Pharmacokinetics and effect of intravenous meloxicam in weaned Holstein calves following scoop dehorning without local anesthesia

Abstract

BackgroundDehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 – 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia.ResultsPlasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T½α = 0.22 ± 0.087 h) and a slower elimination phase (mean T½β = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042).ConclusionsTo our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.

Effects of sample handling methods on substance P concentrations and immunoreactivity in bovine blood samples

“…Liquid chromatography-tandem mass spectrometry SP [1][2][3][4][5][6][7][8][9][10][11] Parent substance P molecule composed of 11 amino acids SP [3][4][5][6][7][8][9][10][11] Metabolite of substance P composed of the last 9 C-terminal amino acids SP [7][8][9][10][11] Metabolite of substance P composed of the last 5 C-terminal amino acids been evaluated as a response variable that may be more specific for the measurement of pain in animals. [3][4][5][6][7][8][9][10] Substance P is a biologically active peptide that has a role in neural transmission of nociceptive signals from peripheral sites to the CNS.…”

“…[3][4][5][6][7][8][9][10] Substance P is a biologically active peptide that has a role in neural transmission of nociceptive signals from peripheral sites to the CNS. 11 Substance P is released by peptidergic peripheral sensory nerve fibers at central synaptic junctions in the dorsal horn of the spinal cord and at peripheral nerve terminals, where the peptide has a role as a signaling molecule in the transmission of pain impulses and the induction of inflammation and central sensitization.…”

“…The substance P parent molecule is a peptide composed of 11 amino acids with an amidated carboxyl terminus (arginine-prolinelysine-proline-glutamine-glutamine-phenylalaninephenylalanine-glysine-leucine-ethionine-NH 2 ). Enzymes that cleave SP [1][2][3][4][5][6][7][8][9][10][11] include members of the serine and metalloprotease families: angiotensin I-converting enzyme, aminopeptidase, neutral endopeptidase, dipeptidyl peptidase IV, and postproline cleaving enzyme. 13,14 Enzymes of these classes require inhibitors with specific affinity for their catalytic sites; therefore, protection of SP [1][2][3][4][5][6][7][8][9][10][11] from enzymatic degradation may require at least 2 inhibitor types.…”

“…Enzymes that cleave SP [1][2][3][4][5][6][7][8][9][10][11] include members of the serine and metalloprotease families: angiotensin I-converting enzyme, aminopeptidase, neutral endopeptidase, dipeptidyl peptidase IV, and postproline cleaving enzyme. 13,14 Enzymes of these classes require inhibitors with specific affinity for their catalytic sites; therefore, protection of SP [1][2][3][4][5][6][7][8][9][10][11] from enzymatic degradation may require at least 2 inhibitor types. Various degradation products are derived from SP [1][2][3][4][5][6][7][8][9][10][11] and are named in accordance with the amino acids they contain.…”

“…Various degradation products are derived from SP [1][2][3][4][5][6][7][8][9][10][11] and are named in accordance with the amino acids they contain. For example, cleavage of SP [1][2][3][4][5][6][7][8][9][10][11] between the number 2 and number 3 amino acids (proline and lysine) results in the formation of 2 fragments: an arginine-proline fragment and SP [3][4][5][6][7][8][9][10][11] . Fragments containing the 5 C-terminal amino acids (fragments SP 7-11 through SP [1][2][3][4][5][6][7][8][9][10][11] ) have similar biological effects, although the potency of such effects decreases with fewer amino acids.…”