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.
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
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.
- 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.
http://www.VASG.org/ (accessed Feb. 11, 2006).
- International Veterinary Academy of Pain Management
http://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.