Melanocortin‐1 receptor influence in equine opioid sensitivity

Abstract

Summary Individual variation in opioid sensitivity can have a profound impact on the safety and efficacy of equine veterinary treatments, with the ability to adequately manage equine pain in a clinical setting currently limited. This review aims to explore the overlap between biological mechanisms associated with opioid metabolism and those mechanisms associated with coat colour in horses as has been documented in humans, with particular focus on the melanocortin‐1 receptor (MC1R) gene. In the future, the use of the MC1R coat colour genotype could help to indicate variable opioid sensitivities thereby greatly improving the use of opioids in clinical settings. The MC1R gene has a well‐established role in melanogenesis and pigment switching, but involvement in the pain‐modulating periaqueductal grey (PAG) descending pathway and in immune responses, both of which contain opioid receptors, has also been suggested in humans. However, this relationship between opioid metabolism and the connection to the three known MC1R variants (EE, Ee and Eea) in horses is yet to be explored.

The impact of opioid administration on the incidence of postanaesthetic colic in horses

“…Notably, the dosage necessary for morphine's analgesic effect significantly surpasses that needed for its gastrointestinal side effects, approximately fifty-fold in humans and fourfold in experimental animals ( 46 , 47 ). In horses, morphine administered intravenously at dosages as low as 0.05 mg/kg, half the dosage typically used clinically to provide analgesia, decreased propulsive gastrointestinal motility for up to 6 h and significantly reduced defecation frequency, faecal matter weight and moisture content ( 9 , 39 , 48 – 50 ).…”

“…Similarly, morphine, a μ -opioid agonist, has been shown to decrease gastrointestinal propulsive motility and to increase PAC rates after orthopaedic surgery four-fold when administered intravenously at a dosage of 0.08–0.3 mg/kg compared to no opioid or butorphanol ( 5 , 9 , 35 , 39 , 40 ). Conversely, two other studies found no association between peri-anaesthetic intravenous morphine administration at a dosage of 0.1–0.17 mg/kg and increased PAC risk ( 6 , 41 ).…”

Basal Reactivity Evaluated by Infrared Thermography in the “Caballo de Deporte Español” Horse Breed According to Its Coat Color

“…Conversely, some studies developed in humans found a lower pain threshold in red-haired people. Genetic variations in the MC1R gene have been identified related to alterations in pain perception and sensitivity to analgesics [ 14 , 54 , 55 ]. Although the pharmacodynamics involved in analgesics are complex, coat color in the horse could play an important role as a possible phenotypic indicator of variations in sensitivity to opioids [ 55 ] and thus, in the response to stressors.…”