Impact of Transmammary-Delivered Meloxicam on Biomarkers of Pain and Distress in Piglets after Castration and Tail Docking

Abstract

To investigate a novel route for providing analgesia to processed piglets via transmammary drug delivery, meloxicam was administered orally to sows after farrowing. The objectives of the study were to demonstrate meloxicam transfer from sows to piglets via milk and to describe the analgesic effects in piglets after processing through assessment of pain biomarkers and infrared thermography (IRT). Ten sows received either meloxicam (30 mg/kg) (n = 5) or whey protein (placebo) (n = 5) in their daily feedings, starting four days after farrowing and continuing for three consecutive days. During this period, blood and milk samples were collected at 12-hour intervals. On Day 5 after farrowing, three boars and three gilts from each litter were castrated or sham castrated, tail docked, and administered an iron injection. Piglet blood samples were collected immediately before processing and at predetermined times over an 84-hour period. IRT images were captured at each piglet blood collection point. Plasma was tested to confirm meloxicam concentrations using a validated high-performance liquid chromatography-mass spectrometry method. Meloxicam was detected in all piglets nursing on medicated sows at each time point, and the mean (± standard error of the mean) meloxicam concentration at castration was 568.9±105.8 ng/mL. Furthermore, ex-vivo prostaglandin E2 (PGE2) synthesis inhibition was greater in piglets from treated sows compared to controls (p = 0.0059). There was a time-by-treatment interaction for plasma cortisol (p = 0.0009), with meloxicam-treated piglets demonstrating lower cortisol concentrations than control piglets for 10 hours after castration. No differences in mean plasma substance P concentrations between treatment groups were observed (p = 0.67). Lower cranial skin temperatures on IRT were observed in placebo compared to meloxicam-treated piglets (p = 0.015). This study demonstrates the successful transfer of meloxicam from sows to piglets through milk and corresponding analgesia after processing, as evidenced by a decrease in cortisol and PGE2 levels and maintenance of cranial skin temperature.

Acute physiological responses to castration-related pain in piglets: the effect of two local anesthetics with or without meloxicam

“…Bates et al (2014) found a lower cranial skin temperature in control piglets compared with piglets receiving transmammarydelivered meloxicam; however, the temperature differences were not significant in other anatomical sites (left ear, right ear and snout tip). Therefore, the measurement of temperature in the groin area might explain the failure in detecting effects of the local anesthetic and meloxicam on skin surface temperature.…”

“…Meloxicam also had a significant effect on behavioral responses 1 h to 5 days after castration (Keita et al, 2010;Hansson et al, 2011;Kluivers-Poodt et al, 2013). Meloxicam also caused a decrease in serum concentration of cortisol in piglets when sows, after farrowing, received meloxicam orally so that it was administered to piglets through maternal milk (Bates et al, 2014).…”

A Review of Pain Assessment in Pigs

“…SP was elevated in compressed spinal nerve roots, compared with uncompressed controls, in a porcine model (166). Piglet castration did not elicit a plasma SP response at 3 days old (167) or in piglets that were castrated, tailed docked, and had iron administered at 5 days old (168). A study of castration indicated that SP could be a useful pain biomarker in calves (169), and SP has been shown to have a systemic role (170), indicating that measurement of systemic concentrations, rather than just at the site of damage, could be useful.…”

“…In response to physical or psychological 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. Studies have investigated cortisol/ACTH levels in pigs with and without (controls/shams) a painful condition (68, 70, 72, 88, 93, 94, 104, 156, 171, 172), before, during, or after (68, 173–175), with or without anesthesia or analgesia (72, 78, 111, 156, 168), and associated with the severity of the pain (68, 88, 101, 171, 176). …”

Non-Steroidal Anti-Inflammatory Drugs in Food Producing Animals

“…• Extralabel use of an approved human drug is not permitted in food producing animals if an approved animal drug can be use in extralabel fashion • Extralabel drug use is permitted only by the order of a licensed veterinarian within the context of a valid veterinarian-client-patient relationship • No other approved animal drug is labelled and contains the same active ingredient in the required dosage and concentration, except when the veterinarian finds the approved drug to be clinically ineffective • The health of the animals is threatened, or suffering or death may result from failure to treat • Extralabel drug use is not permitted to enhance production or feed additives • Assure that the identity of the treated animal is recorded and records are maintained • Appropriate labelling information including withdrawal times for meat, milk and eggs as specified by the veterinarian must be provided • Extralabel use that may result in residues above an established safe level or tolerance or present a risk to public health is not permitted (Lin and Walz., 2014;Bates et al, 2014) …”