Katrina Lafferty
BFA, RLAT, CVT, VTS (Anesthesia & Analgesia)
Katrina graduated from DePaul University with her bachelor of fine arts degree in theatre and obtained her veterinary medical technology degree from Joliet Junior College. She has worked at the University of Wisconsin-Madison (UW) School of Veterinary Medicine since 2005, mostly in the anesthesia and pain management department. She also spent a 4-year stint at the UW National Primate Center in the anesthesia and surgery department. Katrina has anesthetized everything from a 2-day-old calf to a 4-week-old kitten to a 60-year-old tortoise, as well as a veritable menagerie of other species. Her passion is all things anesthesia and pain management, particularly in exotic species.
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In veterinary medicine, opioids are the mainstay of treatment for most pain states, from mild to severe. However, in human medicine, opioid therapy can lead to addiction and overdose death, bringing to the forefront an opioid crisis. The trickle-down effect for the veterinary world is an opioid shortage.
This article will discuss the pros and cons to various pharmacologic opioid-sparing analgesic drugs and techniques.
Take-Home Points
- While opioids provide analgesia for many types of situations, they are not the only option for managing acute, postoperative, or chronic pain.
- A fundamental understanding and regular usage of a pain score system will help target and refine the need for analgesic management.
- Locoregional blocks and constant-rate infusions offer accessible opioid-sparing options that can be applied to many cases.
Human and veterinary medicine currently use a pain management model that focuses on opioids as the primary treatment for most painful conditions. In the human medical setting, opioid therapy has opened the door to potential abuse, addiction, overdose, and death, and the current public health crisis surrounding opioids has brought opioid-centered pain management into the worldwide spotlight. In 2017, the U.S. Drug Enforcement Administration began working to mitigate this crisis by implementing annual decreases in opioid production.1 These decreases primarily target full µ-agonist opioids, such as morphine, fentanyl, and hydromorphone. As of 2020, the production of some drugs, such as hydrocodone and oxycodone, had been reduced by 65% to 75%.2
Realistically, many veterinary anesthesia, surgery, and pain management cases will still require some form of opioid analgesic therapy, but veterinary medicine is moving analgesia beyond just opioids. The future of analgesia involves embracing multimodal approaches that include nonopioid drugs like N-methyl-D-aspartate (NMDA) antagonists, locoregional analgesic drugs, and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as pain scoring systems to evaluate true analgesic need and effectiveness.
Analgesia Absence of pain in response to normally painful stimuli
Analgesic An agent or drug that causes or allows for relief from pain (“painkiller”)
Central sensitization (wind-up pain) Changes in the central nervous system that occur as a result of repeated or chronic painful stimulus
Hyperalgesia An increased response to a normally painful stimulus
Nociception The activity produced in the nervous system by noxious stimuli
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage; the perception of nociception
aMuir WW III, Wiese AJ, Wittum TE. Prevalence and characteristics of pain in dogs and cats examined as outpatients at a veterinary teaching hospital. JAVMA. 2004;224(9):1459-1463. doi:10.2460/javma.2004.224.1459
The Pain Pathway
To create a multimodal analgesia plan, it is necessary to understand the pain process and the tools to best target it. Pain is complex and multifactorial, and poorly managed pain has many sequelae: impaired healing, infection, hyperalgesia, and changes to the central nervous system (CNS).3 A pain score should be part of every temperature, pulse, and respiration assessment (see Pain Scoring sidebar).
The American Animal Hospital Association pain management guide for cats and dogs states, “It is now well established that animals and humans have similar neural pathways for the development, conduction, and modulation of pain. According to the principle of analogy, because cats and dogs have neural pathways and neurotransmitters that are similar, if not identical, to those of humans, it is highly likely that animals experience pain similarly.”1
It is beyond the scope of this article to cover pain scoring systems, but many resources exist regarding pain scoring systems for canine, feline, and exotic animal patients. Additional resources for pain scoring systems and pain management guidelines are listed in Recommended Reading.
Reference
- Gruen ME, Lascelles BDX, Colleran E, et al. 2022 AAHA pain management guidelines for dogs and cats. JAAHA. 2022;58(2):55-76. doi:10.5326/JAAHA-MS-7292
The “pain pathway” is a figurative representation of the course noxious stimuli take from the moment of inception to the point of comprehension. It is divided into 4 parts: transduction, transmission, modulation, and perception (BOX 1).
- Transduction Process by which a painful stimulus is converted into a signal that will be carried to the brain
- Transmission Relay of the converted painful stimulus through afferent pain fibers
- Modulation Changes or adaptations in pain signals through mechanoreceptors
- Perception Electrical impulses are received in the brain and recognized as pain
Analgesics work to modify, downregulate, or eliminate painful stimuli felt and transmitted throughout the pain pathway. Different analgesic drugs work on different parts of the pathway. Individual drugs may work on multiple parts, but no single drug covers the entire pathway (TABLE 1). Multimodal analgesia uses multiple drugs at lower doses to cover all parts of the pain pathway.6
Opioids: The “Old” Gold Standard
Opioids are considered the gold standard in pain management because they interact with 3 of the 4 areas of the pain pathway: transduction, modulation, and perception. Many nonopioid analgesics also work in 2 or 3 of those areas; therefore, opioids do not have to be the only analgesic tool. The addition of nonopioid analgesics to a pain management protocol can reduce or eliminate the need for opioids in some situations.
Opioids are described based on their effects on µ receptors and κ receptors (TABLE 2). The µ receptors are located throughout the CNS and gastrointestinal (GI) tract. These receptors are responsible for central interpretation of pain. Pure opioid agonists (often referred to as “µ opioids” because they activate the µ receptors most strongly) provide moderate to heavy analgesia and are appropriate for many situations. While they do cause dose-dependent respiratory depression, true respiratory depression associated with µ opioids typically only occurs with very high doses. The κ receptors are located throughout the brain, spinal cord, and peripheral sensory neurons. Agonist–antagonist opioids or partial agonist opioids (sometimes referred to as “κ opioids”) provide mild to moderate analgesia. Unlike pure opioid agonists, agonist–antagonist opioids tend to cause minimal respiratory depression, minimal physical dependence, and only some dysphoric effects.
Opioids are commonly administered as a systemic injection for preoperative, postoperative, or chronic pain states. They can be delivered as part of a locoregional block or constant-rate infusion (CRI). These applications allow for titration and decrease in overall usage. Opioids are associated with side effects (BOX 2); however, these effects serve as a reason to use opioids with caution and are not a contraindication to using opioid analgesic therapy as warranted.7
- Constipation
- Decreased gastrointestinal motility
- Defecation
- Dysphoria
- Euphoria
- Hyperthermia (particularly cats)
- Hypothermia
Multimodal Analgesia
Multimodal analgesia is the concept of combining lower doses of analgesic drugs to better cover more parts of the pain pathway. Lower dosing often results in fewer side effects, and drug combinations offer more comprehensive analgesia.
A combination of NSAIDs; anticonvulsants (specifically gabapentin); locoregional anesthetic blocks; and CRIs including NMDA antagonists, α2 agonists, and sodium-channel blockers can provide effective multimodal analgesia.
Regardless of the drugs being used, it is important to be familiar with their benefits and drawbacks. When working with a less familiar drug or protocol, consider cautious dosing and extra vigilance.
NSAIDs
NSAIDs include carprofen, etodolac, meloxicam, ketoprofen, deracoxib, robenacoxib, tepoxalin, and acetylsalicylic acid (aspirin). The appropriateness of each agent depends on the species being treated. Cats, in particular, are limited to robenacoxib and meloxicam, while a wider variety of agents can be used in dogs.
NSAIDs act to mediate inflammation and work well as part of a multimodal plan addressing mild to severe pain. They can be a beneficial addition to many analgesic plans in patients without GI or renal insufficiency. NSAIDs are long acting, inexpensive, and readily available. Studies in human medicine have demonstrated that the addition of NSAIDs to analgesic protocols led to quicker inpatient discharge.8 There is also evidence of a decrease in postoperative nausea and vomiting with NSAID use, likely a result of decreased opioid administration.8
NMDA Receptor Antagonists
Ketamine, gabapentin, and amantadine work at NMDA receptor sites and have applications in treating neuropathic pain. Ketamine can be added to many parts of an anesthetic plan: premedication, induction, and intraoperative CRI. Ketamine has been shown to be useful in mediating wind-up pain, hyperalgesia, and chronic pain.
Gabapentin is an anticonvulsant used in veterinary medicine to treat chronic and neuropathic pain. Use of gabapentin has expanded to include treatment of pain and anxiety, though studies show mixed results in various species.9 The mechanism of action is not well understood, but it is thought to inhibit or decrease the release of certain neurotransmitters. Gabapentin is readily available and generally considered safe but may cause sedation. It is currently not a controlled drug federally, although this status may change.
Amantadine is an antiviral drug originally used to treat dyskinesia associated with Parkinson’s disease. It is an NMDA antagonist and dopamine agonist, working as an adjunctive medication. Often synergistic with opioids, NSAIDs, and gabapentin, this medication tends to be an “add-on” for well-managed pain or pain that is increasing despite an analgesic regimen. Amantadine is often used in oncology patients or those with unmanageable orthopedic pain.9
Local and Regional Analgesia
Locoregional anesthesia comes in many forms: epidurals, brachial plexus blocks, paravertebral blocks, incisional blocks, ring blocks, and line blocks, to name a few. Local anesthetics are a remarkable class of drugs that completely inhibit the transmission of the pain signal, thus preventing perception of the stimulus. Through this mechanism, local anesthetics can provide intense analgesia.4
In human medicine, locoregional analgesic techniques are used in many surgical procedures. The addition of these techniques has been shown to decrease persistent postoperative pain compared with cases not using locoregional blocks.10 This effect has also been demonstrated in veterinary medicine: A study reviewing pain scores of 26 dogs randomly assigned to 2 groups undergoing thoracotomy (one receiving only buprenorphine, the other receiving a bupivacaine intercostal block) found pain scores were demonstrably lower in those receiving local nerve blocks.4
Primary concerns with local anesthetics are related to toxicity. This situation arises most commonly with incorrect drug calculations or rapid IV boluses of the drug. It is essential to carefully calculate the local anesthetic dose, taking into account any other doses that may have been given. This specifically highlights the need for good communication between services. If the anesthesia service is doing an epidural with a local agent and the surgical team uses a local anesthetic for closure, it will be necessary to determine total drug doses to prevent accidental overdose. To prevent accidental intravenous administration, best practice dictates aspirating the syringe to confirm absence of blood in the needle.
Local anesthetic duration can be 2 to 72 hours, depending on the chosen agent (TABLE 3).5 Once the local anesthetic wears off, rebound pain can be significant; therefore, these drugs should be part of a multimodal approach. It is also good practice to score pain during the postoperative phase to establish a baseline and catch potential rebound effect immediately.
Local blocks are highly versatile and can be used in many situations and across species. Some examples are illustrated in FIGURES 1 THROUGH 4.
Constant-Rate Infusions
CRIs are both inhalant and opioid sparing. Lidocaine, ketamine, and dexmedetomidine are used as CRIs perioperatively and into the postoperative period (TABLE 4). Each provides adjunctive analgesia, working synergistically within the multimodal plan.
Lidocaine works in part by blocking sodium ion channels. It can reduce the amount of opioids and inhalant needed for anesthesia. Lidocaine is inexpensive and has antiarrhythmic and anti-inflammatory properties. It may be useful in cases involving visceral pain or GI motility (FIGURE 5). However, cats have increased myocardial sensitivity to local anesthetics; therefore, it is not recommended to use lidocaine infusions in cats.

Figure 5. Rabbit receiving a lidocaine constant-rate infusion after laparotomy to manage gastrointestinal pain and encourage gastric motility.
Ketamine works by antagonizing the NMDA receptors responsible for central sensitization, hypersensitization, and wind-up pain. Ketamine may not provide complete analgesia on its own, but when used as part of a multimodal approach, it can lower anesthetic and opioid requirements (FIGURE 6).

Figure 6A. Cat prepared for perineal urethrostomy procedure. The patient was extremely painful and received a morphine–bupivacaine epidural and a ketamine constant-rate infusion.

Figure 6B. Image of monitor for same patient showing vital parameters indicating comfort with the multimodal plan.
Dexmedetomidine has analgesic, anxiolytic, and sedative properties. It works by simulating α2 receptors in the CNS. Dexmedetomidine CRIs are commonly used intraoperatively to reduce minimum alveolar concentration of inhalant agents. Dexmedetomidine can be added as a postoperative CRI or used in microdoses to decrease stress and anxiety in recovering patients.11
Postoperative Care
Postoperative nursing care is often minimized in discussions of pain management, but its importance cannot be overemphasized. Patients that are kept clean and comfortable appear to need less opioid-assisted pain control. Nursing care includes timely medication administration, bladder management, bandage care, eye lubrication, position rotation, and patient interaction.12 Other considerations include easy access to food and water, as well as managing nutritional considerations. While more difficult to quantify, basic compassionate care such as grooming, stroking, and individual interaction can go a long way toward improving patient morale.
- Burns K. Veterinary practices can implement various tools to assess pain in cats and dogs. JAVMA News. March 11, 2020. avma.org/javma-news/2020-04-01/pain-points
- Grubb T, Lobprise H. Local and regional anaesthesia in dogs and cats: overview of concepts and drugs, part 1. Vet Med Sci. 2020;6(2):209-217. doi:10.1002/vms3.219
- Grubb T, Lobprise H. Local and regional anaesthesia in dogs and cats: descriptions of specific local and regional techniques, part 2. Vet Med Sci. 2020;6(2):218-234. doi:10.1002/vms3.218
- Gruen ME, Lascelles BDX, Colleran E, et al. 2022 AAHA pain management guidelines for dogs and cats. JAAHA. 2022;58(2):55-76. doi:10.5326/JAAHA-MS-7292
- International Veterinary Academy of Pain Management ivapm.org
- Mathews K, Kronen PW, Lascelles D, et al. Guidelines for recognition, assessment and treatment of pain. J Small Anim Pract. 2014;55(6):E10-E68. doi:10.1111/jsap.12200
References
- United States Drug Enforcement Administration. Justice Department, DEA propose significant opioid manufacturing reduction in 2019. August 16, 2018. Accessed January 2023. https://www.dea.gov/press-releases/2018/08/16/justice-department-dea-propose-significant-opioid-manufacturing-reduction
- Established aggregate production quotas for Schedule I and II controlled substances and assessment of annual needs for the List I chemicals ephedrine, pseudoephedrine, and phenylpropanolamine for 2023. Fed Regist. 2022;87(231):74168-74175. Accessed January 2023. https://www.govinfo.gov/content/pkg/FR-2022-12-02/pdf/2022-26351.pdf
- Gruen ME, Lascelles BDX, Colleran E, et al. 2022 AAHA pain management guidelines for dogs and cats. JAAHA. 2022;58(2):55-76. doi:10.5326/JAAHA-MS-7292
- Grubb T, Lobprise H. Local and regional anaesthesia in dogs and cats: overview of concepts and drugs, part 1. Vet Med Sci. 2020;6(2):209-217. doi:10.1002/vms3.219
- Grubb T, Lobprise H. Local and regional anaesthesia in dogs and cats: descriptions of specific local and regional techniques, part 2. Vet Med Sci. 2020;6(2):218-234. doi:10.1002/vms3.218
- Mathews K, Kronen PW, Lascelles D, et al. Guidelines for recognition, assessment and treatment of pain. J Small Anim Pract. 2014:55(6):E10-E68. doi:10.1111/jsap.12200
- Simon BT, Steagall PV. The present and future of opioid analgesics in small animal practice. J Vet Pharmacol Ther. 2017;40(4):315-326. doi:10.1111/jvp.12377
- Martinez L, Ekman E, Nakhla N. Perioperative opioid-sparing strategies: utility of conventional NSAIDs in adults. Clin Ther. 2019;41(12):2612-2628. doi:10.1016/j.clinthera.2019.10.002
- Fan TM. Pain management in veterinary patients with cancer. Vet Clin North Am Small Anim Pract. 2014;44(5):989-1001. doi:10.1016/j.cvsm.2014.05.005
- Levene JL, Weinstein EJ, Cohen MS, et al. Local anesthetics and regional anesthesia versus conventional analgesia for preventing persistent postoperative pain in adults and children: a Cochrane systematic review and meta-analysis update. J Clin Anesth. 2019;55:116-127. doi:10.1016/j.jclinane.2018.12.043
- Gutierrez-Blanco E, Victoria-Mora JM, Ibancovichi-Camarillo JA, 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. 2015;42(3):309-318. doi:10.1111/vaa.12215
- American College of Veterinary Anesthesia and Analgesia. Opioid-sparing pain therapy in animals: working task force. November 1, 2018. Accessed January 2023. https://acvaa.org/wp-content/uploads/2019/03/Opiod_Sparing_Pain_Therapy_in_Animals_Working_Task_Force_Document.pdf