The Role of Gabapentin as an Analgesic: Potential Applications in Zoological Medicine
Michael J. Adkesson, DVM
Saint Louis Zoological Park, St. Louis, MO, USA; College of Veterinary Medicine, University of Missouri, Columbia, MO, USA
Originally developed as an anticonvulsant agent, gabapentin has recently become an attractive analgesic in the human medical field for the treatment of neuropathic and chronic pain. Although experience is limited, the drug has also shown promise in veterinary medicine. Gabapentin is a gamma-aminobutyric acid (GABA)-mimetic compound, although the drug has no direct GABAergic action and does not block GABA uptake or metabolism.8 The drug’s exact mechanism of action for both the anti-convulsant and analgesic properties is unknown. Research into antagonism of neuromuscular depolarizing agent receptors and blockage of calcium channels has shown the most supporting evidence for potential mechanisms of action. Evidence exists that the drug may exert effects both within the CNS and at peripheral sites.8
Gabapentin is available only as an oral preparation (Neurontin®, 100–800 mg tablets and 50 mg/ml oral solution, Parke-Davis, Pfizer, New York, New York 10017 USA). Bioavailability varies inversely with dose, with peak plasma levels obtained 3–3.2 hours after ingestion in humans.8 The drug is excreted unchanged in the urine with an elimination half-life between 4.8–8.7 hours in humans.8 Renal impairment will decrease clearance of the drug and dosages should be adjusted accordingly. Gabapentin appears to lack clinically significant drug interactions, although drugs that decrease renal glomerular filtration rate should be used with caution and certain gastrointestinal medications may interfere with absorption. Adverse effects reported in humans are minor, with somnolence, dizziness, ataxia, nausea, and fatigue being most commonly reported.8,9 Reports of massive overdoses have been documented without serious toxicity.8
Evidence from the human medical literature supports the use of gabapentin for a variety of neuropathic and chronic pain conditions. The drug is labeled for use in controlling postherpetic neuralgia (PHN) in people. Randomized, double-blind, placebo-controlled, multicenter studies have demonstrated a significant reduction in weekly mean pain scores in patients with chronic PHN pain and diabetic peripheral neuropathy when placed on doses of gabapentin titrated to maximum doses of up to 3600 mg/day.1,9 Additional studies in humans have supported the use of the medication for the treatment of neuropathic pain related to trigeminal neuralgia, multiple sclerosis, neuropathic pain in malignancy, spinal cord injury, and complex regional pain syndrome (CRPS).8 The drug has been used safely in combination with other analgesics in humans. Humans treated with a gabapentin-morphine combination were found to have more effective neuropathic pain control than with either agent alone.2
The use of gabapentin in veterinary medicine is largely extrapolated from human literature and research studies conducted in animal models. The drug has been used in anti-epileptic protocols and empirically in pain management. No studies specifically investigating the drug in a veterinary setting have been performed. However, numerous favorable anecdotal reports exist for dogs and cats with no documented major complications.4,7 In dogs, initial dosages ranging from 3 mg/kg/day to 5 mg/kg TID have been described.3,4,6 In cats, dosages of 2–10 mg/kg/day have been reported.5
In a zoological setting, gabapentin may prove useful in a variety of cases where other therapy is impractical. Animals with chronic pain that has become refractory to current analgesic therapies may benefit from the addition of gabapentin to their treatment protocols. Animals likely to suffer detrimental side-effects associated with the long-term use of other analgesics also present ideal cases for the use of gabapentin. The drug lacks significant sedative effects, which can make gabapentin an attractive option over other analgesic classes if it is effective. Gabapentin has been incorporated into analgesic treatment of several animals at the Saint Louis Zoo. Objective data on efficacy and safety is not available, but subjective success has been observed. The following cases are supplied as illustrations of potential applications.
An 18-year-old, male lion (Panthera leo) was diagnosed with mild arthritis and presumed intervertebral disk disease based on radiographically visible collapse of three thoracic disk spaces. The animal had become increasingly reluctant to move and had developed pressure sores as a result. Previous treatment consisting of etodolac and glucosamine was ineffective. Borderline renal insufficiency precluded increased NSAID doses due to potential nephrotoxicity. The animal was placed on gabapentin (3.7 mg/kg PO every 24 h) in combination with the previous analgesics. Over the next several weeks, there was subjective improvement in the animal’s mobility and activity. The pressure sores also resolved within a few weeks, providing additional subjective support that the animal was more active and comfortable.
A 44-year-old, male orangutan (Pongo pygmaeus abelii) with chronic osteoarthritis and diffuse idiopathic skeletal hyperostosis (DISH) affecting multiple joints and the spine had become refractory to treatment with celecoxib, tramadol, and glucosamine. NSAID-induced gastric ulcers had also become a problem, necessitating alternate analgesic treatments. The animal was placed on increasing doses of gabapentin (maximum dose of 4.2 mg/kg PO BID) in addition to the celecoxib and glucosamine. Over the next several days, animal management staff viewed subjective improvement in the animal’s comfort, mobility, and activity.
The apparent lack of significant drug interactions and favorable safety margin make gabapentin a potential analgesic option in a wide variety of settings. The ability to incorporate the drug into existing analgesic protocols makes it an attractive option for multimodal treatment of pain, especially in cases where current therapy is ineffective. Additional research is warranted to demonstrate safety and efficacy, but the drug shows promise in veterinary medicine.
1. Backonja, M., A. Beydoun, K.R. Edwards, S.L. Schwartz, V. Fonseca, M. Hes, L. LaMoreaux, and E. Garofalo. 1998. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. J. Am. Med. Assoc. 280: 1831–1836.
2. Gilron, I., J.M. Bailey, D. Tu, R.R. Holden, D.F. Weaver, and R.L. Houlden. 2005. Morphine, gabapentin, or their combination for neuropathic pain. N. Engl. J. Med. 352: 1324–1334
3. Hardie, E.M., B. D. X. Lascelles, and J. S. Gaynor. 2003. Managing chronic pain in dogs: the next level. Proc Managing Pain Symp. Available at https://www.vin.com. Accessed March 29, 2006.
4. Lamont, L.A., W. J. Tranquilli, and K. A. Mathews. 2000. Adjunctive analgesic therapy. Vet. Clin. North Am. Small Anim. Prac. 30: 805–813.
5. Lascelles, B.D.X., S.A. Robertson, and J. S. Gaynor. 2003. Proc. Managing Pain Symp. Available at https://www.vin.com. Accessed March 29, 2006.
6. Pascoe, P.J. 2000. Problems of Pain Management. In: Flecknell, P.A. and A. Waterman-Pearson (eds.). Pain Management in Animals. W.B. Saunders. London. Pp. 161.
7. Robertson, S.A. 2005. Managing pain in feline patients. Vet. Clin. North Am. Small Anim. Prac. 35: 129–146.
8. Rose, M. A., and P. C. A. Kam. 2002. Gabapentin: pharmacology and its use in pain management. Anaesth. 57: 451–462.
9. Rowbotham, M., N. Harden, B. Stacey, P. Bernstein, L. Magnus-Miller. 1998. Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. J. Am. Med. Assoc. 280: 1837–1842.