Giovanna Lucrezia Costa ¹ Marco Tabbì ¹ Giuseppe Bruschetta ^1* Filippo Spadola ^1* Fabio Leonardi ² Fabio Bruno ^1,3* Nicola Maria Iannelli ^1* Patrizia Licata ¹ Francesco Macrì ¹ Eraldo Sanna Passino ^4* Daniele Macrì ^5* Claudia Interlandi ¹

• ¹ Department of Veterinary Sciences, University of Messina, Messina, Italy
• ² Department of Veterinary Medical Sciences, University of Parma, Parma, Emilia-Romagna, Italy
• ³ University of Messina, Messina, Italy
• ⁴ Department of Veterinary Medicine, University of Sassari, Sassari, Italy
• ⁵ Experimental Zooprophylactic Institute of Sicily (IZSSi), Palermo, Sicily, Italy

The aim of the study was to evaluate the analgesic efficacy of tapentadol in horses, through the determination of plasma serotonin concentration and adrenocortical response, as biomarkers of pain stress in chronic joint disorders. Thirty-six horses (twenty females and sixteen males) were divided into three groups of 12 subjects: group A, osteoarthritis (OA), grade 3-4 lameness; group B, OA, grade 5 lameness; group C, no OA, no lameness, were enrolled. The orthopedic examination included flexion tests, and radiological and ultrasound examinations. The degree of lameness has been estimated from 0 to 5 according to the American Association of Equine Practitioners (AAEP). Heart and respiratory rates (HR, RR) and blood pressure were recorded. Serotonin concentration and circulating cortisol were determined, at baseline and at the end of every week for four weeks. Biochemical parameters were recorded at baseline and at the end of treatment with tapentadol. Subjects with OA were treated with tapentadol 0.5 mg kg -1. The response to painful stimulus on flexion tests was evaluated using the NRS (modified Numeric Pain Rating Scale 0-7) from baseline and the CPS (Cumulative Pain score 0-4) after the first week of treatment with tapentadol.The lameness decreased along the timeline in both groups (score from 3-4 to 1 in group A and score from 5 to 1 in group B) (p<0.05). The NRS score decreased along the timeline (p<0.05), from mild pain to no pain in group A (score 1-3 to 0) and from moderate pain to no pain in group B (score from 4 to 0). Physiological variables remained within the physiological range along the timeline. Cumulative Pain score scores ranged from 0.5 to 4 in group A and 1.5 to 7, in group B (p=0.008). Serotonin concentrations remained unchanged along the timeline in all groups (p=1.000) but in OA groups the concentrations were lower than control (p<0.001). Circulating cortisol was decreased than baseline in subjects treated with tapentadol (p<0.001). Tapentadol is effective in OA pain management in horses. Serotonin and cortisol may be utilized as biomarkers in the pain stress response. Serotonin can also determine the state of well-being of patients.