Development and validation of pain models in food animals
Project Summary
Each year, more than 65 million piglets, 1 million goats and 15 million calves in the U.S. undergo painful
procedures such as tail docking, disbudding, and castration. Livestock also commonly develop painful
conditions such as lameness during the production cycle. Misalignment between industry guidelines and
on-farm analgesic use threatens consumer confidence in livestock production practices. One factor
contributing to the low adoption rate of pain mitigation protocols on farms is the lack of FDA-approved
analgesic drugs.
Our long-term goal is to improve on-farm animal welfare by controlling pain in a manner that is safe for
the animal and the consumer, and compliant with U.S. regulations. The specific objective of this proposal
is to develop models which reliably and consistently evaluate the efficacy of analgesics in food animals in
support of neww drug approvals. A central hypothesis of this proposal is that there are interactions
between measuring current standard behavioral outcomes and measuring analytical biomarkers which
affect how we perceive pain in animals, and therefore how efficacy of an analgesic is evaluated in the
approval process. We also hypothesize that more advanced analysis of analgesic pharmacokinetics and
pharmacodynamics in food animals will improve modeling of optimal regimens.
Painful processes addressed through the 5 specific aims of this proposal include footrot and castration in
goats, dehorning and castration in calves, and castration and tail docking in piglets. In goats and calves,
first we seek to establish the optimal pain biomarkers (behavioral and analytic) and evaluate the effect of
collecting concurrent behavioral and analytic biomarkers on the values determined for each. Secondly,
the efficacy of two doses of transdermal flunixin meglumine are evaluated for controlling pain associated
with the indicated pain process, and then the pharmacokinetics/pharmacodynamics in relation to pain
biomarkers are characterized. In swine, the first phase seeks to create a pharmacokinetic/
pharmacodynamic model to describe the analgesic efficacy of flunixin meglumine in castration and tail
docking of swine. The second swine phase validates predictions made by this model.
This novel proposal will advance our understanding of measuring pain and create a more standardized
process to support investigation and approval of existing and candidate analgesic drugs for food animal
species. The novel pharmacokinetic/pharmacodynamic components of this project advance our
understanding of modeling analgesic drug efficacy and support optimal regimen development prior to
clinical studies.