anaigesia

ng highly effective analgesia that equates to (if not surpasses) that which is achieved for routine surgical procedures in veterinary clinics, such as spaying or castration of cats and dogs. New evidence is presented that Tri-Solfen® is also highly effective to alleviate pain associated with castration and tail docking in sheep. These developments are critically important because they indicate that there is a new way forward to address welfare concerns over mulesing, castration and tail docking and prevent conflicts while sustainable long term solutions such as genetic breeding are pursued and implemented. They highlight the need for a concerted research and development focus to fast track the availability of effective farm-based analgesia for all surgical husbandry procedures in livestock. BACKGROUND Surgical husbandry procedures in livestock, including mulesing, castration, tail docking and dehorning are associated with pain, bleeding and stress, yet are traditionally performed without analgesia or attempt at haemostasis. This not only results in production losses, but consumer concern for the welfare of animals undergoing these procedures is posing a significant threat to trade in several markets. The most obvious example is that of the Australian wool industry which is facing international boycotts of wool due to concern for the welfare of lambs undergoing mulesing. The pig industry in the European Union is facing a similar conflict, as consumer concern for the welfare of piglets undergoing castration without analgesia has led to a legislative ban on the procedure in some countries, and supermarket boycotts of produce from pigs castrated without analgesia in others. Conflicts such as these are set to escalate in the coming years. Animal welfare is becoming

…rubber rings,’ Despite extensive research, there has been little uptake of anaesthetic Keywords anaigesia; castration; cortisol; lambs; pain; tail docking approaches to reduce the pain and stress responses of lambs to castration…

ing CI exceptscore 0.5) less(A) FOS and proteinrepresentative images expression was observed in of FOS protein expression (B–E). (A)group the handling and in all local Significantly (AUCanaesthesia 95% CI groups, exceptexcept for less 0.5) the bupivacaine FOS protein than in group,expression was observed the NaCl group. (*) A significant effect. (B–E) Representative images of FOS protein expression in in the handling group the dorsal hornand of thein all local spinal cord inanaesthesia animals from thegroups, NaCl (B), except lidocaine for the bupivacaine (C), bupivacaine (D), and group, than in the handling (E) groups (bars indicate 30 µm). NaCl group. (*) A significant effect (p < 0.05). (B–E) Representative images of FOS protein expression in the dorsal horn of the spinal Additionally, cordexpression FOS protein in animals from the was evaluated NaCl only (B), lidocaine in animals that showed(C),no bupivacaine (D), BSupp and handling (E)patterns groupsthroughout the measured (bars indicate 30 µm).EEG epochs (Figure S2). 4. Discussion 4. DiscussionThe initial analysis of the changes in EEG patterns following the interdigital skin fold pinch, which induced a nociceptive withdrawal reflex, showed a strong biphasic re- The initial sponse. Asanalysis of was this stimulus theapplied changes in EEG to all animals patterns in an following identical manner without the anal- interdigital skin gesia, the data were pooled. This approach yielded a large number of samples. The bipha- fold pinch, which induced a nociceptive withdrawal reflex, showed sic EEG response consisted of an ‘early’ and a ‘late’ component. Similar EEG reactions a strong biphasic response. were As recorded this stimulus was following the applied scrotal to all skin incision andanimals

ing CI exceptscore 0.5) less(A) FOS and proteinrepresentative images expression was observed in of FOS protein expression (B–E). (A)group the handling and in all local Significantly (AUCanaesthesia 95% CI groups, exceptexcept for less 0.5) the bupivacaine FOS protein than in group,expression was observed the NaCl group. (*) A significant effect. (B–E) Representative images of FOS protein expression in in the handling group the dorsal hornand of thein all local spinal cord inanaesthesia animals from thegroups, NaCl (B), except lidocaine for the bupivacaine (C), bupivacaine (D), and group, than in the handling (E) groups (bars indicate 30 µm). NaCl group. (*) A significant effect (p < 0.05). (B–E) Representative images of FOS protein expression in the dorsal horn of the spinal Additionally, cordexpression FOS protein in animals from the was evaluated NaCl only (B), lidocaine in animals that showed(C),no bupivacaine (D), BSupp and handling (E)patterns groupsthroughout the measured (bars indicate 30 µm).EEG epochs (Figure S2). 4. Discussion 4. DiscussionThe initial analysis of the changes in EEG patterns following the interdigital skin fold pinch, which induced a nociceptive withdrawal reflex, showed a strong biphasic re- The initial sponse. Asanalysis of was this stimulus theapplied changes in EEG to all animals patterns in an following identical manner without the anal- interdigital skin gesia, the data were pooled. This approach yielded a large number of samples. The bipha- fold pinch, which induced a nociceptive withdrawal reflex, showed sic EEG response consisted of an ‘early’ and a ‘late’ component. Similar EEG reactions a strong biphasic response. were As recorded this stimulus was following the applied scrotal to all skin incision andanimals

on the skin of the breech and nine sites on the mulesing wound (Figure 1A and B). Evidence of local anaesthesia, allodynia (pain from stimuli such as light touch that is not usually painful), and/or primary and secondary hyperalgesia (exaggerated response to a painful stimulus directly in the damaged tissues or in surrounding undamaged tissues respectively), was assessed at each site. Typical LT and P induced involuntary reflexes and motor responses in the rump and head were graded by vigour. Rump response scores were graded as follows: 0 = no response; 1 = minor involuntary motor response such as local skin twitch, subcutaneous muscle twitch Figure 1. Diagram of sites of light touch and pain stimulation sensory or anal contraction; 2 = partial rump withdrawal reflex such as testing. A. On skin of the breech; B. Directly on the mulesing wound sites. multiple subcutaneous muscle group contraction and/or lifting of the tail; 3 = full rump withdrawal reflex with lifting of the rump off the cradle. Facial response scores were graded as follows: 0 = no response; 1 = minor facial ‘awareness’ such as eye observations and reports of behavioural changes in response to widening, blinking or nasal flaring; 2 = partial startle reflex of the mulesing and/or castration.1,2 A trained observer (veterinarian or head such as slight lifting of the snout or partial head rotation; 3 experience sheep handler, ‘blind’ to the treatment) was asked to = full startle reflex of the head, resulting in a major movement observe each lamb for a period of time sufficient to determine such as lifting head off the cradle, full head jerk or full head posture, gait and evoked behaviour, then grade each lamb on rotation. Scores for each site were added to achieve a total score a scale from 0 to 3

Such nutrient parti- 11. Grant C, Upton RN, Kuchel TR. Efficacy of intra-muscular analgesics for tioning provides substrates for the inflammatory and healing acute pain In sheep. Aust VetJ 1996;73:129-132. response to a surgical procedure. Therefore, a decrease in growth 12. Grant C, Upton RN. Comparison of the analgesic effects of xylazine in sheep via three different administration routes. Aust Vet J 2004;82:304-307. may be unavoidable in the short term even in the absence of pain 13. Mellor DJ, Stafford KJ. Acute castration and/or tailing distress and its allevi- and activation of the HPA axis. The measurement of individual ation in lambs. NZ Vet J 2000;48:33-43, feed intake may provide additional insight into these effects. 14. Hail LW, Clarke KW, Trim CM. General principles of local analgesia. in: Previous research in calves has suggested that analgesia for Veterinary Anaesthesia. 10th edn. WB Saunders, London, 2001:225—246., 15, Reich! M, Quinton D. Comparison of 1% lignocaine with 0.5% bupivacaine in castration may not alter reductions in individual feed intake in digital ring blocks. J Hand Surg 1987;12:375-376. the week after surgery.“ 16. Dobromylskyj, P, Flecknell PA, Lascelles BD et al. Management of post- operative and other acute pain. In: Flecknell PA, Waterman-Pearson A, editors. Conclusions Pain Management in animals, WB Saunders, London, 2000:81-145. 17. Chambers JP, Waterman AE, Livingston A. The effects of opioid and alpha Analgesics can moderate the pain response of lambs to mutlesing. 2 adrenergic blockade on non-steroidal anti-inflammatory drug analgesia in Greatest pain relief, as indicated by the behavioural and cortisol sheep. J Vet Pharmacol Ther 1995;18:161-166. tesponses to mulesing, was provided by the combined administration 18. Welsh

y, castration has traditionally been performed without anesthesia in the first week of life, although it has been scientifically shown that surgi- cal castration is a painful procedure [2,3]. Therefore, according to the German Animal Welfare Act, surgical castration of male piglets less than seven days of age without anesthesia will be forbidden in 2021 [4]. Gonadotropin-releasing-hormone (GnRH)-vaccination, boar fattening and surgical castration under general anesthesia are discussed as alternatives to castration without anesthesia. German law also permits the application of local veterinary medicinal products that are able to eliminate pain [4]. However, scientific evidence for the efficacy of local anesthesia for pain relief during castration of piglets is still lacking. For this reason, the discussion about local anesthesia as a legal method in Germany has resurfaced. As pain sensitivity can differ among different individuals, it is challenging to prove univer- sal pain elimination as requested by German law. According to the International Association for the Study of Pain (IASP), pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” [5]. One component of pain is nociception, defined as “the neural process of encoding noxious stimuli” whereby “consequences of encod- ing may be autonomic (e.g., elevated blood pressure) or behavioral (motor withdrawal reflex or more complex nocifensive behavior)”. The four steps in the development of feeling pain are transduction, transmission, modulation and perception. Nociception mainly refers to the first three components, lacking the conscious awareness and emotional component but including all vegetative, glycemic

y, castration has traditionally been performed without anesthesia in the first week of life, although it has been scientifically shown that surgi- cal castration is a painful procedure [2,3]. Therefore, according to the German Animal Welfare Act, surgical castration of male piglets less than seven days of age without anesthesia will be forbidden in 2021 [4]. Gonadotropin-releasing-hormone (GnRH)-vaccination, boar fattening and surgical castration under general anesthesia are discussed as alternatives to castration without anesthesia. German law also permits the application of local veterinary medicinal products that are able to eliminate pain [4]. However, scientific evidence for the efficacy of local anesthesia for pain relief during castration of piglets is still lacking. For this reason, the discussion about local anesthesia as a legal method in Germany has resurfaced. As pain sensitivity can differ among different individuals, it is challenging to prove univer- sal pain elimination as requested by German law. According to the International Association for the Study of Pain (IASP), pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” [5]. One component of pain is nociception, defined as “the neural process of encoding noxious stimuli” whereby “consequences of encod- ing may be autonomic (e.g., elevated blood pressure) or behavioral (motor withdrawal reflex or more complex nocifensive behavior)”. The four steps in the development of feeling pain are transduction, transmission, modulation and perception. Nociception mainly refers to the first three components, lacking the conscious awareness and emotional component but including all vegetative, glycemic

nonnoxious stimuli), and hypoesthesia (Lomax et al., suppressing the inflammatory cascade. The nerve end- 2008, 2010). Responses are recorded using a numerical ings in the damaged tissue are not exposed to inflamma- rating scale, despite concerns of subjectivity and sensi- Topical anesthesia and castration 4951 tory mediators that would cause them to become sensi- production animals, with product cost in addition to the tized, leading to decreased hyperalgesia. cost of employment of a veterinarian being significant Results from both techniques of sensory testing indi- barriers to general uptake (Stafford et al., 2005; Huxley cated no significant difference in secondary hyperalgesia and Whay, 2006). Options for analgesia are unlikely to of the periwound surface between treated and untreated be used in routine management procedures if their use calves 1 min after castration. Secondary hyperalgesia is is too time-consuming, costly, and generally impractical hypersensitivity in tissue adjacent to the wound and is for the farmer. It is likely that the use of analgesics may a consequence of central sensitization. This occurs as a become standard farm practice because of the falling result of peripheral sensitization (primary hyperalgesia) cost of most commonly used NSAID as more generic enhancing the pain responses of nociceptive neurons products become registered and available. However, in in the central nervous system (Ren and Dubner, 1999). the interim it is important to consider methods for effec- Dorsal horn neurons respond to peripheral inputs from tive and affordable alleviation of pain. the wound site and release chemical mediators that in- The topical anesthetic formulation examined in this crease central sensitization and lead to the perception of study has great

d repair. EMBO Rep 2002;3:575–582. infiltration with lidocaine on thermal and mechanical hyperalgesia after heat 37. Malatinsky J, Vigas M, Jurcovicova J, Jezova D, Garayova S, Minarikova M. The injury to the skin. Pain 1993;53:43–51. patterns of endocrine response to surgical stress during different types of anes- 26. Lam KW, Pun TC, Ng EH et al. Efficacy of preemptive analgesia for wound pain thesia and surgery in man. Acta Anaesthesiol Belg 1986;37:23–32. after laproscopic operations in infertile women: a randomised, double blind and 38. Fox SM, Mellor DJ, Firth EC et al. Changes in plasma cortisol concentrations placebo control study. Br J Obstet Gynaecol 2004;111:340–344. before, during and after analgesia, anaesthesia and anaesthesia plus ovariohys- 27. Pogatzki EM, Vandermeulen EP, Brennan TJ. Effect of plantar local anaesthetic terectomy in bitches. Res Vet Sci 1994;57:110–118. injection on dorsal horn neuron activity and pain behaviours caused by incision. 39. Hughan SC, Loose JM, Caddy DJ et al. Combined xylazine and ketamine as an Pain 2002;97:151–161. analgesic regimen in sheep. Aust Vet J 2001;79:207–211. 28. Paull DR, Lee C, Colditz IG et al. The effect of topical anaesthetic formulation, 40. Baldini G, Bagry H, Carli F. Depth of anesthesia with desflurane does not systemic flunixin and carprofen, singly or in combination, on cortisol and behav- influence the endocrine-metabolic response to pelvic surgery. Acta Anaesthesiol ioural responses of Merino lambs to mulesing. Aust Vet J 2007;85:98–106. Scand 2008;52:99–105. 29. Rolke R, Magerl W, Campbell KA et al. Quantitative sensory testing: a compre- hensive protocol for clinical trials. Eur J Pain 2006;10:77–88. (Accepted for publication 5 August 2009) BOOK REVIEW avj_551 74..81