement would support the fact that most lame sows were affected at hind legs and that meloxicam had an effect on alleviating pain related to walking. Beyond these few differences, there were no significant
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Fig. 1. Effect of the injection of meloxicam (Mlx) or a placebo (Pcb) on the stepping frequency of lame and sound sows (boxplot (min, 1st quartile, median, 3rd quartile, max) for delta values calculated as after minus before the injection).
interactive effects of treatments and period, which would indicate an effect of meloxicam, on variables measured with the force plate for the fore or hind legs (P 40.10, Table 2) and most of the variables measured with kinematics for the fore or hind legs (P 40.10, Table 2). Pairis-Garcia et al. (2014) showed a significant improvement in pain sensitivity to pressure from 7.5 h after oral administration of meloxicam (1 mg/kg), which corresponds to T1/2, but not at Tmax (i.e. 2 h after administration) in sows with an induced lameness. On the other hand, they saw a significant improvement in pain sensitivity to focussed radiant heat stimulation at Tmax but not during the following 24 h. Pairis-Garcia et al. (2015) also showed a reduction in lying posture frequencies 24 h after meloxicam treatment. Friton et al. (2003) observed an improvement in clinical lameness score at rest and while walking 24 h post-injection (0.4 mg/kg i.m.). In the present study, the main effect, observed as a decrease in the stepping frequency and a longer period standing, occurred at a time when the drug concentration had likely reached its maximum value. Previous studies on the use of meloxicam to alleviate pain following castration in piglets showed its effectiveness in reducing physiological and behavioural indicators of pain in the first hour following the procedure (Hansson et al., 2011; Keita et al., 2010). According to our results, stepping frequency could be related to pain sensitivity and, in accordance with previous studies (Conte et al., 2014; Grégoire et al., 2013; Pluym et al., 2013), would make a promising indicator of pain-related lameness. However, the present study did not succeed in determining specific pain-related indicators of naturally occurring lameness using the force plate and the kinematics methodologies that would help in identifying the affected leg. Lameness is a multifactorial problem and the wide variations observed between sows in their gait, weight distribution and postural behaviour could depend on the underlying clinical cause, its severity and the number of legs affected. Because it is very difficult to make an accurate diagnosis on live animals, the experimenter was not able to know the clinical cause of lameness and its severity. It should also be noted that sows were not monitored over a long period of time prior to the start of the experiment. Therefore, it was not possible to determine whether selected sows were suffering from acute or chronic pain. In horses suffering from laminitis, persistent pain may lead to a decrease in effectiveness of analgesic protocols (Jones et al., 2007). In addition, it could be hypothesised that sows suffering from a chronic condition may have habituated to their antalgic gait, and may have required more time to resume their normal posture and gait following analgesia. Although sows
served as their own control, selection of sows based only on a global visual score possibly introduced large variations in the cause, severity and duration of lameness, and in the number of legs affected, which may have masked the effect of meloxicam. To solve this problem, the use of an induced lameness model allowing a better standardisation of the type of lameness would help to assess the effectiveness of analgesics as demonstrated by PairisGarcia et al. (2014) and Tapper et al. (2013). However, the validity of such model to simulate naturally occurring lameness can still be questioned, especially for chronic pathologies such as arthritis or osteochondrosis. The ability to select animals affected by the same pathology would also improve standardisation and homogeneity of symptoms and results as observed in cows (Pastell et al., 2010). The effectiveness of meloxicam to relieve lameness pain in the short-term is still questioned in sows as its analgesic properties are related to its anti-inflammatory action and may take several hours to be noticeable. In the study by Friton et al. (2003), lameness assessment in sows was not done in the period of time immediately following i.m. administration of 0.4 mk/kg of meloxicam, but only 24 h after. Drugs that more specifically target neuropathic pain, such as gabapentin, could be useful to specifically identify characteristics of pain-related lameness (Coetzee et al., 2014). Finally, it is possible that the recommended dose used in the present study was not sufficient for the drug to reach its maximum pain-relieving effect. In their study on nociceptive thresholds following administration of meloxicam, (Pairis-Garcia et al., 2014), used a dose of 1 mg/kg, but it was administered orally. More research on the pharmacokinetics of meloxicam in sows following i.m. administration would be necessary to extrapolate from their results.
4. Conclusion Meloxicam i.m. injection to lame sows resulted in a decrease in the stepping frequency measured with accelerometers, and a better symmetry of hind legs movement as measured by the ratio of angle amplitude between contralateral hind legs. All other variables were unaffected by treatment. Timing of lameness measurement with force plates and kinematics in relation to meloxicam treatment may explain its lack of effect. Further research is still needed to identify specific pain-related indicators of lameness in naturally lame sows and more specifically on the development of tools or indicators to identify pathologies or affected legs on live animals.
Table 1 Effect of Meloxicam or placebo injections on kinematics and force plate variables measured on lame and sound sows. Before injection
After injection
SEM max
Lame-Placebo
Sound-Meloxicam
Sound-Placebo
Lame-Meloxicam
Lame-Placebo
Sound-Meloxicam
Sound-Placebo
T
P
TxP
Kinematic variables Fore legs Stance time (ms)b Ratio of foot heightc Ratio of stance anglec Ratio of swing angle amplitudec
747.9 0.76 [0.66–0.84] 0.97 [0.95–0.98] 0.89 [0.83–0.93]
735.0 0.76 [0.66–0.84] 0.98 [0.96–0.99] 0.90 [0.85–0.94]
697.4 0.84 [0.74–0.90] 0.97 [0.96–0.98] 0.84 [0.77–0.89]
704.6 0.74 [0.64–0.83] 0.96 [0.94–0.97] 0.87 [0.80–0.91]
696.4 0.79 [0.70–0.86] 0.97 [0.95–0.98] 0.82 [0.75–0.87]
714.7 0.72 [0.61–0.81] 0.97 [0.95–0.98] 0.87 [0.81–0.92]
651.9 0.71 [0.59–0.80] 0.96 [0.94–0.97] 0.90 [0.84–0.94]
647.1 0.69 [0.57–0.78] 0.95 [0.93–0.97] 0.93 [0.88–0.96]
36.0 –
0.44 0.48 0.17 0.27
0.005 0.14 0.09 0.60
0.82 0.36 0.76 0.025
Hind legs Stance time (ms)b Ratio of Foot heightc Ratio of Stance anglec Ratio of Swing angle amplitudec
720.8 0.61 [0.49–0.72] 0.95 [0.92–0.96] 0.80 [0.72–0.86]
703.6 0.63 [0.51–0.73] 0.93 [0.90–0.95] 0.84 [0.78–0.90]
684.7 0.73 [0.61–0.82] 0.97 [0.95–0.98] 0.87 [0.80–0.91]
678.2 0.75 [0.64–0.84] 0.95 [0.92–0.96] 0.78 [0.70–0.84]
702.9 0.64 [0.54–0.74] 0.97 [0.95–0.98] 0.88 [0.82–0.92]
691.5 0.65 [0.53–0.76] 0.94 [0.92–0.96] 0.78 [0.70–0.84]
651.7 0.70 [0.58–0.80] 0.95 [0.92–0.96] 0.81 [0.73–0.87]
651.0 0.81 [0.72–0.88] 0.94 [0.92–0.96] 0.83 [0.75–0.88]
32.4
0.56 0.014 0.19 0.57
0.08 0.50 0.95 0.97
0.94 0.82 0.16 0.054
Force plate variables Fore legs Contralateral ratiod Amplitude of WS e (% BW) Frequency of WS (per min)
0.64 [0.59–0.69] 7.38 25.6
0.67 [0.63–0.72] 7.01 22.3
0.64 [0.59–0.69] 7.37 25.2
0.66 [0.61–0.70] 7.32 23.9
0.66 [0.61–0.70] 7.00 28.2
0.69 [0.64–0.73] 6.6 24.3
0.63 [0.58–0.68] 7.25 25.7
0.67 [0.62–0.72] 7.38 25.6
– 0.41 2.95
0.31 0.69 0.76
0.66 0.07 0.06
0.97 0.41 0.85
Hind legs Contralateral ratio d Amplitude of WSe (% BW) Frequency of WS (per min)
0.65 [0.59–0.71] 6.13 23.2
0.67 [0.61–0.73] 5.84 20.1
0.73 [0.67–0.79] 5.68 22.2
0.71 [0.65–0.77] 5.95 22.3
0.69 [0.63–0.74] 6.23 25.5
0.66 [0.60–0.72] 6.01 21.9
0.74 [0.68–0.79] 5.52 23.4
0.70 [0.64–0.75] 6.04 23.8
0.36 2.72
0.069 0.66 0.75
0.89 0.66 0.04
0.85 0.72 0.97
S. Conte et al. / Livestock Science 180 (2015) 203–208
Lame-Meloxicam
Effecta
a
T: treatments; P: period; T P: interaction. Average value of right and left legs (least square means). c Ratio of lower to higher values between left and right legs (back-transformed least square means [confidence interval]). d Ratio of lower to higher percentage of weight between left and right legs (back-transformed least square means [confidence interval]). e WS: Weight shifting. b
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Table 2 Average kinematics and force plate measurements for fore and hind legs across periods and treatments. Variables (means 7 SD) Kinematics Stride length (m)a Swing time (ms)a Foot height (cm)a Stance angle amplitudea (deg) Swing anglea (deg) Ratio of stance angle amplitudeb Ratio of swing angleb Force plate Percentage of weight (% BW) Percentage of time weight shifting (%) a b
Fore legs
Hind legs
0.85 70.08 441 735 4.0 70.8 17.5 74.1 176 78 0.82 70.12 0.95 70.04
0.83 7 0.08 452 7 39 3.3 7 1.1 12.3 7 3.0 1517 8 0.75 7 0.17 0.95 7 0.04
28.22 70.83 72.49 710.50
21.78 7 0.83 53.75 7 13.27
Average value of right and left legs. Ratio of lower to higher values between left and right legs.
Acknowledgements This work was supported by Agriculture and Agri-Food Canada (RBPI 2056), and Swine Innovation Porc (Project #1004). Authors thank the staff of the swine complex of the Dairy and Swine R&D Centre and of the Prairie Swine Centre for help in the data collection and care of the animals. Authors wish to thank Robert Friendship for his advice on the protocol, Josée Savage, Sébastien Choinière, Benjamin Alègre and Marjolaine St.-Louis for data analyses, and Steve Méthot for statistical advice.
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Flower, F.C., Sedlbauer, M., Carter, E., Von Keyserlingk, M.A.G., Sanderson, D.J., Weary, D.M., 2008. Analgesics improve the gait of lame dairy cattle. J. Dairy Sci. 91, 3010–3014. Fosse, T.K., Spadavecchia, C., Horsberg, T.E., Haga, H.A., Ranheim, B., 2011. Pharmacokinetics and pharmacodynamic effects of meloxicam in piglets subjected to a kaolin inflammation model. J. Vet. Pharmacol. Ther. 34, 367–375. Friton, G.M., Philipp, H., Schneider, T., Kleemann, R., 2003. Investigation on the clinical efficacy and safety of meloxicam (metacams) in the treatment of noninfectious locomotor disorders in pigs. Berl. Munch. Tierarztl. Wochenschr. 116, 421–426. Grégoire, J., Bergeron, R., D’Allaire, S., Meunier-Salaün, M.-C., Devillers, N., 2013. Assessment of lameness in sows using gait, footprints, postural behaviour and foot lesion analysis. Animal 7, 1163–1173. Hadipour, M.M., Hadipourfard, M.B., Vakili, M.B., Shayanpour, N., Azad, F., 2011. Treatment of joint inflammatory diseases in the lame backyard chickens with nsaids. International. J. Anim. Vet. Adv. 3, 73–76. Hansson, M., Lundeheim, N., Nyman, G., Johansson, G., 2011. Effect of local anaesthesia and/or analgesia on pain responses induced by piglet castration. Acta Vet. Scand. 53, 34. Heinonen, M., Peltoniemi, O., Valros, A., 2013. Impact of lameness and claw lesions in sows on welfare, health and production. Livest. Sci. 156, 2–9. Jensen, T.B., Kristensen, H.H., Toft, N., 2012. Quantifying the impact of lameness on welfare and profitability of finisher pigs using expert opinions. Livest. Sci. 149, 209–214. Jones, E., Viñuela-Fernandez, I., Eager, R.A., Delaney, A., Anderson, H., Patel, A., Robertson, D.C., Allchorne, A., Sirinathsinghji, E.C., Milne, E.M., MacIntyre, N., Shaw, D.J., Waran, N.K., Mayhew, J., Fleetwood-Walker, S.M., 2007. Neuropathic changes in equine laminitis pain. Pain 132, 321–331. Keita, A., Pagot, E., Prunier, A., Guidarini, C., 2010. Pre-emptive meloxicam for postoperative analgesia in piglets undergoing surgical castration. Vet. Anaesth. Analg 37, 367–374. Main, D.C.J., Clegg, J., Spatz, A., Green, L.E., 2000. Repeatability of a lameness scoring system for finishing pigs. Vet. Rec. 147, 574–576. Mohling, C.M., Johnson, A.K., Coetzee, J.F., Karriker, L.A., Abell, C.E., Millman, S.T., Stalder, K.J., 2014. Kinematics as objective tools to evaluate lameness phases in multiparous sows. Livest. Sci. 165, 120–128. Mustonen, K., Ala-Kurikka, E., Orro, T., Peltoniemi, O., Raekallio, M., Vainio, O., Heinonen, M., 2011. Oral ketoprofen is effective in the treatment of non-infectious lameness in sows. Vet. J. 190, 55–59. Pairis-Garcia, M.D., Johnson, A.K., Stalder, K.J., Abell, C.A., Karriker, L.A., Coetzee, J.F., Millman, S.T., 2015. Behavioural evaluation of analgesic efficacy for pain mitigation in lame sows. Anim. Welf. 24, 93–99. Pairis-Garcia, M.D., Johnson, A.K., Stalder, K.J., Karriker, L.A., Coetzee, J.F., Millman, S. T., 2014. Measuring the efficacy of flunixin meglumine and meloxicam for lame sows using nociceptive threshold tests. Anim. Welf. 23, 219–229. Pastell, M., Hänninen, L., de Passillé, A.M., Rushen, J., 2010. Measures of weight distribution of dairy cows to detect lameness and the presence of hoof lesions. J. Dairy Sci. 93, 954–960. Peterson, K.D., Keefe, T.J., 2004. Effects of meloxicam on severity of lameness and other clinical signs of osteoarthritis in dogs. J. Am. Vet. Med. Assoc. 225, 1056–1060. Pluym, L.M., Maes, D., Vangeyte, J., Mertens, K., Baert, J., Van Weyenberg, S., Millet, S., Van Nuffel, A., 2013. Development of a system for automatic measurements of force and visual stance variables for objective lameness detection in sows: Sowsis. Biosyst. Eng. 116, 64–74. Ringgenberg, N., Bergeron, R., Devillers, N., 2010. Validation of accelerometers to automatically record sow postures and stepping behaviour. Appl. Anim. Behav. Sci. 128, 37–44. Tapper, K.R., Johnson, A.K., Karriker, L.A., Stalder, K.J., Parsons, R.L., Wang, C., Millman, S.T., 2013. Pressure algometry and thermal sensitivity for assessing pain sensitivity and effects of flunixin meglumine and sodium salicylate in a transient lameness model in sows. Livest. Sci. 157, 245–253. Whay, H.R., Webster, A.J.F., Waterman-Pearson, A.E., 2005. Role of ketoprofen in the modulation of hyperalgesia associated with lameness in dairy cattle. Vet. Rec. 157, 729–733.
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Livestock Science journal homepage: www.elsevier.com/locate/livsci
Use of an analgesic to identify pain-related indicators of lameness in sows S. Conte a, R. Bergeron b, H. Gonyou c, J. Brown c, F.C. Rioja-Lang c, M.L. Connor d, N. Devillers a,n a
Agriculture and Agri-Food Canada, Dairy and Swine R&D Centre, Sherbrooke, QC, Canada, J1M 0C8 University of Guelph, Alfred Campus, Alfred, ON, Canada, K0B 1A0 c Prairie Swine Centre, Saskatoon, SK, Canada, S7H 5N9 d University of Manitoba, Department of Animal Science, Winnipeg, MB, Canada, R3T 2N2 b
art ic l e i nf o
a b s t r a c t
Article history: Received 5 March 2015 Received in revised form 25 August 2015 Accepted 26 August 2015
Lameness in sows may be associated with pain and poor welfare and requires early detection and treatment. The objective of this study was to use the non-steroidal anti-inflammatory drug meloxicam, as a short-term analgesic to identify characteristics of pain-related lameness in sows. A total of 44 pregnant sows were selected from two experimental sites, and used in a 2 2 factorial design. Sows were visually categorized as either non-lame or lame (none with severe lameness), and were either assigned to a placebo (saline) or meloxicam (0.4 mg/kg body weight) treatment. Lameness was assessed using a force plate, kinematic and accelerometer tools on the day before, and after a single intramuscular injection of treatment solution. Data were collected in the same order and at the same time on both days, starting at 7:45, 9:15 and 12:15 for accelerometers, force plate and kinematics, respectively. Before treatment, lame sows made a greater number of steps per min than sound sows (P ¼0.013), and had a tendency to have a lower contralateral ratio of weight applied between the hind legs than sound sows (P¼ 0.062). No other differences were observed between lame and sound sows before treatment. Injection of meloxicam decreased the stepping frequency of the left hind legs (P ¼0.014), increased the ratio of tarsal joint angle amplitude between contralateral hind legs (P¼ 0.05), and tended to increase standing time after feeding in lame sows (P ¼0.09), indicating an improvement of the lameness condition and at least a short-term analgesic effect of meloxicam. Overall, meloxicam effects on lameness variables were limited. The wide variability in the underlying clinical causes, severity and duration of these naturally occurring lameness cases, as well as the timing of lameness assessment in relation to treatment injection may explain the relative lack of treatment effects on kinematics and force plate variables. More research is needed to identify pathology-specific indicators of pain-related lameness. Crown Copyright & 2015 Published by Elsevier B.V. All rights reserved.
Keywords: Accelerometers Force plate Kinematics Lameness Meloxicam Sow
1. Introduction Early detection of lameness is important to provide prompt treatment and hence improve welfare (Flower et al., 2005). Lameness can have multiple origins in sows: osteochondrosis, arthritis, osteoarthritis, osteomyelitis, abscesses, bursitis, and various claw lesions and leg injuries (Heinonen et al., 2013). In finisher pigs, experts have associated causes of lameness with various degrees of pain, and ranked fractures, osteochondrosis dissecans and infectious arthritis as most painful (Jensen et al., 2012). Research to identify and validate pain indicators in sows is very limited despite the necessity to recognise pain-related lameness n
Corresponding author. Fax: þ 1 819 564 5507. E-mail address: [email protected] (N. Devillers).
http://dx.doi.org/10.1016/j.livsci.2015.08.009 1871-1413/Crown Copyright & 2015 Published by Elsevier B.V. All rights reserved.
for welfare reasons. In cows, changes in behaviour or gait following the administration of an analgesic were difficult to identify, while differences in weight distribution on a force plate were observed (Chapinal et al., 2010a, 2010b; Flower et al., 2008; Whay et al., 2005). Whay et al. (2005) hypothesised that behavioural expression of pain is likely to be very subtle and suggested that more work is required to determine behaviours that would be indicators of pain in lame animals. The use of automated methods such as accelerometers to measure stepping, kinematics or force plate (Conte et al., 2014; Grégoire et al., 2013) may help identify subtle changes in the gait and postural behaviour after alleviating pain compared to visual observation. In Europe and Canada, a nonsteroidal anti-inflammatory drug (NSAID) called meloxicam, sold s under the product name Metacam , is licensed for the treatment of lameness in pigs at a dose of 0.4 mg/kg i.m. In dogs and chickens, meloxicam is considered as the drug of choice to treat
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osteoarthritis and joint inflammatory diseases (Cross et al., 1997; Hadipour et al., 2011; Peterson and Keefe, 2004). To our knowledge, very few published studies have assessed the effect of meloxicam on swine lameness. Friton et al. (2003) found a reduction in lameness days after the injection of meloxicam in pigs (gilts, sows and finishers), using a scoring system based on the observation of weight-bearing on limbs. More recently, Pairis-Garcia et al. (2014) demonstrated the effectiveness of meloxicam at reducing pain in sows with induced lameness, using nociceptive threshold tests. The aim of the present project is to use meloxicam as a shortterm analgesic to identify, using quantitative methods (force plate, kinematics and accelerometers), characteristics of pain-related lameness in sows that are mildly and moderately lame.
2. Materials and methods Animals were cared for according to the Canadian Council on Animal Care guidelines (Canadian Council on Animal Care, 2009) and a recommended code of practise (Agriculture and Agri-Food Canada, 1993) and the experimental protocol was approved by the institutional animal care committee of the Dairy and Swine R&D Centre (Sherbrooke, Quebec, Canada) and the University of Saskatchewan's Animal Research Ethics Board (Saskatoon, Saskatchewan, Canada). 2.1. Animals and treatments A total of 44 primiparous (n ¼5) and multiparous (n ¼39) Landrace Yorkshire sows (267734 kg BW) were selected from the Dairy and Swine R&D Centre (DSRDC, n ¼16; Sherbrooke, Quebec, Canada) and the Prairie Swine Centre Inc. (PSC, n ¼28; Saskatoon, Saskatchewan, Canada) and used in a 2 2 factorial design. Sows were housed in individual pens of 2.97 m2 (DSRDC) or in groups of approximately 30 animals with walk-in/lock-in feeding stalls (PSC), both with partially slatted concrete floors. Once per week (n ¼11), four sows (from the same group at PSC) between 29 and 76 days into gestation were selected according to the following criteria: no obvious leg injuries or severe lameness, and not medicated with non-steroidal anti-inflammatory drugs, glucocorticoids or antibiotics within the previous 14 days before the experiment (Friton et al., 2003; Mustonen et al., 2011). Using a visual gait scoring system adapted from Main et al. (2000), sows were individually scored, while walking in a corridor on plain concrete floor, on a scale from 0 to 4 (0: normal gait and even strides; 1: abnormal gait, stiffness, but lameness not easily identified; 2: lameness detected, shortened strides, sow puts less weight or avoids putting weight on one leg; 3: sow does not bear weight on one leg; 4: non-ambulatory) and then categorized as sound (score 0, n ¼21) or lame (score 1, n ¼5 or score 2, n¼ 18). Sows scored 3 or 4 were not selected because the study aimed at validating pain-related criteria for early identification of lameness. Therefore, sows that were obviously in pain and non-ambulatory were excluded. Two lame and two sound sows were selected each week. The day after visual scoring, gait score was visually confirmed and lameness was assessed using the force plate, kinematics and accelerometers tools, as previously described (Conte et al., 2014; Grégoire et al., 2013; Ringgenberg et al., 2010). Then, sows were put back in their home pen. On the following day, the two lame and two sound sows were assigned randomly to either meloxicam s treatment (Metacam , Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany) or a placebo treatment (saline solution), to which the experimenter was blind and lameness was assessed again using the same methods in the same order. The
dose of meloxicam of 0.4 mg/kg body weight recommended by the manufacturer (20 mg/ml, 0.02 ml/kg) was administered as a single intramuscular injection in the neck region at 7:15. Stepping behaviour, weight distribution and gait were measured on each sow within an 8 h-period after the i.m. injection. In sows, the time to reach the maximum plasma concentration (Tmax) after per os administration of 0.5 mg/kg of meloxicam was 2.4 h, and half-life (T1/2) was 6.83 h, while the i.v. half-life was 6.15 h (Pairis-Garcia et al., 2014a). When 0.6 mg/kg were administered i.m. to piglets, Tmax ranged from 0.4 to 1.8 h (Fosse et al., 2011). Therefore, measurements in the present experiment were likely performed around the time at which the drug was the most effective. Data were collected in the same order and at the same time on both days (day before and day of treatment), starting at 7:45, 9:15 and 12:15 for accelerometers, force plate and kinematics, respectively. All measurements were recorded by the same experimenter. The number of sows was initially balanced between treatments within experimental farms but one sow was moved a posteriori from the Sound-Meloxicam to the Lame-Meloxicam group because her lameness score increased between the day of selection and the day before treatment. Therefore, numbers of sows per treatment were 12 for Lame-Meloxicam, 11 for Lame-Placebo, 10 for Sound-Meloxicam and 11 for Sound-Placebo. 2.2. Measurements and calculations 2.2.1. Accelerometers Acceleration recordings were made for 1 h following the start of feeding to determine the number of steps per min while the sow stood, following a procedure previously used (Conte et al., 2014). Sows were fed in a trough within their individual pen (DSRDC) or in a feeding stall (PSC) where they were kept for 1 h. s One accelerometer (Hobo Pendant G Data Logger, Onset Computer Corporation, Pocasset, MA, USA), safely protected inside a Velcros-pocket and a VetrapTM 3MTM covering, was placed on each hind leg. The device recorded the acceleration on the x-axis (10 data per second), for 1 h. A step was considered true if the xaxis acceleration was o0.6 g or 4 1.4 g (Ringgenberg et al., 2010), while the animal was in a standing position. The latency to lie down after feed delivery, corresponding to acceleration on the xaxis o0.59 g, was also determined. Data from recordings were s read using the Hoboware Pro software (Onset Computer Corporation, Pocasset, MA, USA). 2.2.2. Force plate The force plate (Pacific Industrial Scale Co. Ltd., Richmond, BC, Canada) consisted of four individual stainless steel platforms (front: 101.6 30.5 cm2, rear: 111.8 30.5 cm2), each resting on four single-ended beam load cells. A feeder was included on the front gate to draw the sow's attention towards a standardized direction. The total weight and the weight placed on each platform (14 data per second) were recorded and saved using the Pacweight Animal Weight custom software (Pacific Industrial Scale Co. Ltd.). Two cameras were used to record the position of the sow's legs using the Omnicast video surveillance system (Genetec Inc.©, version 4.6, 2001–2012, Montreal, Quebec, Canada), which was synchronized with the Pacweight Animal Weight custom software. Sows were measured for a period of 15 min, but only periods when the sow stood with her head in the feeder and her legs in the correct platform were kept and any body weight per reading higher or lower than 5% of the average body weight of the sow was eliminated as previously described (Conte et al., 2014). For each leg, the average percentage of weight (% BW) was calculated. The average ratio of lower to higher weight applied by contralateral legs was calculated separately for fore and hind legs (contralateral ratio). Weight shifting was evaluated according to
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the same method previously described (Conte et al., 2014) and frequency of weight shifting per min (WS), percentage of time WS (% of time WS) and amplitude of WS (% BW) were calculated. 2.2.3. Kinematics Each sow was equipped with fifteen reflective markers placed in standardised locations on the body and was video recorded while walking along a corridor 7.3 m long and 1.1 m wide (plain concrete floor type). The detailed procedure has previously been described by Conte et al. (2014). Each side of the sow was recorded s separately with a DFK22AUC03 camera (The Imaging Source Europe GmbH, Bremen, Germany) with lens (Pentax CCTV C418DX, 4.8 mm, 1: 1.8, Pentax Ricoh Imaging Americas Corporation, Denver, CO, USA) using the IC Imaging Capture 2.2 software (The Imaging Source Europe GmbH, Bremen, Germany). Gait chars acteristics were analysed using the motion analysis MoviAS Pro software (NAC Image Technology, Simi Valley, USA). The data measured for each leg were stance time, swing time, foot height, stride length, average angle and amplitude of joints angle for the carpal joint for fore leg, and the tarsal joint for hind leg during the swing and stance periods. The average value from 3 individual steps was used in the analysis. 2.3. Statistical analyses The frequency of stepping behaviour for right leg and left leg separately, the average frequency of stepping (between right and left legs), and the latency to lie down after feeding were analysed using the Kruskal–Wallis test for period before the injection, with state (lame vs. sound) and solution (meloxicam vs. placebo) in the model, and then with the four treatments in the model. The delta values (difference between the measure after and before the injection) for the above variables were calculated and analysed using the Kruskal–Wallis test with the four treatments in the model. Data are presented in the text as median with lower–upper quartiles between brackets. Correlations between left and right legs measures from the force plate and the kinematics were done. Variables with a significant positive correlation between right and left legs were averaged for fore and hind legs separately (frequency of WS, % of time WS, amplitude of WS, stride length, swing and stance time). For variables with negative or no correlation between right and left legs, a ratio (lowest value/highest from the right and left legs) was calculated for front and hind legs separately (foot height, carpal and tarsal angle during swing and stance phase, carpal and tarsal angle amplitude during swing and stance phase) in order to measure asymmetry. The MIXED procedure was used on measures that were averaged between right and left legs, with the state (lame vs. sound) and the solution (meloxicam vs. placebo) in the model. The GLIMMIX procedure with a beta distribution and a logit link function was used on ratios with the state and the solution in the model. The analyses were firstly done separately for measures before and after injection, then using a model with the period (before vs. after injection) as repeated measures and the four treatments (Lame-Meloxicam, Lame-Placebo, Sound-Meloxicam, Sound-Placebo) in the model. Data from the MIXED procedure are presented as least square mean 7maximum SEM. Data from the GLIMMIX procedure are expressed as back transformed least square mean with the confidence interval between square brackets.
3. Results and discussion The present study partly confirms previous results on the usefulness of some variables for the differentiation between lame
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and sound sows. Before treatment, lame sows made a greater number of steps per min than sound sows (6.5 (4.3–7.4) vs. 3.3 (2.2–6.4), respectively, P ¼0.013). This difference existed for both right (5.3 (4.3–8.3) vs. 3.2 (2.3–5.4), respectively; P ¼0.018) and left hind legs (6.5 (3.3–8.4) vs. 3.7 (2.4–7.1), respectively; P¼ 0.07) and are in accordance with Grégoire et al. (2013). Lame sows also had a tendency to have a lower contralateral ratio of weight applied on the hind legs than sound sows (0.66 [0.61–0.71] vs. 0.72 [0.68–0.76], respectively; P ¼0.062), as already shown by Conte et al. (2014). However, no additional differences were observed between lame and sound sows before treatment for force plate and kinematics measurements (data not shown; P4 0.10), as expected from the same previous studies. In contrast to what has been previously observed by Grégoire et al. (2013), there was no significant difference between lame and sound sows for the latency to lie down following feeding (46.1 min (28.3–60.0) vs. 54.8 min (36.7–60.0), respectively; P¼ 0.16). Force plate measurements did not show significant differences in weight shifting values contrary to the results from Conte et al. (2014). Finally, there were no variations in gait parameters such as a shorter stride length or a longer stance time in lame sows (Grégoire et al., 2013; Mohling et al., 2014). These few differences between lame and sound sows before any treatment unfortunately lower the potential of the present study to detect an effect of meloxicam. It should be noted that lame sows in the present study presented lower lameness scores than those of Grégoire et al. (2013) and Conte et al. (2014), because the focus was on lameness cases that were not obviously painful. In line with the lack of differences in gait and weight distribution between lame and sound sows, our study did not succeed in demonstrating a clear and significant short-term effect of the injection of meloxicam on most measured variables. Nevertheless, injection of meloxicam significantly decreased the stepping frequency of the left hind leg as shown by the negative delta value between after and before the injection for Lame-Meloxicam sows (Fig. 1). This negative delta value indicates an improvement of Lame-Meloxicam sows' condition. It also suggests that most of these sows probably had a painful left hind leg. Indeed, considering lame and sound sows separately, lame sows receiving the meloxicam showed a significant improvement in the stepping frequency compared to sows receiving a placebo, whose condition deteriorated (P¼ 0.031). In contrast, there was no difference for sound sows (P¼ 0.79). This effect, only observed on left hind legs, highlights the fact that sow distribution between treatments in terms of pathology underlying lameness or which leg was painful was not balanced. This also confirms the challenge of studying lameness in naturally lame sows without being able to diagnose the cause of lameness and the legs affected. Despite the lack of differences before treatment, there was a tendency for a difference between the four treatments in the delta value for the latency to lie down (Lame-Meloxicam: 3.7 (0–11.4), Lame-Placebo: 0 ( 15.8 to 2.4), Sound-Meloxicam: 0 ( 6.1 to 0.7), Sound-Placebo: 0 ( 21.8 to 0) min; P ¼0.09), indicating that lame sows receiving meloxicam were standing for a longer time following feeding after the injection compared to the day before. Finally, a significant interaction between treatments and period was found for the ratio of angle amplitudes of carpal and tarsal joints during swing time (Table 1). The ratio of angle amplitude between contralateral legs of lame sows receiving meloxicam was reduced in fore legs after injection, while it was increased for hind legs. An increase in the ratio would mean a better symmetry of the movement between contralateral legs, and potentially an improvement of the lameness condition. This improvement would support the fact that most lame sows were affected at hind legs and that meloxicam had an effect on alleviating pain related to walking. Beyond these few differences, there were no significant
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Fig. 1. Effect of the injection of meloxicam (Mlx) or a placebo (Pcb) on the stepping frequency of lame and sound sows (boxplot (min, 1st quartile, median, 3rd quartile, max) for delta values calculated as after minus before the injection).
interactive effects of treatments and period, which would indicate an effect of meloxicam, on variables measured with the force plate for the fore or hind legs (P 40.10, Table 2) and most of the variables measured with kinematics for the fore or hind legs (P 40.10, Table 2). Pairis-Garcia et al. (2014) showed a significant improvement in pain sensitivity to pressure from 7.5 h after oral administration of meloxicam (1 mg/kg), which corresponds to T1/2, but not at Tmax (i.e. 2 h after administration) in sows with an induced lameness. On the other hand, they saw a significant improvement in pain sensitivity to focussed radiant heat stimulation at Tmax but not during the following 24 h. Pairis-Garcia et al. (2015) also showed a reduction in lying posture frequencies 24 h after meloxicam treatment. Friton et al. (2003) observed an improvement in clinical lameness score at rest and while walking 24 h post-injection (0.4 mg/kg i.m.). In the present study, the main effect, observed as a decrease in the stepping frequency and a longer period standing, occurred at a time when the drug concentration had likely reached its maximum value. Previous studies on the use of meloxicam to alleviate pain following castration in piglets showed its effectiveness in reducing physiological and behavioural indicators of pain in the first hour following the procedure (Hansson et al., 2011; Keita et al., 2010). According to our results, stepping frequency could be related to pain sensitivity and, in accordance with previous studies (Conte et al., 2014; Grégoire et al., 2013; Pluym et al., 2013), would make a promising indicator of pain-related lameness. However, the present study did not succeed in determining specific pain-related indicators of naturally occurring lameness using the force plate and the kinematics methodologies that would help in identifying the affected leg. Lameness is a multifactorial problem and the wide variations observed between sows in their gait, weight distribution and postural behaviour could depend on the underlying clinical cause, its severity and the number of legs affected. Because it is very difficult to make an accurate diagnosis on live animals, the experimenter was not able to know the clinical cause of lameness and its severity. It should also be noted that sows were not monitored over a long period of time prior to the start of the experiment. Therefore, it was not possible to determine whether selected sows were suffering from acute or chronic pain. In horses suffering from laminitis, persistent pain may lead to a decrease in effectiveness of analgesic protocols (Jones et al., 2007). In addition, it could be hypothesised that sows suffering from a chronic condition may have habituated to their antalgic gait, and may have required more time to resume their normal posture and gait following analgesia. Although sows
served as their own control, selection of sows based only on a global visual score possibly introduced large variations in the cause, severity and duration of lameness, and in the number of legs affected, which may have masked the effect of meloxicam. To solve this problem, the use of an induced lameness model allowing a better standardisation of the type of lameness would help to assess the effectiveness of analgesics as demonstrated by PairisGarcia et al. (2014) and Tapper et al. (2013). However, the validity of such model to simulate naturally occurring lameness can still be questioned, especially for chronic pathologies such as arthritis or osteochondrosis. The ability to select animals affected by the same pathology would also improve standardisation and homogeneity of symptoms and results as observed in cows (Pastell et al., 2010). The effectiveness of meloxicam to relieve lameness pain in the short-term is still questioned in sows as its analgesic properties are related to its anti-inflammatory action and may take several hours to be noticeable. In the study by Friton et al. (2003), lameness assessment in sows was not done in the period of time immediately following i.m. administration of 0.4 mk/kg of meloxicam, but only 24 h after. Drugs that more specifically target neuropathic pain, such as gabapentin, could be useful to specifically identify characteristics of pain-related lameness (Coetzee et al., 2014). Finally, it is possible that the recommended dose used in the present study was not sufficient for the drug to reach its maximum pain-relieving effect. In their study on nociceptive thresholds following administration of meloxicam, (Pairis-Garcia et al., 2014), used a dose of 1 mg/kg, but it was administered orally. More research on the pharmacokinetics of meloxicam in sows following i.m. administration would be necessary to extrapolate from their results.
4. Conclusion Meloxicam i.m. injection to lame sows resulted in a decrease in the stepping frequency measured with accelerometers, and a better symmetry of hind legs movement as measured by the ratio of angle amplitude between contralateral hind legs. All other variables were unaffected by treatment. Timing of lameness measurement with force plates and kinematics in relation to meloxicam treatment may explain its lack of effect. Further research is still needed to identify specific pain-related indicators of lameness in naturally lame sows and more specifically on the development of tools or indicators to identify pathologies or affected legs on live animals.
Table 1 Effect of Meloxicam or placebo injections on kinematics and force plate variables measured on lame and sound sows. Before injection
After injection
SEM max
Lame-Placebo
Sound-Meloxicam
Sound-Placebo
Lame-Meloxicam
Lame-Placebo
Sound-Meloxicam
Sound-Placebo
T
P
TxP
Kinematic variables Fore legs Stance time (ms)b Ratio of foot heightc Ratio of stance anglec Ratio of swing angle amplitudec
747.9 0.76 [0.66–0.84] 0.97 [0.95–0.98] 0.89 [0.83–0.93]
735.0 0.76 [0.66–0.84] 0.98 [0.96–0.99] 0.90 [0.85–0.94]
697.4 0.84 [0.74–0.90] 0.97 [0.96–0.98] 0.84 [0.77–0.89]
704.6 0.74 [0.64–0.83] 0.96 [0.94–0.97] 0.87 [0.80–0.91]
696.4 0.79 [0.70–0.86] 0.97 [0.95–0.98] 0.82 [0.75–0.87]
714.7 0.72 [0.61–0.81] 0.97 [0.95–0.98] 0.87 [0.81–0.92]
651.9 0.71 [0.59–0.80] 0.96 [0.94–0.97] 0.90 [0.84–0.94]
647.1 0.69 [0.57–0.78] 0.95 [0.93–0.97] 0.93 [0.88–0.96]
36.0 –
0.44 0.48 0.17 0.27
0.005 0.14 0.09 0.60
0.82 0.36 0.76 0.025
Hind legs Stance time (ms)b Ratio of Foot heightc Ratio of Stance anglec Ratio of Swing angle amplitudec
720.8 0.61 [0.49–0.72] 0.95 [0.92–0.96] 0.80 [0.72–0.86]
703.6 0.63 [0.51–0.73] 0.93 [0.90–0.95] 0.84 [0.78–0.90]
684.7 0.73 [0.61–0.82] 0.97 [0.95–0.98] 0.87 [0.80–0.91]
678.2 0.75 [0.64–0.84] 0.95 [0.92–0.96] 0.78 [0.70–0.84]
702.9 0.64 [0.54–0.74] 0.97 [0.95–0.98] 0.88 [0.82–0.92]
691.5 0.65 [0.53–0.76] 0.94 [0.92–0.96] 0.78 [0.70–0.84]
651.7 0.70 [0.58–0.80] 0.95 [0.92–0.96] 0.81 [0.73–0.87]
651.0 0.81 [0.72–0.88] 0.94 [0.92–0.96] 0.83 [0.75–0.88]
32.4
0.56 0.014 0.19 0.57
0.08 0.50 0.95 0.97
0.94 0.82 0.16 0.054
Force plate variables Fore legs Contralateral ratiod Amplitude of WS e (% BW) Frequency of WS (per min)
0.64 [0.59–0.69] 7.38 25.6
0.67 [0.63–0.72] 7.01 22.3
0.64 [0.59–0.69] 7.37 25.2
0.66 [0.61–0.70] 7.32 23.9
0.66 [0.61–0.70] 7.00 28.2
0.69 [0.64–0.73] 6.6 24.3
0.63 [0.58–0.68] 7.25 25.7
0.67 [0.62–0.72] 7.38 25.6
– 0.41 2.95
0.31 0.69 0.76
0.66 0.07 0.06
0.97 0.41 0.85
Hind legs Contralateral ratio d Amplitude of WSe (% BW) Frequency of WS (per min)
0.65 [0.59–0.71] 6.13 23.2
0.67 [0.61–0.73] 5.84 20.1
0.73 [0.67–0.79] 5.68 22.2
0.71 [0.65–0.77] 5.95 22.3
0.69 [0.63–0.74] 6.23 25.5
0.66 [0.60–0.72] 6.01 21.9
0.74 [0.68–0.79] 5.52 23.4
0.70 [0.64–0.75] 6.04 23.8
0.36 2.72
0.069 0.66 0.75
0.89 0.66 0.04
0.85 0.72 0.97
S. Conte et al. / Livestock Science 180 (2015) 203–208
Lame-Meloxicam
Effecta
a
T: treatments; P: period; T P: interaction. Average value of right and left legs (least square means). c Ratio of lower to higher values between left and right legs (back-transformed least square means [confidence interval]). d Ratio of lower to higher percentage of weight between left and right legs (back-transformed least square means [confidence interval]). e WS: Weight shifting. b
207
208
S. Conte et al. / Livestock Science 180 (2015) 203–208
Table 2 Average kinematics and force plate measurements for fore and hind legs across periods and treatments. Variables (means 7 SD) Kinematics Stride length (m)a Swing time (ms)a Foot height (cm)a Stance angle amplitudea (deg) Swing anglea (deg) Ratio of stance angle amplitudeb Ratio of swing angleb Force plate Percentage of weight (% BW) Percentage of time weight shifting (%) a b
Fore legs
Hind legs
0.85 70.08 441 735 4.0 70.8 17.5 74.1 176 78 0.82 70.12 0.95 70.04
0.83 7 0.08 452 7 39 3.3 7 1.1 12.3 7 3.0 1517 8 0.75 7 0.17 0.95 7 0.04
28.22 70.83 72.49 710.50
21.78 7 0.83 53.75 7 13.27
Average value of right and left legs. Ratio of lower to higher values between left and right legs.
Acknowledgements This work was supported by Agriculture and Agri-Food Canada (RBPI 2056), and Swine Innovation Porc (Project #1004). Authors thank the staff of the swine complex of the Dairy and Swine R&D Centre and of the Prairie Swine Centre for help in the data collection and care of the animals. Authors wish to thank Robert Friendship for his advice on the protocol, Josée Savage, Sébastien Choinière, Benjamin Alègre and Marjolaine St.-Louis for data analyses, and Steve Méthot for statistical advice.
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