Long-term use of gabapentin for musculoskeletal disease and

Journal of Feline Medicine and Surgery

15(6) 507 –512

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DOI: 10.1177/1098612X12470828

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Introduction

Gabapentin was developed originally as an antiepileptic

medication.

It has gained substantial attention for its

role in the treatment of chronic neuropathic pain in

humans.

Gabapentin binds to the N-type voltage cal-

cium channels in the dorsal root ganglion neurons.

2,3

Binding to this receptor may result in a reduction in the

release of excitatory neurotransmitters, such as gluta-

mate and substance P,

and has a modulating effect on

gamma-aminobutyric acid receptors.

An intracellular

effect leading to a delayed expression of voltage-gated

calcium channels at the cell surface resulting in a

decreased calcium influx has also been postulated.

The

antinociceptive effects seem to occur primarily after

injury and it has been described that gabapentin inter-

acts with N-methyl-D-aspartate receptors (NMDA)

involved in the development of central sensitisation.

The relative importance of various actions of gabapentin

remain to be elucidated.

Treating neuropathic pain in cats is a challenge for

veterinary surgeons. The choice of drugs available to

treat maladaptive pain disorders in cats is limited; cats

have a well-recognised limited ability to metabolise

drugs by hepatic glucuronidation and administration of

medication by the owner can be challenging.

Moreover,

to diagnose, reliably assess and score pain in these

patients is difficult.

The following three cases document

long-term analgesic management of cats sustaining mul-

tiple musculoskeletal injuries or presenting for insidious

lameness using gabapentin as part of the pain manage-

ment strategy.

Long-term use of gabapentin for

musculoskeletal disease and trauma

in three cats

Nina D Lorenz

, Eithne J Comerford

and Isabelle Iff

Abstract

Gabapentin has been widely used in human medicine to control acute and chronic pain. Although the exact

mechanism of action has yet to be determined, its use in veterinary medicine is increasing. The clinical use of

gabapentin for analgesia in cats has been reported in review articles and one case report. Managing chronic

pain, particularly in the feline patient, poses a challenge to veterinary surgeons. This report details the long-term

use of gabapentin for musculoskeletal pain or head trauma in three cats. All cats received gabapentin for several

months at an average dose of 6.5 mg/kg q12h. Clinical signs suggestive of pain, such as aggression, avoiding

human interaction and loss of appetite, were observed to decrease with the administration of gabapentin, used

as part of an analgesia regime or as sole medication. Long-term follow-up with the owners of all cats indicated

that satisfactory pain management was achieved, administration was easy and no obvious side effects during the

period of administration occurred. We conclude that long-term treatment with gabapentin is of potential benefit in

controlling pain in cases of head trauma, as well as musculoskeletal disease. It may provide a valuable adjunct for

the management of chronic pain in cats and should be investigated further for its clinical use and safety.

Accepted: 15 November 2012

Small Animal Teaching Hospital, School of Veterinary Science,

Faculty of Health and Life Sciences, University of Liverpool,

Neston, Wirral, UK

Small Animal Teaching Hospital; Institute of Ageing and Chronic

disease and School of Veterinary Science, Faculty of Health and

Life Sciences, University of Liverpool, Liverpool, UK

Veterinary Anaesthesia Services, Winterthur, Switzerland

Corresponding author:

Nina Lorenz BVSc (Hons), MACVSc, MRCVS, Small Animal

Teaching Hospital, School of Veterinary Science, Faculty of

Health and Life Sciences, University of Liverpool, Chester High

Road, Neston, Wirral, CH64 7TE, UK

Email: [email protected]

470828

JFM15610.1177/1098612X12470828Journal of Feline Medicine and SurgeryLorenz et al

2012

Case Series

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508 Journal of Feline Medicine and Surgery 15(6)

Case descriptions

Case 1

A 3-year-old female neutered domestic shorthair cat suf-

fered multiple skull fractures following a road traffic

accident. The fractures were repaired surgically, and the

right vertical mandibular ramus and articular process of

the temporomandibular joint (TMJ) were removed by

the referring veterinary surgeon. An oesophageal feed-

ing tube was placed. Upon presentation at the referral

hospital, clinical examination showed malocclusion with

lateral displacement of the right mandible. Under seda-

tion the displaced mandible could be reduced to its nor-

mal position with a normal range of motion. The cat

managed to lick and swallow liquid food and the owners

opted for conservative treatment and oesophagostomy

tube feeding at home. Pain management consisted of

meloxicam (Metacam; Boehringer Ingelheim) 0.05 mg/

kg q24h PO and buprenorphine (Vetergesic; Alstoe Ltd

for Reckitt Benckiser) 0.02 mg/kg subcutaneously (SC)

q8h while hospitalised and a feeding plan was devised.

The cat was discharged after 5 days on a continued

course of meloxicam 0.05 mg/kg q24h PO. At the reas-

sessment visit 2 weeks after the initial presentation the

cat was examined and the following tests were per-

formed: (i) food offered in the consult room — the cat

showed strong interest in eating, but appeared unable to

prehend the food; (ii) when the cat was observed in its

own cage it opened its mouth repeatedly, seemed agi-

tated and shook its head; (iii) manipulation of the man-

dible while the cat was conscious was not possible

because of avoidance behaviour when attempting to

approach the head. These observations were taken as an

indication of pain; however, a component of malocclu-

sion with an avoidance reaction caused by learned

behaviour after the accident cannot be excluded.

Changes in diet were advised and surgical intervention

was planned should the cat not improve. In addition to

the meloxicam, gabapentin 6.5 mg/kg (Nova Labora-

tories) q12h was administered through the feeding tube.

The oesophageal feeding tube had been removed by the

referring veterinary surgeon and the meloxicam discon-

tinued after about 6 weeks. Four months after discharge

the cat was doing well on continued administration of

gabapentin as the only analgesic medication provided

(Figure 1). The cat was given approximately 6.5 mg/kg

of gabapentin every q12h by sprinkling specially formu-

lated 25 mg capsules (Nova Laboratories Ltd UK) over

the food. The owner reported no further episodes of pain

and the cat was tolerating soft food, despite the presence

of a persistently displaced mandible and malocclusion.

After this, the cat was lost to follow-up.

Case 2

An 8-year-old male neutered Burmese cat was presented

with pneumothorax and multiple skull fractures follow-

ing a road traffic accident 72 h earlier. The referring vet-

erinarian provided emergency treatment, including

buprenorphine 0.02 mg/kg intravenously (IV) and an

unknown dose of dexamethasone (Dexadreson

;

Intervet). On presentation the cat had misalignment of

the right mandible to the right with crepitus.

Buprenorphine 0.02 mg/kg IV and fluid therapy was

continued overnight. A computed tomography (CT)

scan under general anaesthesia demonstrated multiple

fractures of the mandible and maxilla with small dis-

placement of the fragments and a dislocated TMJ. An

oesophageal feeding tube was placed to allow for nutri-

tional support. The mandibular symphyseal fracture

was stabilised and a tape muzzle was applied to prevent

re-luxation of the TMJ. Owing to partial occlusion of the

nasal passages by haemorrhage the tape muzzle was not

tolerated. Meloxicam (Metacam; Boehringer Ingelheim)

0.2 mg/kg IV was administered once and continued at

0.05 mg/kg q24h PO. The cat underwent surgery for

placement of an external skeletal fixator to stabilise the

mouth in a semi-open position. Perioperative analgesia

was provided using medetomidine (Domitor; Pfizer),

methadone (Physeptone; Martindale Pharmaceuticals),

meloxicam and fentanyl (Fentanyl; Martindale Pharma-

ceuticals). Post-surgical analgesia included 4-hourly

methadone 0.3 mg/kg IV q4h and meloxicam 0.05 mg/

kg q24h PO. Methadone was substituted with buprenor-

phine 0.02 mg/kg IV every 8 h after 24 h. The cat was

depressed, facing the back wall of the cage and growling

Figure 1 Chronological order and duration of administered analgesic treatment in case 1

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Lorenz et al 509

when being handled. The administration interval of

buprenorphine was changed to q6h, which resolved the

‘growling when handled’. However, the other signs peri-

odically recurred and gabapentin 6.5 mg/kg q12h was

added via the feeding tube to provide additional pain

relief. The cat improved within 24 h with changes in

demeanour, purring when being stroked and interacting

with the carer. The buprenorphine was reduced to q8h

and stopped after an additional week. The cat was dis-

charged 3 weeks after the surgery on meloxicam 0.05

mg/kg q24h and gabapentin 6.5 mg/kg dispensed as

specially formulated 25 mg capsules q12h PO, and the

owner was given instructions on how to use the feeding

tube. After 5 days inadvertent removal of the oesophago-

stomy tube at home occurred and the cat was hospital-

ised for 3 weeks. During this time analgesia was provided

using gabapentin 6.5 mg/kg every 12 h, meloxicam 0.05

mg/kg q12h via a new feeding tube and buprenorphine

0.02 mg/kg SC q8h (Figure 2). After a CT scan demon-

strating adequate callus formation the external skeletal

fixator was removed. The cat showed malocclusion, but

was able to eat soft food well and the oesophageal tube

was removed. The cat was discharged on gabapentin 6.5

mg/kg q12h PO for 2 weeks. After 1 month the cat was

revaluated and, despite the malocclusion, showed no

signs of oral laceration and was able to eat soft food. The

owner reported episodes where the cat was pawing at

his mouth and seemed distressed within the last weeks;

these signs were thought to be related to intermittent

facial pain. Gabapentin was resumed at 6.5 mg/kg q12h

PO with instructions to increase the dose to 13 mg/kg

q12h PO should the signs not resolve. On further follow-

up the owner reported having administered gabapentin

6.5 mg/kg q12h PO intermittently for 2 months follow-

ing this visit.

Long-term follow-up at 40 months after initial injury

revealed the cat to be doing well without receiving any

medication. It was eating and drinking normally.

Occasional episodes of clinical signs indicative of orofa-

cial pain were observed with a lower severity and

frequency, which did not warrant continued gabapentin

therapy, according to the owner. The owner reported no

side effects and found it easy to administer gabapentin

to the cat.

Case 3

A 9-year-old domestic shorthair cat presented for

assessment of a chronic left forelimb lameness of 2

months’ duration. The lameness had been localised to

the carpal and elbow region, and was unresponsive to

meloxicam. Clinical examination at the referral hospi-

tal showed increased weight-bearing on the right fore-

limb at stance, but subjective gait analysis was hindered

by the anxious nature of the cat. Adequate muscle mass

and moderate pain of the left carpus and elbow joint

were found on palpation. Blood and urine analysis

revealed mild elevations of urea and creatinine, with a

urine specific gravity of 1.027 and normal urine pro-

tein/creatinine ratio. Radiographs performed on the

next day were indicative of left carpal joint osteoarthri-

tis, which was supported by the absence of infectious

or immune-mediated pathology on synovial fluid

analysis. Given the history of azotaemia the meloxicam

therapy was discontinued and the cat discharged the

next day on gabapentin syrup 40 mg/ml (Nova

Laboratories) at a dose of 6.5 mg/kg q12h PO for 4

weeks. A telephone update was obtained after 4 weeks

and the owners reported that the clinical signs of lame-

ness had decreased, although they were not completely

resolved. Given the positive response it was advised to

continue with gabapentin therapy for the next 4–6

weeks and then as required with further episodes of

lameness. The owners administered gabapentin syrup

(Nova Laboratories) 6.5 mg/kg q12h PO intermittently

for 12 months following discharge during episodes of

noticeable left forelimb lameness (Figure 3). The owner

administered the medication easily and the cat toler-

ated the drug well, as no obvious side effects were

noted. The cat showed no lameness 24 months follow-

ing discharge and was without medication.

Figure 2 Chronological order and duration of administered analgesic treatment in case 2. Note that during the 24 h

administration of methadone postoperatively, the buprenorphine was discontinued (depicted by the blue line on the

buprenorphine bar)

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510 Journal of Feline Medicine and Surgery 15(6)

Discussion

The purpose was to report that gabapentin may have a

role in the management of chronic pain condition in

cats associated with trauma or insidious musculoskel-

etal pain. In the small number of cases reported here,

there were no obvious side effects observed and the

owners reported no problems with administration of

the drug.

Two of the three cats received other analgesics dur-

ing the initial pain management plan, including, but

not limited to, buprenorphine and meloxicam.

Gabapentin was added at a later stage to provide addi-

tional analgesia, therefore using analgesic drugs which

act at different levels of the pain pathways. Gabapentin

was the sole analgesic administered at home for all

cases. In case three gabapentin was chosen as an alter-

native to non-steroidal anti-inflammatory drugs

(NSAIDs) owing to the presence of azotaemia. A NSAID

was administered in case two despite an unknown dose

of dexamethasone being administered within 48 h of

referral. While there is a possible concern of adminis-

tering a NSAID concurrently with a corticosteroid,

there is presently no information on the simultaneous

use of dexamethasone and meloxicam in the cat.

Nevertheless, the reader is cautioned to use these drugs

concurrently or within short succession of each other

until further data are available.

Gabapentin was administered for 5 (case 1), 3 (case 2)

and one (case 3) month(s) continuously and then inter-

mittently for a further 3, 2 and 12 months, respectively,

without clinical adverse effects. Long-term follow-up at

24–36 months by telephone interview showed that

gabapentin, both in capsule and syrup formation, was

tolerated well by all three cats. There were no obvious

side effects in any of the cats, even with administration

of the drug up to 1 year following discharge, and the

owners reported ease of administration. Although there

are currently no scientific reports on long-term efficacy

of gabapentin in cats, authors of a recent review paper

also comment on its usefulness for the treatment of neu-

ropathic pain in cats.

Gabapentin has been increasingly proposed as an anal-

gesic for treating various conditions, ranging from periop-

erative analgesia to treatment of chronic pain in humans.

3,8,9

In veterinary medicine gabapentin has been used in dogs

and cats anecdotally to treat chronic and perioperative

pain.

Gabapentin was found to be analgesic in two cats

with multiple injuries, when used as part of a multidrug

approach to pain management.

Other veterinary studies

describe the pharmacokinetics in cats

and dogs.

In a

study using a thermal threshold model, gabapentin at

doses of 5–30 mg/kg did not prove to have an acute anti-

nociceptive effect in cats.

However, this model, may not

accurately mirror clinical pain, where, commonly, a combi-

nation of inflammatory and neuropathic pain is present.

The mechanisms of pain in cases reported here were likely

a combination of inflammatory and neuropathic pain, par-

ticularly with extensive trauma.

13,14

This severe acute pain

may have contributed to an up-regulation of pain recep-

tors through central sensitisation.

Most commonly, gabapentin is recommended for use

in persistent chronic pain or neuropathic pain.

Hyperalgesia and allodynia are commonly reported fea-

tures of neuropathic and chronic pain.

It is probable

that some of the signs observed were due to allodynia,

for example, the presence of food in the mouth evoking

a painful reaction in two of the cases reported.

Assessment and diagnosis of pain in cats is chal-

lenging, as their signs of pain are different from dogs.

Pain scoring systems for cats have only recently been

validated for acute pain and chronic pain; however,

these tools were not available at the time of treatment

of the cats reported here.

16–19

Measuring heart rate, res-

piration rate, blood pressure, plasma cortisol or

β-endorphin values have been shown to not be reliable

indicators of pain in cats.

6,20

Observation of a cat’s

behaviour, as well as interaction with the cat by an

experienced veterinary surgeon, is the current stand-

ard.

This pain assessment strategy has been found

most useful in various studies looking at pain assess-

ment in cats.

20,21

Other commonly used tools to diag-

nose pain in cats include inferring from human patients

or other species with similar conditions, as well as

analgesic trials.

6,7

Robertson

states that a simple

descriptive score, visual analogue score (VAS) or

dynamic interactive VAS may be used for pain assess-

ment in cats, in addition to monitoring the response to

a test dose of analgesic, particularly if there is uncer-

tainty if the patient is truly painful. These pain assess-

ment strategies were employed successfully in case

two where the cat showed behaviours established to be

indicative of pain. These included growling when

being handled, facing the cage wall, being dull and

inappetent, and the improvement of these behaviours

Figure 3 Chronological order and duration of administered analgesic treatment in case 3

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Lorenz et al 511

with administration of gabapentin. The three cats

reported here all had conditions deemed painful in

humans or other animals, as well as observed signs

suggestive of orofacial or musculoskeletal pain (inap-

petence, inability to prehend food, pawing at the face,

lameness, dullness and staring at the cage wall). In all

cats, pain was ongoing for more than 8 days and reso-

lution or improvement of signs appeared to coincide

with the administration of gabapentin. Although there

were no validated scoring systems available at the time

of treatment of the cats reported here, we were in

agreement with the findings of other studies

6,14,21

and

felt that these assessment criteria, including the

response to analgesic therapy in all three cases offered

a good and reliable method to provide adequate anal-

gesia. In the future the use of a validated pain scoring

system would be helpful for evaluation of such ani-

mals during hospitalisation, as well as post-discharge,

using a multidimensional composite pain scale and a

numeric rating scale of different behaviours, respec-

tively.

16,22

A method incorporating scoring a number of

the observed behaviours has been described as Client

Specific Outcome Measures (CSOM) in a study on

chronic pain in dogs,

and may be also useful in scor-

ing chronic pain in cats. Unfortunately, specific owner-

based pain assessment was not systematically carried

out in these cases.

Other potential benefits of gabapentin as a long-term

analgesic include good bioavailability in cats when

given orally, with a reported 88.7% with a half-life of

2.8 h.

However, variation can occur and food was impli-

cated to influence uptake of oral gabapentin.

Cats have

a limited ability for hepatic glucuronidation and thus are

more susceptible to toxic side effects. There may also be

less active drug available if the parent drug requires

metabolising to the active compound by this pathway.

Most commonly observed adverse effects in cats

include ataxia and sedation.

None of these side effects

were observed or reported during hospitalisation or

reported by owners in any of the cases.

Oral administration of medication is another chal-

lenge in cats in general and especially so in animals with

orofacial pain. Although gabapentin was first given via

feeding tube in two of the cats, all cats eventually took

gabapentin formulated either as a powder or syrup over

the food without problems.

Conclusions

Gabapentin was shown to be of conceivable, though

unproven, benefit for analgesic management of these

cases with orofacial or musculoskeletal problems,

which were all characterised by chronic pain. No

adverse events or morbidity were observed in these

animals during the treatment period, suggesting that

gabapentin used at 6–7 mg/kg is a well-tolerated

dose, even for more extended administration. Further,

owners easily manage administration of this drug. As

such, gabapentin may be considered as a long-term

treatment for the management of chronic pain in cats.

However, more research is needed to confirm and

extend these observations, and determine the safety

of gabapentin with long-term administration.

Acknowledgements

The authors would like to acknowl-

edge the contribution of Nick Macdonald, who was involved

in the primary care of two of the reported cases, the nursing,

anaesthesia and imaging staff at the SATH, as well as the refer-

ring veterinary surgeons.

Funding This research received no specific grant from any

funding agency in the public, commercial, or not-for-profit

sectors.

Conflict of interest The authors do not have any potential

conflicts of interest to declare.

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