The pain experience is a combination of sensory and emotional components. Pain causes fear, stress and anxiety, negatively impacting quality of life. It also delays recovery and induces behavioral changes that affect the owner-companion animal bond.¹ Treatment of pain relies on a multimodal approach involving pharmacological and non-pharmacological techniques. Particularly for pharmacological treatment of acute pain, the use of local anesthetic techniques, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are always recommended.¹ Nevertheless, NSAIDs might be contraindicated in some circumstances,² and the recent opioid crises have highlighted the importance of alternatives to opioids. In this scenario, adjuvant analgesics come into play. Adjuvant analgesics are drugs indicated for primary non-pain conditions but that were found to be efficacious in analgesia either when used alone or in combination with other analgesics.(3) The use of adjuvant analgesics such as ketamine, gabapentin, ½–2 agonists, and lidocaine (when administered systemically) is performed both in human and veterinary medicine for the management of postoperative pain.

Although there are few studies in small animals, some recent publications have shown interesting results. For example, in one study, cats undergoing ovariohysterectomy and being administered buprenorphine as part of the premedication were evaluated. One group received the oral administration of gabapentin approximately 12 and 2h prior to surgery showed (test group); another received a placebo at these same time points (negative control); and the third group received the same placebo and meloxicam (positive control). Although the prevalence of rescue analgesia using a multidimensional composite pain scale was not different, it would be if it were based on the Glasgow pain scale (rCMPS-F).⁴ Those authors discussed the lack of power due to small sample size and emphasized the promising results of gabapentin as an antihyperalgesic in the management of acute pain. In fact, systematic reviews and meta-analyses from studies in people reveal that perioperative administration of gabapentin reduces acute postoperative pain after surgery.⁵ Other authors have also reported the use of adjuvant analgesics such as gabapentin, ketamine and tramadol in cats after trauma or undergoing major surgical procedures.⁶

In a prospective randomized and blinded clinical study involving dogs undergoing forelimb amputation, those that received a low-dose ketamine infusion for up to 18 hours after surgery had significantly lower pain scores and were significantly more active on post-operative day 3 than dogs in the control group receiving saline infusions.⁷ Constant rate infusions of lidocaine, ketamine, dexmedetomidine alone or in combination have been studied in dogs undergoing ovariohysterectomy. The combination lidocaine-ketamine-dexmedetomidine provided superior postoperative analgesia when compared with saline or each drug administered alone.⁸

Controversies on the use of adjuvant analgesics also exist. For example, maropitant is a neurokinin-1 receptor antagonist that blocks the effects of excitatory neurotransmitter substance P. Although the drug is labelled for treatment of acute vomiting in cats and dogs, it has been anecdotally used for the management of postoperative pain. Some studies have shown decreases in minimum alveolar concentrations of sevoflurane during ovarian ligament stimulation in cats and dogs.^9,10 Maropitant might aid with patient comfort as anti-emetic, but at this point, it remains unknow whether it provides any analgesic effect.

Appropriate management of acute pain is essential for providing state-of-the-art patient care. However, it has to rely on solid evidence-based medicine. Understanding these drugs and how to use them can have a great impact on animal health and welfare. This lecture will present and discuss the current evidence-based knowledge on the use of adjuvant analgesics for the management of acute pain.

References

1.  Mathews K, Krone P, Lascelles D, Nolan A, Robertson S, Steagall P, et al. Guidelines for recognition, assessment and treatment of pain: WSAVA Global Pain Council members and co-authors of this document. 2014;55(6):E10–68.

2.  Monteiro-Steagall BP, Steagall PVM, Lascelles BDX. systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. J Vet Intern Med [Internet]. 2013;27(5):1011–9. Available from: http://doi.wiley.com/10.1111/jvim.12127.

3.  Lui F, Ng K-FJ. Adjuvant analgesics in acute pain. Expert Opin Pharmacother [Internet]. 2011 Feb 22 [cited 2019 Mar 28];12(3):363–85. Available from: www.tandfonline.com/doi/full/10.1517/14656566.2011.521743

4.  Steagall PV., Benito J, Monteiro BP, Doodnaught GM, Beauchamp G, Evangelista MC. Analgesic effects of gabapentin and buprenorphine in cats undergoing ovariohysterectomy using two pain-scoring systems: a randomized clinical trial. J Feline Med Surg. 2017.

5.  Chamberlain R, Arumugam S, Lau C. Use of preoperative gabapentin significantly reduces postoperative opioid consumption: a meta-analysis. J Pain Res [Internet]. 2016 Sep [cited 2019 Mar 28]; 9:631–40. Available from: www.ncbi.nlm.nih.gov/pubmed/27672340

6.  Steagall PVM, Monteiro-Steagall BP. Multimodal analgesia for perioperative pain in three cats. J Feline Med Surg. 2013;15(8):737–43.

7.  Wagner AE, Walton JA, Hellyer PW, Gaynor JS, Mama KR. Use of low doses of ketamine administered by constant rate infusion as an adjunct for postoperative analgesia in dogs. J Am Vet Med Assoc [Internet]. 2002 Jul 1 [cited 2019 Mar 28];221(1):72–5. Available from: www.ncbi.nlm.nih.gov/pubmed/12420827

8.  Gutierrez-Blanco E, Victoria-Mora JM, Ibancovichi-Camarillo JA, Sauri-Arceo CH, Bolio-González ME, Acevedo-Arcique CM, et al. Postoperative analgesic effects of either a constant rate infusion of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine after ovariohysterectomy in dogs. Vet Anaesth Analg [Internet]. 2015 May [cited 2019 Mar 28];42(3):309–18. Available from: www.ncbi.nlm.nih.gov/pubmed/25039918

9.  Niyom S, Boscan P, Twedt DC, Monnet E, Eickhoff JC. Effect of maropitant, a neurokinin½1 receptor antagonist, on the minimum alveolar concentration of sevoflurane during stimulation of the ovarian ligament in cats. Vet Anaesth Analg [Internet]. John Wiley & Sons, Ltd (10.1111); 2013 Jul 1 [cited 2019 Mar 28];40(4):425–31. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1467298716302896

10.  Boscan P, Monnet E, Mama K, Twedt DC, Congdon J, Steffey EP. Effect of maropitant, a neurokinin 1 receptor antagonist, on anesthetic requirements during noxious visceral stimulation of the ovary in dogs. Am J Vet Res [Internet]. 2011 Dec [cited 2019 Mar 28];72(12):1576–9. Available from: http://avmajournals.avma.org/doi/abs/10.2460/ajvr.72.12.1576