Outcomes from Experimental Testing of Nonsteroidal Anti-Inflammatory Drug (NSAID) Administration during the Transition Period of Dairy Cows

Abstract

During the transition period, dairy cows experience great physiological stress caused by changes in metabolism and in the immune and endocrine systems. A pro-inflammatory state is another difficulty faced by even apparently healthy animals. The most significant negative consequences of inflammation in dairy cows are substantial impairment of milk production and deleterious effects on cows’ health in extreme cases. Nonetheless, a certain degree of inflammation is necessary to sustain physiological adaptations. In recent years, many studies have attempted to determine whether the use of nonsteroidal anti-inflammatory drugs (NSAID) in the transition period of dairy cows could positively affect milk production and cows’ health by controlling the inflammation status. This literature indicates that NSAIDs that act as preferential inhibitors of cyclooxygenase-1 (COX-1) activity show important side effects (e.g., increased risk of retained placenta, culling, or metritis) even if milk production is, on average, ameliorated. In contrast, preferential inhibitors of cyclooxygenase-2 (COX-2) activity have overall positive effects on cows’ health, with potential beneficial effects on milk production. Furthermore, it is important to note that with certain NSAID treatments, milk discarding is mandatory to prevent contamination with drug residues, but increased milk production can compensate for the loss of milk revenue during the withdrawal period.

Analgesia during Parturition in Domestic Animals: Perspectives and Controversies on Its Use

“…In dairy cows, for example, administering NSAIDs of the inhibitor of COX-1 type produced adverse effects such as retained placenta, metritis, and culling, because COX-1 is constitutive and participates in diverse physiological functions. In contrast, preferential inhibitors of COX-2 have been related to benefits for the health and productivity of females [ 79 , 80 ].…”

Alteration in Activity Patterns of Cows as a Result of Pain Due to Health Conditions

“…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).…”

“…The reason why flunixin meglumine did not show these expected effects remains unclear. Several factors, such as the short half-life elimination of flunixin meglumine [ 83 ] or delayed administration after challenge (from 4 h to 24 h) [ 95 , 100 ], could have influenced the result. Additional research including the effect of other NSAIDs on experimentally induced mastitis on lying time should include a closer administration before or after challenge and/or a repeated dose administration.…”

“…Most dairy cows experience a physiological subacute inflammation during the first days after calving [ 134 ]. If the degree of inflammation exceeds a certain level, it becomes harmful, impairing normal lactation [ 83 ]. In fact, around the time of birth, the levels of acute-phase proteins (such as haptoglobin and serum amyloid protein) increase considerably in response to inflammation, tissue damage and, thus, pain [ 135 ].…”

Effects of dietary butyrate supplementation and oral nonsteroidal antiinflammatory drug administration on uterine inflammation and interval to first ovulation in postpartum dairy cows

“…It has been suggested that NSAID are likely more effective for cows experiencing calving difficulties (Laven et al, 2012) or inflammation, but when given to healthy cows, it may suppress inflammatory signaling in the immune system and lead to infections (Trimboli et al, 2020). Overall, it appears that there are risks associated with administering NSAID as a blanket treatment to all transition cows as inflammation is necessary to adapt to lactation; thus, it may be advisable to only provide NSAID to cows experiencing excessive inflammation following a difficult calving or other inflammatory conditions.…”