Proposed multidimensional pain outcome methodology to demonstrate analgesic drug efficacy and facilitate future drug approval for piglet castration

Abstract

Castration of male piglets in the United States is conducted without analgesics because no Food and Drug Administration (FDA) approved products are labeled for pain control in swine. The absence of approved products is primarily due to a wide variation in how pain is measured in suckling piglets and the lack of validated pain-specific outcomes individually indistinct from other biological responses, such as general stress or inflammation responses with cortisol. Simply put, to measure pain mitigation, measurement of pain must be specific, quantifiable, and defined. Therefore, given the need for mitigating castration pain, a consortium of researchers, veterinarians, industry, and regulatory agencies was formed to identify potential animal-based outcomes and develop a methodology, based on the known scientific research, to measure pain and the efficacy of mitigation strategies. The outcome-based measures included physiological, neuroendocrine, behavioral, and production parameters. Ultimately, this consortium aims to provide a validated multimodal methodology to demonstrate analgesic drug efficacy for piglet castration. Measurable outcomes were selected based on published studies suggesting their validity, reliability, and sensitivity for the direct or indirect measurement of pain associated with surgical castration in piglets. Outcomes to be considered are observation of pain behaviors (i.e. ethogram defined behaviors and piglet grimace scale), gait parameters measured with a pressure mat, infrared thermography of skin temperature of the cranium and periphery of the eye, and blood biomarkers. Other measures include body weight and mortality rate. This standardized measurement of the outcome variable's primary goal is to facilitate consistency and rigor by developing a research methodology utilizing endpoints that are well-defined and reliably measure pain in piglets. The resulting methodology will facilitate and guide the evaluation of the effectiveness of comprehensive analgesic interventions for 3- to 5-day-old piglets following surgical castration.

Behavior of Piglets in an Observation Arena before and after Surgical Castration with Local Anesthesia

“…Therefore, perioperative pain management should go beyond treating acute castration-induced pain. Several review articles emphasized the relevance of observing specific pain behavior [7,31]. However, continuous observation is associated with high technological effort and labor input.…”

Piglets' acute responses to local anesthetic injection and surgical castration: Effects of the injection method and interval between injection and castration

“…This suggestion is supported, in our study, by comparable cortisol levels recorded in sham handled and castrated piglets. As a consequence of these known concerns, the present study examined acute responses to injection of anesthetic and castration across several indicators including cortisol, vocalizations and resistance movements, thereby taking a multi-modal approach as suggested by Sheil and Polkinghorne, and Baysinger et al ( 36 , 37 ).…”

Maximizing value and minimizing waste in clinical trials in swine: Selecting outcomes to build an evidence base

“…37 Recently, a consortium of researchers, industry, veterinarians, and regulatory agencies developed a methodology to measure pain associated with surgical castration in piglets. 38 These prior initiatives suggest that the swine industry could be successful in coming to consensus on core outcome sets. Creating core outcome sets will aid individual researchers in identifying outcomes and outcome measures to use in their trial and will facilitate synthesis of results from multiple trials.…”