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How to Provide Pain Relief for Laminitis in the Field

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How to Provide Pain Relief for Laminitis in the Field HOW-TO SESSION: FIELD ANESTHESIA AND PAIN MANAGEMENT How to Provide Pain Relief for Laminitis in the Field Alonso Guedes, DVM, MS, PhD Author’s address: University of California, Davis, One Shields Avenue, Davis, CA 95616; e-mail: [email protected]. © 2013 AAEP. 1. Introduction characterized by hyperalgesia (ie, exaggerated re- sponse to a painful stimulus) and allodynia (ie, pain Laminitis is an extremely painful condition with 6,13–15 still incompletely understood pathophysiology.1–3 response to a normally nonpainful stimulus). All too often, the uncontainable severe pain associ- The goal of this report is to present techniques tar- ated with the disease is the single most common geting such pathologic pain states that can be used reason for euthanasia of laminitic horses. Treat- to manage pain and suffering in horses with ment is frequently unfinished because owners and laminitis. health providers feel forced to end the extreme pain and suffering by ending the life of the afflicted ani- 2. Recommended Agents and Routes of mal. More positive treatment results could be ob- Administration tained if pain and suffering could be successfully Tramadol tablets can be crushed into powder, mixed modulated.4 Non-steroidal anti-inflammatory with syrup or molasses, and administered orally at a drugs (NSAIDs) such as flunixin meglumine and dose of 5 mg/kg q 12 hours.6 phenylbutazone have long been and still remain the Ketamine can be administered intravenously as a primary pharmacologic agents used to treat pain constant rate infusion at a dose of 0.6 mg/kg per and inflammation in horses with laminitis.5 hour for 6 hours/day for 3 to 5 days (or longer as 6 Tramadol is emerging as an additional option to- needed) through a syringe pump, or it can be di- ward providing multimodal analgesia in equine luted in 0.9% saline and dripped by gravity. Alter- laminitis,6 and its efficacy has been well established natively, it can be administered intramuscularly at 14 in neuropathic and inflammatory pain states.7–10 0.5 mg/kg q 6 hours. Because it is now known that pain associated with Gabapentin can be administered orally at doses laminitis has both inflammatory and neuropathic ranging from 2.5 to 20 mg/kg q 8 hours, q 12 hours, 13–15 components,11,12 targeted multimodal analgesic or q 24 hours, as needed. therapies probably will be necessary for effective pain modulation. Drugs such as ketamine and ga- 3. Evidence of Efficacy bapentin may be very beneficial in modulating neu- When administered alone, tramadol was shown to ropathic pain as well as pathologic pain states produce significant initial improvement (3 of 7 days) NOTES AAEP PROCEEDINGS ր Vol. 59 ր 2013 467 HOW-TO SESSION: FIELD ANESTHESIA AND PAIN MANAGEMENT in off-loading frequency in analgesic-naive horses mechanistic-based approach in providing multi- with pain caused by chronic laminitis.6 In this modal pain management in horses with laminitis. same study, ketamine administered intravenously for the first 3 days of treatment significantly im- References proved off-loading frequency and forelimb load dur- 1. Hood DM. The pathophysiology of developmental and acute ing (7 of 7 days) and after (3 days) tramadol therapy. laminitis. Vet Clin North Am Equine Pract 1999;15:321– 343. Tramadol and ketamine had a modulatory role in 2. Hood DM, Grosenbaugh DA, Mostafa MB, et al. The role of the plasma levels of the pro-inflammatory cytokine vascular mechanisms in the development of acute equine tumor necrosis factor-␣ and the vasoconstrictor pro- laminitis. J Vet Intern Med 1993;7:228–234. stanoid thromboxane-A .6 Gabapentin has been 3. Parks A, O’Grady SE. Chronic laminitis: current treat- 2 ment strategies. Vet Clin North Am Equine Pract 2003;19: used as part of a multimodal analgesic protocol and 393–416. was shown to help in the pain management of two 4. Collins SN, Pollitt C, Wylie CE, et al. Laminitic pain: horses with presumptive diagnosis of neuropathic parallels with pain states in humans and other species. Vet pain.14,15 Clin North Am Equine Pract 2010;26:643–671. 5. Belknap JK. The pharmacologic basis for the treatment of developmental and acute laminitis. Vet Clin North Am 4. Discussion Equine Pract 2010;26:115–124. 6. Guedes AG, Matthews NS, Hood DM. Effect of ketamine Laminitis pain is associated with increased off-load- hydrochloride on the analgesic effects of tramadol hydrochlo- ing frequency, decreased forelimb load, and other ride in horses with signs of chronic laminitis-associated pain. behavioral and cellular changes congruent with Am J Vet Res 2012;73:610–619. pathologic pain states characterized by hyperalgesia 7. Buccellati C, Sala A, Ballerio R, et al. Tramadol anti-in- and allodynia.6,11 Pain relief with tramadol results flammatory activity is not related to a direct inhibitory action on prostaglandin endoperoxide synthases. Eur J Pain 2000; from complex interactions with opioid, adrenergic, 4:413–415. 16–18 and serotonin receptor systems and possibly 8. Cherny NI. The treatment of neuropathic pain: from hu- through modulation of inflammatory mediators such bris to humility. Pain 2007;132:225–226. as pro-inflammatory cytokines and prostanoids.10,19 9. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmaco- logic management of neuropathic pain: evidence-based rec- In analgesic-naive horses with chronic laminitis, co- ommendations. Pain 2007;132:237–251. administration of tramadol and ketamine resulted 10. Kraychete DC, Sakata RK, Issy AM, et al. Proinflammatory in significant improvement in off-loading frequency, cytokines in patients with neuropathic pain treated with forelimb load, and plasma levels of a major pro- Tramadol. Rev Bras Anestesiol 2009;59:297–303. inflammatory cytokine and a critical vasoconstrictor 11. Jones E, Vinuela-Fernandez I, Eager RA, et al. Neuropathic 3 changes in equine laminitis pain. Pain 2007;132:321–331. prostanoid. It is possible that co-administration of 12. Treiber K, Carter R, Gay L, et al. Inflammatory and redox tramadol with NSAIDs could result in greater mod- status of ponies with a history of pasture-associated lamini- ulation of inflammatory responses and superior pain tis. Vet Immunol Immunopathol 2009;129:216–220. management than when each drug is used alone. 13. Driessen B, Bauquier SH, Zarucco L. Neuropathic pain management in chronic laminitis. Vet Clin North Am Ischemia and inflammation in the early stages of Equine Pract 2010;26:315–337. laminitis probably cause neuronal injury that even- 14. Dutton DW, Lashnits KJ, Wegner K. Managing severe hoof tually shifts the acute inflammatory pain into a pain in a horse using multimodal analgesia and a modified chronic syndrome with a prominent neuropathic composite pain score. Equine Vet Educ 2009;21:37–43. 15. Davis JL, Posner LP, Elce Y. Gabapentin for the treatment component. The precise timing and nature of these of neuropathic pain in a pregnant horse. J Am Vet Med events are not precisely known, but it may be estab- Assoc 2007;231:755–758. lished in as early as a few days. The neuropathic 16. Driessen B, Reimann W. Interaction of the central analge- pain component in laminitic horses is not well re- sic, tramadol, with the uptake and release of 5-hydroxytryp- sponsive to NSAIDs and opioids but typically re- tamine in the rat brain in vitro. Br J Pharmacol 1992;105: 147–151. sponds to modulators of N-methyl-D-aspartate 17. Driessen B, Reimann W, Giertz H. Effects of the central receptors (ie, ketamine) and voltage-gated calcium analgesic tramadol on the uptake and release of noradrena- channels (gabapentin) in nociceptive neurons in the line and dopamine in vitro. Br J Pharmacol 1993;108:806– spinal cord and brain.13 The beneficial effects of 811. 18. Raffa RB, Friderichs E, Reimann W, et al. Opioid and non- these drugs have been demonstrated in horses with 6,14,15 opioid components independently contribute to the mecha- apparent neuropathic pain. The equine prac- nism of action of tramadol, an ‘atypical’ opioid titioner should consider introducing these therapeu- analgesic. J Pharmacol Exp Ther 1992;260:275–285. tic modalities as soon as it is perceived that the 19. Bianchi M, Martucci C, Ferrario P, et al. Increased tumor necrosis factor-alpha and prostaglandin E2 concentrations in current standard of care is not producing the desired the cerebrospinal fluid of rats with inflammatory hyperalge- pain control. The use of NSAIDs, tramadol, ket- sia: the effects of analgesic drugs. Anesth Analg 2007;104: amine, and/or gabapentin appears to be a sound 949–954. 468 2013 ր Vol. 59 ր AAEP PROCEEDINGS.
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