*Review* **Optimal Methods of Documenting Analgesic <sup>E</sup>**ffi**cacy in Neonatal Piglets Undergoing Castration**

**Meredith Sheil 1,\* and Adam Polkinghorne 2,3**


Received: 27 July 2020; Accepted: 13 August 2020; Published: 19 August 2020

**Simple Summary:** Surgical castration in piglets is widely used in commercial pig production systems; however, it may cause pain and stress to the animal. There is an urgen<sup>t</sup> need to develop effective pain-relieving medications to use for this procedure. Such products must meet high standards of proof confirming that they are effective. This requires undertaking trials to determine the duration and severity of pain that piglets experience during and after castration, and the extent of pain reduction in anaesthetic/analgesic treated piglets. Unfortunately, responses to pain may be transient, subtle, or variably expressed. Furthermore, there is no simple "gold standard" method to measure pain in neonatal piglets. Instead, researchers must rely on using a range of indirect measures of pain of varying reliability. Without understanding the nature of expression of piglet pain, and the reliability of test measures to detect it, there is the potential of misinterpreting trial outcomes. Although there is a high degree of variability in the literature of test methods employed and outcomes obtained, there is nevertheless a growing body of evidence to sugges<sup>t</sup> that some piglet responses to pain induced by castration, are more consistently reproduced and specific to the pain experienced during castration than others. In this narrative review, we examine the potential indicators of pain in neonatal piglets undergoing castration to determine the optimal methods currently available to most accurately detect pain and assess pain mitigation.

**Abstract:** Analgesic products for piglet castration are critically needed. This requires extensive animal experimentation such as to meet regulatory-required proof of efficacy. At present, there are no validated methods of assessing pain in neonatal piglets. This poses challenges for investigators to optimize trial design and to meet ethical obligations to minimize the number of animals needed. Pain in neonatal piglets may be subtle, transient, and/or variably expressed and, in the absence of validated methods, investigators must rely on using a range of biochemical, physiological and behavioural variables, many of which appear to have very low (or unknown) sensitivity or specificity for documenting pain, or pain-relieving effects. A previous systematic review of this subject was hampered by the high degree of variability in the literature base both in terms of methods used to assess pain and pain mitigation, as well as in outcomes reported. In this setting we provide a narrative review to assist in determining the optimal methods currently available to detect piglet pain during castration and methods to mitigate castration-induced pain. In overview, the optimal outcome variables identified are nociceptive motor and vocal response scores during castration and quantitative sensory-threshold response testing and pain-associated behaviour scores following castration.

**Keywords:** piglet; castration; pain; behaviour; peri-operative; vocalisation; nociception; neonate; anaesthesia; analgesia
