title: Assessing experimental visceral pain in dairy cattle: A pilot, prospective, blinded, randomized, and controlled study focusing on spinal pain proteomics.
abstract: Few studies have verified the validity of behavioral and physiological methods of pain assessment in cattle. This prospective, blinded, randomized controlled experimental study aimed to validate different methods of pain assessment during acute and chronic (up to 21 d postintervention) conditions in dairy cattle, in response to 3 analgesic treatments for traumatic reticuloperitonitis. Cerebrospinal fluid (CSF) biomarkers and mechanical sensitization were measured as indicators of centralized pain. Proteomics in the CSF were examined to detect specific (to pain intensity) and sensitive (responsive to analgesia) markers. Recordings of spontaneous behavior with video analysis, telemetered motor activity, pain scales, electrodermal activity, and plasma cortisol concentration were quantified at regular intervals. Cows were assigned to group 1 (n=4, standard control receiving aspirin), group 2 (n=5, test group receiving preemptive tolfenamic acid), or group 3 (n=3, positive control receiving preemptive multimodal analgesia composed of epidural morphine, plus tolfenamic acid and butorphanol). Rescue analgesia was administered as needed. Generalized estimating equations tested group differences and the influence of rescue analgesia on the measurements. All 3 groups demonstrated a long-term decrease in a CSF protein identified as transthyretin. The decrease in transthyretin expression inversely correlated with the expected level of analgesia (group 1<2<3). Moreover, in group 1, CSF noradrenaline decreased long term, cows were hypersensitive to mechanical stimulation, and they demonstrated signs of discomfort with higher motor activity and "agitation while lying" recorded from video analysis. Decreased "feeding behavior," observer-reported pain scales, electrodermal activity, and plasma cortisol concentration were inconsistent to differentiate pain intensity between groups. In summary, changes in CSF biomarkers and mechanical sensitization reflected modulation of central pain in dairy cows. The spontaneous behavior "agitation while lying" was the only behavioral outcome validated for assessing acute and chronic pain in this visceral pain model.
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Rialland
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Otis
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: M-L
authors.initials: ML
authors.lastname: de Courval
authors.affiliation: Department of Clinical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Mulon
authors.affiliation: Department of Clinical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Harvey
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Bichot
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Gauvin
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, S7N 5B4, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Livingston
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Beaudry
authors.affiliation: Department of Pathology and Microbiology, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Hélie
authors.affiliation: Department of Clinical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Frank
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada.
authors.forename: J R E
authors.initials: JR
authors.lastname: Del Castillo
authors.affiliation: Quebec Research Group in Animal Pharmacology (GREPAQ), Department of Veterinary Biomedical Sciences, Faculté de Médecine Vétérinaire-Université de Montréal, Saint-Hyacinthe, QC, J2S 7C6, Canada. Electronic address: eric.troncy@umontreal.ca.
authors.forename: E
authors.initials: E
authors.lastname: Troncy
mesh_terms: D000698:Analgesia / Q000379:methods / Q000662:veterinary; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002395:Catecholamines / Q000134:cerebrospinal fluid; D002417:Cattle; D059408:Pain Management / Q000662:veterinary; D010147:Pain Measurement / Q000379:methods / Q000662:veterinary*; D010865:Pilot Projects; D011228:Prealbumin / Q000134:cerebrospinal fluid; D011446:Prospective Studies; D040901:Proteomics; D059265:Visceral Pain / Q000175:diagnosis* / Q000188:drug therapy* / Q000662:veterinary*
chemical_list: D000700:Analgesics; D015415:Biomarkers; D002395:Catecholamines; D011228:Prealbumin
keywords: animal behavior; central sensitization; pain metrology; preemptive multimodal analgesia