Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets

Abstract

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.

Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration andtail‐docking

“…In addition, studies have suggested that plasma drug concentrations do not always reflect tissue drug concentrations, particularly for NSAIDs, which may become "trapped" at sites of inflammation (Brune & Furst, 2007;Lees et al, 2004;Messenger et al, 2016). The previous portion of this study shows that NSAIDs given before processing procedures may reduce pain and inflammation associated with castration and tail docking (Nixon et al, 2021), and interstitial fluid (ISF) drug concentrations were also previously reported (Nixon et al, 2020). Interstitial fluid collected via in vivo ultrafiltration allows the measurement of only the pharmacologically active, proteinunbound drug concentrations, critical to assess drug concentrations directly at the tissue level and may better correlate with the antiinflammatory effect than plasma concentrations.…”

“…Plasma and ISF drug, plasma cortisol and ISF PGE2 were analyzed as previously reported (Nixon et al, 2020(Nixon et al, , 2021…”

“…The primary mechanism of action for NSAIDs is inhibition of the cyclooxygenase (COX) enzyme. The COX‐2 isoform is inducible and upregulated by tissue damage and inflammatory stimuli, increasing production of prostaglandins, and prostaglandin E2 (PGE2) increases following castration and tail docking in piglets (Fosse et al, 2008; Nixon et al, 2021). Prostaglandins contribute to pain signaling by activating and sensitizing nociceptors (Davidson et al, 2014), leading to an increase in the magnitude of response to noxious stimulation.…”

“…In response to stress, corticotrophin‐releasing hormone (CRH) is released by the hypothalamus, stimulating the secretion of adrenocorticotrophic hormone (ACTH) from the anterior pituitary which acts on the adrenal gland to produce cortisol. Prostaglandins also directly stimulate ACTH and cortisol release (Sheil et al, 2020), and piglet castration research commonly uses cortisol as an indirect measure of pain (Bates et al, 2014; Ison et al, 2016; Keita et al, 2010; Kluivers‐Poodt et al, 2012; Nixon et al, 2021; Prunier et al, 2005; Sutherland et al, 2011). A panel of experts performed a systematic review of available data related to pain mitigation during piglet husbandry procedures.…”

“…following castration and tail docking in piglets (Fosse et al, 2008;Nixon et al, 2021). Prostaglandins contribute to pain signaling by activating and sensitizing nociceptors (Davidson et al, 2014), leading to an increase in the magnitude of response to noxious stimulation.…”