HOW-TO SESSION: FIELD ANESTHESIA AND PAIN MANAGEMENT
stanoid thromboxane-A2.6 Gabapentin has been used as part of a multimodal analgesic protocol and was shown to help in the pain management of two horses with presumptive diagnosis of neuropathic pain.14,15
in off-loading frequency in analgesic-naive horses with pain caused by chronic laminitis.6 In this same study, ketamine administered intravenously for the first 3 days of treatment significantly im- proved off-loading frequency and forelimb load dur- ing (7 of 7 days) and after (3 days) tramadol therapy. Tramadol and ketamine had a modulatory role in the plasma levels of the pro-inflammatory cytokine tumor necrosis factor-and the vasoconstrictor pro-
4. Discussion
Laminitis pain is associated with increased off-load- ing frequency, decreased forelimb load, and other behavioral and cellular changes congruent with pathologic pain states characterized by hyperalgesia and allodynia.6,11 Pain relief with tramadol results from complex interactions with opioid, adrenergic, and serotonin receptor systems16–18 and possibly through modulation of inflammatory mediators such as pro-inflammatory cytokines and prostanoids.10,19 In analgesic-naive horses with chronic laminitis, co- administration of tramadol and ketamine resulted in significant improvement in off-loading frequency, forelimb load, and plasma levels of a major pro- inflammatory cytokine and a critical vasoconstrictor prostanoid.3 It is possible that co-administration of tramadol with NSAIDs could result in greater mod- ulation of inflammatory responses and superior pain management than when each drug is used alone. Ischemia and inflammation in the early stages of laminitis probably cause neuronal injury that even- tually shifts the acute inflammatory pain into a chronic syndrome with a prominent neuropathic component. The precise timing and nature of these events are not precisely known, but it may be estab- lished in as early as a few days. The neuropathic pain component in laminitic horses is not well re- sponsive to NSAIDs and opioids but typically re- sponds to modulators of N-methyl-D-aspartate receptors (ie, ketamine) and voltage-gated calcium channels (gabapentin) in nociceptive neurons in the spinal cord and brain.13 The beneficial effects of these drugs have been demonstrated in horses with apparent neuropathic pain.6,14,15 The equine prac- titioner should consider introducing these therapeu- tic modalities as soon as it is perceived that the current standard of care is not producing the desired pain control. The use of NSAIDs, tramadol, ket- amine, and/or gabapentin appears to be a sound
mechanistic-based approach in providing multi- modal pain management in horses with laminitis.
References
1. Hood DM. The pathophysiology of developmental and acute laminitis. Vet Clin North Am Equine Pract 1999;15:321– 343.
2. Hood DM, Grosenbaugh DA, Mostafa MB, et al. The role of vascular mechanisms in the development of acute equine laminitis. J Vet Intern Med 1993;7:228–234.
3. Parks A, O’Grady SE. Chronic laminitis: current treat- ment strategies. Vet Clin North Am Equine Pract 2003;19: 393–416.
4. Collins SN, Pollitt C, Wylie CE, et al. Laminitic pain: parallels with pain states in humans and other species. Vet 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 Equine Pract 2010;26:115–124.
6. Guedes AG, Matthews NS, Hood DM. Effect of ketamine hydrochloride on the analgesic effects of tramadol hydrochlo- ride in horses with signs of chronic laminitis-associated pain. Am J Vet Res 2012;73:610–619.
7. Buccellati C, Sala A, Ballerio R, et al. Tramadol anti-in- flammatory activity is not related to a direct inhibitory action on prostaglandin endoperoxide synthases. Eur J Pain 2000; 4:413–415.
8. Cherny NI. The treatment of neuropathic pain: from hu- bris to humility. Pain 2007;132:225–226.
9. Dworkin RH, O’Connor AB, Backonja M, et al. Pharmaco- logic management of neuropathic pain: evidence-based rec- ommendations. Pain 2007;132:237–251.
10. Kraychete DC, Sakata RK, Issy AM, et al. Proinflammatory cytokines in patients with neuropathic pain treated with Tramadol. Rev Bras Anestesiol 2009;59:297–303.
11. Jones E, Vinuela-Fernandez I, Eager RA, et al. Neuropathic changes in equine laminitis pain. Pain 2007;132:321–331.
12. Treiber K, Carter R, Gay L, et al. Inflammatory and redox status of ponies with a history of pasture-associated lamini- tis. Vet Immunol Immunopathol 2009;129:216–220.
13. Driessen B, Bauquier SH, Zarucco L. Neuropathic pain management in chronic laminitis. Vet Clin North Am Equine Pract 2010;26:315–337.
14. Dutton DW, Lashnits KJ, Wegner K. Managing severe hoof pain in a horse using multimodal analgesia and a modified composite pain score. Equine Vet Educ 2009;21:37–43.
15. Davis JL, Posner LP, Elce Y. Gabapentin for the treatment of neuropathic pain in a pregnant horse. J Am Vet Med Assoc 2007;231:755–758.
16. Driessen B, Reimann W. Interaction of the central analge- sic, tramadol, with the uptake and release of 5-hydroxytryp- tamine in the rat brain in vitro. Br J Pharmacol 1992;105: 147–151.
17. Driessen B, Reimann W, Giertz H. Effects of the central analgesic tramadol on the uptake and release of noradrena- line and dopamine in vitro. Br J Pharmacol 1993;108:806– 811.
18. Raffa RB, Friderichs E, Reimann W, et al. Opioid and non- opioid components independently contribute to the mecha- nism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992;260:275–285.
19. Bianchi M, Martucci C, Ferrario P, et al. Increased tumor necrosis factor-alpha and prostaglandin E2 concentrations in the cerebrospinal fluid of rats with inflammatory hyperalge- sia: the effects of analgesic drugs. Anesth Analg 2007;104: 949–954.
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