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Subjects:
Agriculture, Dairy & Animal Science
The main conditions and diseases considered painful in dairy cows are mastitis, lameness, calving (including dystocia and caesarean section) and metritis. The cattle literature reports that deviation from normal daily activity patterns (both increased and/or reduced daily lying time) can be indicative of painful conditions and diseases in cows. This narrative review discusses on how pain due to several health conditions in dairy cows modifies its activity pattern and explores if non-steroidal anti-inflammatory drugs (NSAIDs) are capable of restoring it. Divergent outcomes may differ depending upon the painful cause, the severity and the moment, and consequently its interpretation should be properly explained. For instance, cows with clinical mastitis reduced their time lying and increased the number of lying bouts and stepping due to pain caused by the swollen udder when cows are lying. However, lame cows show longer lying times, with a lower number of lying bouts and longer and more variable lying bouts duration, as compared to non-lame cows. When the relationship between painful disorders and daily activity patterns is studied, factors such as parity, bedding type and severity of disease are important factors to take into consideration. The potential benefits of the NSAIDs treatment in painful health disorders depend upon the type of drug administered, its dosage and administration mode, and the time of administration relative to the painful health disorder.
- cow
- pain
- activity
- lying time
- welfare
1. The Sensory and Emotional Experience of Pain
It is generally accepted that animal welfare comprises physical and mental health [10] and includes several aspects such as absence of thirst, hunger, discomfort, disease, pain, injuries and stress, as well as the possibility to express normal behaviours [11]. As a consequence, one of the essential components of good welfare is the recognition and control of pain.
Humans and vertebrates share similar neuroanatomical structures associated with pain perception, namely, nociceptors, nociceptive pathways and processing areas in the central nervous system (CNS) [12,13]. As a consequence, it is well established that farm animals are capable of experiencing pain.
Pain is defined by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage [14]. By this definition, pain is a subjective experience which requires the activity of structures in the brain to be perceived. This is in contrast to nociception, which is defined as the encoding and processing of noxious stimuli in the nervous system. Pain has a fundamentally important protective role, alerting us to threats and providing an impetus for the preservation of the integrity of the body. However, in the context of veterinary treatment of illness or injury, pain may become an unwanted consequence that is generally not useful and compromises the welfare of animals. Pain can be developed following tissue damage, inflammation and nerve injury [15]. Pain is usually transitory, lasting only until the noxious stimulus is removed or the underlying damage or pathology has healed (acute pain). However, chronic pain may persist for months and can be even more detrimental to animal welfare [16]. Chronic pain is characterized by hypersensitivity to potentially painful stimulation and is clinically manifested as spontaneous pain (pain in the absence of any stimulation), as well as hyperalgesia (an exaggerated response to a noxious stimulus) and allodynia (the presence of a pain response to a non-noxious stimulus, such as a gentle touch) [17].
Nociceptive pain may also be classified according to the site of origin (a terminology that will be used in the present review). Visceral pain results from the activation of nociceptors of the thoracic, pelvic or abdominal viscera. Visceral pain is diffuse, difficult to localize and often referred to a distant, usually superficial, structure. Superficial somatic pain is initiated by activation of nociceptors in the skin or other superficial tissue, and is sharp, well-defined and clearly located [18,19].
The pain experienced by cattle may be the result of management procedures such as castration, dehorning and tail docking, or a variety of conditions and diseases considered painful. According to different surveys of farmers and veterinarians [20,21,22,23], the main conditions and diseases considered painful in dairy cows and reviewed in the present work are mastitis, lameness, calving (including dystocia and caesarean section) and metritis. Many of these conditions occurred on the farm without the use of anaesthetics and/or analgesics for pain management [1]. Veterinarians are expected to be able to diagnose, score and treat pain in cattle. A large variability in pain scores for individual diseases and pain conditions in cows, as well as in analgesic treatment practices in cows, have been documented [21,24]. One reason for the inconsistency in pain recognition and thus pain relief in cattle is the inadequate ability to identify and assess pain [25]. In addition, economic and legislative considerations may be significant factors, too [26].
2. Pain Identification and Assessment in Cows
There are at least two reasons that explain why assessing pain in ruminants is particularly challenging. Firstly, as pain is a subjective personal experience, it is very difficult to objectively measure it scientifically and validate it in animals. Secondly, from an evolutionarily perspective, cattle are considered a prey species, and are inclined to avoid showing pain, even when exposed to harmful stimuli. This stoicism makes identification of pain, and therefore disease, a challenging task [27,28].
Pain indicators should be reliable (repeatable), valid and sensitive. Reliability is tested to ensure that the indicator is repeatable between (inter) and within (intra) observers and is not affected by observer bias or observer subjectivity. Validity ensures that the indicator is measuring pain and not related to any other state such as fear, anxiety or general sickness behaviour. A pain indicator should be sensitive, meaning that it allows the detection of different levels of pain and that it increases linearly with the severity of pain [29]. In addition, indicators for on-farm use should be readily applied, inexpensive, non-invasive and provide immediate (not retrospective) information [30].
Ideally, pain indicators should be validated by a “gold standard”. In humans, the self-reporting of pain has been the most commonly used method of pain assessment and validation both in clinical practice and research [31,32]. Perceived pain in animals cannot be directly measured or based upon other measures; it can only be inferred [32]. Since validation is based upon the measurement of an indicator against a “gold standard”, pain indicators must be thoroughly evaluated using experimental studies. The majority of studies used several measures simultaneously, with different experimental approaches, to evaluate the potential value of these measures as indicators of pain [32]. Pain assessment in animals has tended to use four approaches: measures of general indices, physiological indicators, behavioural indicators [28] and, recently, facial expressions [33]. Some studies integrate those measures into a graded scale in order to fully assess the impact of a painful condition or event on the individual (e.g., [7]). Pain assessment based on behaviour has received increasing attention and is the most commonly used parameter to assess pain in farm animals [34]. Three types of behaviours, useful for pain evaluation in farm animals, have been proposed [7,28]: (1) pain-specific behaviours; (2) avoidance-of-pain behaviours; and (3) a change in certain behaviours that the animals are very motivated to perform.
Pain-specific behaviours encompass a promising method of assessing pain in farm animals (e.g., [30]). This approach has been used extensively in rodents to assess pain in order to provide the best possible treatment and refine painful techniques [35]. For instance, decreased burrowing behaviour and voluntary wheel running, weight bearing/gait, abnormal postures, paw flinches and ultrasonic vocalizations have been systematically observed in multiple rat models of chronic pain [36]. However, pain-specific behaviours are usually obtained by direct and continuous observations by trained observers (e.g., [7,29]), thus making it time-consuming.
Avoidance-of-pain behaviours assess the reaction of animals upon being manipulated and is a commonly used method to assess pain. These indicators are considered valid and reliable as long as the reaction is scored in a standardized way [37]. Pain sensitivity has been quantified using mechanical (e.g., [38]) or thermal stimulation of a hind leg or the udder (e.g., [39]), mainly to assess pain in cows suffering from mastitis. These methods measure the nociceptive threshold, defined as the minimum stimulus necessary to elicit a pain response. When a stimulus is applied to a painful site, a cow responds with avoidance behaviour such as kicking, leg lifting or tail flicking [40]. Lower nociceptive threshold values indicate that there is increased pain.
A change in certain normal behaviours, such as daily activity patterns, including lying behaviour, has been used extensively in the cattle literature to assess pain caused by several conditions. However, up to now, behavioural activity patterns have not been properly interpreted as a pain indicator in cows. Several electronic data loggers are widely available and can be used to measure lying behaviour accurately, including the total time spent lying down, the number of lying bouts and the duration of each bout for individual cows [41]. The automatic recording of behavioural activity (lying, standing and walking) can be achieved using a variety of sensor systems; for example, mercury tilt switches, three-dimensional accelerometers embedded sensor technology and automatic local position systems [42,43].
Daily activity patterns indicative of pain in cows have been investigated in experimental studies by (a) animals as their own control: observing animals before, during and after a painful process or procedure; (b) comparing animals thought to be in pain to the controls (pain-free animals); (c) observing animals thought to be in pain and receiving effective analgesia, as compared to a placebo; and (d) observing whether indicators of pain increase with the severity of pain. Ideally, a combination of these methods would be used to test the validity of behavioural pain indicators [30].
The main behavioural indicator of activity patterns used in cows is the time spent lying down. Other related behavioural indicators of activity patterns used are the frequency of lying bouts (i.e., a transition from standing to lying), the duration of individual bouts and activity or number of steps. Healthy lactating cows lay down 11.0 ± 2.1 h/d in 9 ± 3 bouts/day, with a bout duration of 88 ± 30 min/bout. These values ranged from 9.5 to 12.9 h/d, 7 to 10 bouts/d and 65 to 112 min/bout across farm means [44]. However, lying behaviour varies considerably among dairy systems, with the shortest duration often in pasture systems and the longest usually in tie-stalls (see [9] for further revision).
Lying is a behavioural need for dairy cattle. Lying is considered to be a higher priority than eating and social contact when opportunities to perform these behaviours are restricted [45]. As a consequence, lying behaviour has been identified as an element that can be used to measure a cow’s welfare status [45,46,47]. Lying behaviour has been identified as a sensitive measure of animal comfort (e.g., [48]) and to assess pain caused by several conditions in cows (e.g., [49]). Deviation from normal lying behaviour (both increase or reduction) can be indicative of pain in cows. Longer lying times (within a normal range) are generally indicative of increased welfare [9]. However, resting for a long time with few lying bouts can also indicate illness. Sickness behaviour is a well-organized adaptive response to enhance disease resistance and facilitate recovery from disease [50]. Sickness behaviour includes changes in behaviour and physiology. In fact, tissue injury and infection unleash the signals necessary for immune activation. Inflammatory mediators released during immune activation are initiated by a group of chemical mediators known as cytokines [51]. Interleukins are a particularly important group of compounds within cytokines and they mediate the acute-phase response by initiating fever, synthesis of acute-phase proteins and the immune response originating in lymphoid tissue, among others [51]. Beside this, they act on the brain (hypothalamus), which initiates anti-inflammatory mechanisms and some of the main behavioural effects involved in sickness behaviour. Sickness behaviour can include lethargy, apathy, somnolence, fever, loss of appetite and thirst, reduced social interaction and a decrease in general physical activity, among other symptoms. Lying is often increased in ill animals [50,52], where reduced activity is considered beneficial for energy conservation and maintenance of the febrile response [53].
Overall, in order to properly understand how a painful condition can affect lying behaviour in cows, different aspects have to be considered. Firstly, the origin, location, intensity and source of pain have to be identified. Secondly, irrespective of pain, it is necessary to identify if the cow shows some or several symptoms associated with sickness behaviour.
Daily activity patterns are affected by different factors others than pain. Studies assessing pain in cows should standardize other factors affecting daily activity patterns or at least consider them as influencing factors. Daily activity patterns can be influenced by individual, environmental, housing system and management factors. The main individual factors described are parity [54], social ranking [55], days in milk (DIM) [56] and milk yield [48]. The main environmental factors described are seasonal changes [57,58], including heat stress [59]. The main housing-system factors described are dairy systems [60,61,62,63], stall dimensions [64], stall features [65,66], stall surface [67] and bedding material [68]. The main management factors described are stocking density [69,70,71], grouping strategies [72], feeding management [73] and time spent away from the pen for milking [65]. In summary, other factors are known to have an important effect on daily activity patterns (especially lying behaviour). Clearly, these factors have to be taken into consideration when an experimental study assessing pain through daily activity patterns is done and caution is required in extrapolating findings to other conditions.
3. Pain Management in Dairy Cows
Pain relief is based on treating inflammation and other systemic effects that commonly accompany inflammation and slow any further tissue damage. The use of corticosteroids may not be appropriate because of their immunosuppressive and metabolic side effects [74,75]. Numerous NSAIDs are available and licensed for use in farm animals, demonstrating their safety and efficacy. Over the last decade, there has been an increase in their use, probably because there is increasing evidence to support the benefits in painful diseases such as lameness, mastitis and metritis [26]. NSAIDs are commonly used in animals to reduce inflammation (anti-inflammatory), reduce pain (analgesic) and decrease overall body temperature (antipyretic). Incorporating NSAID therapy into treatment protocols for a variety of painful conditions should improve the welfare of animals and, consequently, decrease the related economic losses [40,76]. When a NSAID is administered prior to a specific painful condition or disease (instead of administering NSAIDs during or after the painful moment), animals returned to a normal physiologic state more quickly [77]. NSAIDs act by inhibiting the cyclooxygenase enzyme (COX), which in turn prevents prostaglandin synthesis [40]. It is known that while COX-1 acts mainly on housekeeping physiological functions, COX-2 is normally activated in specific conditions such as inflammation [78]. Therefore, the therapeutic effect of NSAID drugs is mostly derived from their ability to inhibit COX-2, while most of their side-effects (gastrointestinal irritation, renal toxicity and inhibition of blood clotting) are caused by the inhibition of COX-1 [79]. The most frequently cited NSAIDs used for painful conditions in cattle are flunixin meglumine, meloxicam and ketoprofen [1,21,80]. Meloxicam is known to be a preferential COX-2 inhibitor [81], having a targeted action against inflammatory processes and optimal safety profile in cattle. Both ketoprofen and flunixin meglumine have a prevalent activity on COX-1. The half-life elimination of flunixin meglumine is 3 to 8 h, and ketoprofen has a short half-life of 0.42 h, and therefore requires extra dosing. In turn, the elimination half-life of meloxicam is found to be 24–26 h [82]. Other NSAIDs used in cattle are salicylate (COX-1 and -2) and carprofen (COX-2 selective and well-tolerated in cattle) [83]. Furthermore, it is important to note that with most NSAID treatments, milk discarding is mandatory for at least 24 h to prevent contamination with drug residues (see [83] for further review).
This entry is adapted from the peer-reviewed paper 10.3390/ani12020176
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