** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** IN RESPONSE TO THE CRITICAL NEED FOR EFFECTIVE AND APPROVED PAIN-RELIEF DRUGS FOR USE ON U.S. LIVESTOCK OPERATIONS, THIS PARTNERSHIP PROPOSAL WITH THE UNIVERSITY OF ADELAIDE AND THE U.S. FOOD AND DRUG ADMINISTRATION (FDA) WILL IDENTIFY GENETIC MARKERS OF PAIN IN THE BLOOD OF PIGS AND CATTLE. EACH YEAR, MORE THAN 65 MILLION PIGLETS AND 15 MILLION CALVES IN THE U.S. UNDERGO PROCEDURES SUCH AS TAIL DOCKING, DISBUDDING AND CASTRATION. CONCERN ABOUT THE NEGATIVE IMPACT OF THESE PROCEDURES ON ANIMAL WELFARE HAS CONTRIBUTED TO THE DEVELOPMENT OF NEW GUIDELINES THAT REQUIRE THE USE OF PAIN MANAGEMENT AT THE TIME OF THESE PROCEDURES. HOWEVER, THE ON-FARM IMPLEMENTATION OF THESE GUIDELINES HAS BEEN CHALLENGING. ONE FACTOR CONTRIBUTING TO THE LOW ADOPTION RATE OF PAIN MITIGATION PROTOCOLS ON FARMS IS THE LACK OF FDA-APPROVED ANALGESIC DRUGS. IN A SURVEY PUBLISHED IN 2021, 89.5% OF VETERINARIANS REPORT THAT FEDERAL REGULATIONS LIMIT THEIR ABILITY TO USE ANALGESIC DRUGS. MOREOVER, 50% OF RESPONDENTS ATTRIBUTE A REDUCTION IN THEIR ANALGESIC USE TO CONCERN ABOUT ADMINISTERING DRUGS THAT LACK FDA APPROVAL. 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. MEASUREMENT OF PAIN IN FARM ANIMALS IS CURRENTLY BASED ON THE ASSESSMENT OF BEHAVIORAL AND HORMONAL OUTCOMES. THESE OUTCOMES GENERALLY LACK DIAGNOSTIC SPECIFICITY AND SENSITIVITY. THE TRANSCRIPTOME IS COMPRISED OF MESSENGER RNAS (MRNAS) THAT TRANSLATE THE GENETIC CODE TO PROTEINS UNDERPINNING BIOLOGICAL PROCESSES IN THE BODY, AND MICRORNAS (MIRS) THAT REGULATE GENE EXPRESSION AND FUNCTION AS CHEMICAL MESSENGERS TO MEDIATE CELL TO CELL COMMUNICATION. THE PRIMARY GOAL OF THIS PROPOSAL IS TO SUPPORT THE APPROVAL OF PAIN RELIEF DRUGS AND ASSIST FUTURE ON-FARM ANIMAL WELFARE ASSESSMENT, THROUGH THE VALIDATION OF NOVEL TRANSCRIPTOME BLOOD MARKERS OF PAIN IN CATTLE AND SWINE.SPECIFIC AIM 1 WILL VALIDATE GENETIC BIOMARKERS OF PAIN COMPARED WITH NO PAINSPECIFIC AIM 2 WILL VALIDATE GENETIC BIOMARKERS TO ASSESS THE EFFETIVENESS OF PAIN-ELIEF DRUGSSPECIFIC AIM 3 WILL ESTABLISH THE DIAGNOSTIC PERFORMANCE OF GENETIC BIOMARKERS OF PAIN AND PAIN-RELIEVING EFFECTS IN FIELD TRIALSCOMPLETION OF THE PROPOSED SPECIFIC AIMS WILL ADDRESS TWO STATED PRIORITIES WITHIN THE ANIMAL WELFARE SECTION (CODE A1251) BY 1) USING FUNCTIONAL GENOMICS TO ADVANCE OBJECTIVE MEASURES OF ANIMAL WELFARE AND 2) WORKING TOWARDS INTERVENTIONS THAT ALLEVIATE PAIN AND STRESS ASSOCIATED WITH PAINFUL PROCEDURES.