Pain management for oral surgery in dogs and cats

Oral surgery in canine and feline patients often requires extended periods of anesthesia necessitating optimal anesthetic management. A safe and effective mode of pain management for the oral-surgery patient is intravenous continuous-rate infusion (CRI), using a multimodal approach to affect various levels of the nociceptive pathway.

The administration of opiates in various veterinary species has been shown to be safe and effective in decreasing MAC. Lidocaine acts to decrease central hypersensitivity in significant pain states and when given with opiates has a sparing effect on those agents. In a recent study, dogs undergoing limb amputation that received ketamine infusions had significantly lower pain scores 12 and 18 hours after surgery and were significantly more active on postoperative day three than dogs that did not. Furthermore the combination of morphine, lidocaine and ketamine delivered as a low-dose CRI provides significant decreases in required isoflurane MAC in dogs. No adverse hemodynamic effects were experienced. Medetomidine has been used as a CRI in veterinary patients; however, a recent study warned of adverse hemodynamic effects of this drug when used in this manner, noting that further investigation needs to be done before its use is advocated.

Table 1: IV Fluid Bag Based CRI Infusions

Detailed spreadsheets are available for calculation of rates, volumes and loading doses for CRI in dogs and cats using morphine, lidocaine and ketamine (Tables 1 and 2). Weight/volume calculations for commonly used analgesics are particularly convenient resources and can be found at the Veterinary Anesthesia Support Group Web site (www.vasg.org.)

Table 2: Sample CRI protocol and nerve-block calculation for a feline patient undergoing four quadrant extractions

Chronic pain

The pathophysiology of chronic pain involves the complex mechanisms of peripheral and central sensitization. Significant pain states arise frequently in oral disease because the pathology is hidden from casual owner observation. Many patients suffering chronic pain do not become anorectic. Feline lymphocytic plasmacytic gingivostomatitis (LPGS), canine stomatitis, chronic ulcerative paradental stomatitis (CUPS), untreated oral trauma and some types of oral cancer are common examples of chronic oral pain.

In the presence of persistent central and peripheral sensitization, traditional perioperative and postoperative pain management fall considerably short of the desired outcome. In order to effectively manage postoperative pain in chronic conditions, more aggressive means must be employed. A novel approach to managing chronic pain states termed the "analgesic reverse-pyramid" protocol shows considerable promise in effectively managing these patients. With this approach, immediate intense multimodal analgesic management is employed, using agents targeted to different portions of the nociceptive pathway. The chronic pain is targeted aggressively from the initiation of pain management and then tapered as desired based upon patient observation. This is in contrast to the traditional approach of adding analgesics from different classes if the initial response was less than desired.

Feline patients with LPGS particularly suffer pain. Using multimodal, pre-emptive and analgesic reverse-pyramid concepts, the author initiates pain management for these patients 6-24 hours prior to initiation of the surgical stimulus for caudal mouth extractions. Meloxicam is instituted to minimize the inflammatory peripheral sensitization experienced in these patients. Loading doses and a subsequent CRI of ketamine and morphine are commonly employed. Hydromorphone and fentanyl are alternative opioids that are particularly effective as well.

CRI is continued in the intraoperative and postoperative period. Postoperative analgesics consisting of buprenorphine (transmucosal or transdermal) or a fentanyl transdermal patch and meloxicam are continued for up to four days. If a fentanyl patch is used, it is placed such that the onset of therapeutic serum levels coincides with the anticipated culmination of the procedure. Regional nerve blocks are always employed preoperatively following achievement of a surgical plane of anesthesia. Table 1 provides an example of CRI protocol and regional nerve-block calculations for a feline patient undergoing four quadrant extractions.

Lidocaine as an additional CRI agent can be used in canine patients in the sample protocol from Table 1. A loading dose of 1.0 mg/kg IV is administered; 12.5 ml of lidocaine 2% is added to the morphinec/ketamine CRI mixture previously described and is administered at the recommended rate of 2 ml/kg/hour. Lidocaine is light-sensitive. Due to the narrow spectrum between therapeutic and toxic doses of lidocaine in feline patients (in addition to its routine inclusion in the regional nerve block), lidocaine cannot be advocated as a CRI agent for oral surgery in this species.

Chronic pain may not always be eliminated by surgical means. Many cases of oral neoplasia remain undetected until feasible surgical margins for complete resection no longer exist.

Management of patients with oral cancer involves a thorough historical and clinical evaluation using knowledge of pain behaviors and incorporation of pain scoring. Excellent descriptions of pain evaluation in companion animals have been published.

Cancer pain

Pain from oral cancer is a distinct subset of chronic pain that characteristically is very difficult to manage. Understanding the pathophysiology of cancer pain has led to research that has produced analgesics that target specific mechanisms involved in this category of painful conditions. We should familiarize ourselves with these mechanisms so that we may better choose analgesics based on pain severity, cancer location and individual patient response.

Compounds produced by tumor cells work in concert with our own macrophages, neutrophils and T-lymphocytes to increase the exitability of nociceptors. Compounds commonly secreted by tumors include prostaglandins, endothelins, interleukins and tumor necrosis-factor alpha. The management of cancer pain involves the use of analgesic agents to block the actions of these substances.

Cox-2 enzyme expression and prostaglandin production are characteristics of many tumors and the macrophages associated with them. Cox-2 expression appears to play a role in angiogenesis that in turn promotes the growth of cancer. Cox-2 inhibitors therefore may not only control inflammatory pain in this instance but also may act to alter cancer growth. Endothelins are peptides possessing properties that block angiogenesis and tumor proliferation. Plasma levels of endothelins have been correlated directly to the severity of pain in humans with prostate cancer. Drugs that block the production of prostaglandins and endothelin inhibitors have been approved for other disease states in humans. These drugs have promising potential for use in oral cancer pain management and to arrest development of some tumors.

Protons are released during the normal turnover of cells as tumors expand and apoptosis results. These protons consequently render the immediate tissue environment acidic. This corresponding decrease in tissue pH acts to induce bone destruction by osteoclasts. Acid-sensing ion channels (ASIC) expressed by nociceptors are stimulated within the acid environment and likely play a role in the generation of cancer pain. Some bisphosphonates and the substance osteoprotegerin that facilitate osteoclast apoptosis have been shown to decrease osteoclast-induced cancer pain. ASIC blocking agents currently under development may prove viable as analgesics in cancer pain.

Neuropathic pain occurs when sensory and sympathetic nerve fibers are exposed to proteolytic enzymes produced by tumor cells. Neuropathic pain is very difficult to treat in human medicine and is regarded as the most severe form of pain. Gabapentin, classically used as an anticonvulsant, is used to treat neuropathic pain and may show promise in treating pain from oral and other cancers.

Cancer pain-physiology research suggests that central sensitization (windup) plays a role in the severity and maintenance of cancer pain. Ketamine is an NMDA antagonist that is being used to successfully manage human cancer pain. Studies show that two oral NMDA- receptor antagonists, dextromethorphan and amantidine, are successful at treating human cancer pain.

Knowledge of the pathophysiology of chronic and cancer pain helps clinicians choose proper protocols for patients based on variables involved with individual case management. Pain-management studies using companion-animal models are scarce. Fortunately organizations like the Veterinary Anesthesia Support Group and International Veterinary Academy of Pain Management have developed techniques and protocols using available studies and practical experience to help clinicians better manage chronic and cancer pain in our veterinary patients. We must challenge ourselves to remain current with advances in pain management in order to continually provide comfort to our patients with chronic and oral-cancer pain.

Suggested Reading

• Lascelles BD. Interaction of Pain and Cancer, and Principles of Alleviation of Cancer Pain in Dogs and Cats. 21st Annual ACVIM Forum, 2003.

• Stein B, Thompson D. Veterinary Anesthesia Support Group. www.vasg.org (accessed Feb. 11, 2006).

• International Veterinary Academy of Pain Management www.cvmbs.colostate.edu/ivapm (accessed Feb. 11, 2006).

• Ilkiw JE, Pascoe PJ, Tripp LD. Effects of morphine, butorphanol, buprenorphine and U50488H on the minimum alveolar concentration of isoflurane in cats. Am J Vet Res. 2002; 63(8):1198-202.

• Criado AB, Gomez e Segura IA et al. Reduction of isoflurane MAC by fentanyl or remifentanil in rats. Vet Anaesth Analg. 2003; 30(4): 250-6.

• Criado AV, Gomez de Segura IA et al. Reduction of isoflurane MAC with buprenorphine and morphine in rats. Lab Anim. 2000; 34(3): 252-9.

• Koppert W, Weigand M, et al. Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg. 2004; 98(4):1050-5.

• Wagner AE, Walton JA et al. Use of low doses of ketamine administered by constant-rate infusion as an adjunct for postoperative analgesia in dogs. J Am Vet Med Assoc 2002; 221(1):72-5.

• Muir WW, Wiese AJ, March PA. Effects of morphine, lidocaine, ketamine and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane. Am J Vet Res 2003; 64(9):1155-60.

• Grimm KA, Tranquilli WJ. Cardiopulmonary effects of fentanyl in conscious dogs and dogs sedated with a continuous-rate infusion of medetomidine. Am J Vet Res 2005; 66(7):1222-6.

• Muir WM 3rd, Gaynor JS. Pain Behaviors. In: Gaynor JS, Muir W W. Handbook of Veterinary Pain Management. St. Louis: Mosby, 2002; 65-81.

• Hellyer PW. Objective, Categoric Methods for Assessing Pain and Analgesia. In: Gaynor JS, Muir W W. Handbook of Veterinary Pain Management. St. Louis: Mosby, 2002; 82-107.

Mantyh PW. Cancer Pain: Causes, Consequences and Therapeutic Opportunities. In: McMahon SB, Koltzenburg M, eds. Wall and Melzack's Textbook of Pain, 5th ed. China: Elsevier, 2006; 1087-1097.

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Weinbroum AA, Bender B et al. Preoperative and postoperative dextromethorphan provides sustained reduction in postoperative pain and patient-controlled epidural analgesia requirement: a randomized, placebo-controlled, double-blind study in lower-body bone malignancy-operated patients. Cancer 2003; 97(9): 2334-40.

Weinbroum AA, Gorodetzky A, et al. Dextromethorphan for the reduction of immediate and late postoperative pain and morphine consumption in orthopedic oncology patients: a randomized, placebo-controlled, double-blind study. Cancer 2002; 95(5): 1164-70.

Pud D, Eisenberg E, et al. The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain 1998; 75(2-3): 349-54.

Dr. Beckman practices referral dentistry at Affiliated Veterinary Specialists, Orlando, Fla.; Noah's Animal Hospitals in Indianapolis; and at Florida Veterinary Dentistry and Oral Surgery in Punta Gorda, Fla. He is president of the American Veterinary Dental Society and frequently lectures on veterinary dentistry.