Vet Clin Equine 18 (2002) 47–60

Use of opioids for pain and anesthetic

management in horses
Rachel C. Bennett, BVSca,
Eugene P. Steffey, VMD, PhDb,*
a
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road,
Cambridge, CB3 0ES, UK
b
Department of Surgical and Radiological Sciences, School of Veterinary Medicine,
University of California, Davis, CA 95616, USA

Opioids have been administered clinically to horses for at least seventy

years. Results of tests of morphine and derivatives of morphine in horses
that were reported in 1937 were summarized then as ‘‘. . . analgesic action
is present with doses [of the opioids] slightly smaller than those required
to induce excitation. With these sub-excitant doses there appears almost
no evidence of sedative action. . .’’ [1]. In 1979 Tobin et al. demonstrated
that horses possessed opioid receptors within the brain and spinal cord
[2]. Recently, Hellyer and coworkers have also identified opioid receptors
in synovial membranes [3]. Horses have also been shown to produce endo-
genous opioids [4].
In species other than the horse, opioids are a frequent component of pre-,
peri-, and post-operative management of patients, because they minimize or
abolish pain. They often form part of a balanced anesthetic regime because
the analgesia they provide reduces the requirement for anesthetic drugs such
as inhalation anesthetic agents. In this way some of the undesirable side
effects of the anesthetic agents (e.g., cardiovascular depression) may be mini-
mized. Opioids have been similarly used in a wide range of species, but their
use in horses has never been as straightforward. Any usefulness is restricted
because there appears to be a very narrow margin between analgesia and
arousal or excitation. Indeed, the analgesic potency of opioids in horses is
not readily and consistently quantifiable, and there are a number of other
undesirable side effects of opioids that must be considered clinically. In this
regard, the action of opioids in horses deviates markedly from the more

* Corresponding author.
E-mail address: epsteffey@ucdavis.edu (E.P. Steffey).

0749-0739/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved.
PII: S 0 7 4 9 - 0 7 3 9 ( 0 2 ) 0 0 0 1 1 - 1
48 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60

desirable actions of depressed behavior seen in, for example, humans and
dogs. In this chapter we review objective evidence for and against routine
use of opioids in managing pain and general anesthesia in horses.

Opioids administered systemically

Analgesic actions
Evidence for an analgesic effect
A number of studies in horses have demonstrated an analgesic effect of
systemically administered opioids.
Arguably the most convincing data are those published by Kamerling
and coworkers [5,6]. In the most recent of these two reports, the hoof-
withdrawal test and the skin-twitch reflex were used as pain models to study
the effect of U50488H, an investigational, selective kappa (j)-opioid agonist.
Doses of 40, 80 and 160 lg/kg were administered IV. At a dose of 160 lg/kg
the hoof-withdrawal reflex increased 100%. This response was repeated using
the skin-twitch reflex. The locomotor response to U50488H was minimal.
Signs of sedation were dose-dependent. The analgesic effects were absent
when horses were pretreated with naloxone, implying that the response was
mediated via opiate receptors. The results of this study indicate that kappa-
receptor opioids produce analgesia with less attendant locomotor and sympa-
thetic stimulation than l-opioids.
In a report by Pippi and Lumb [7] analgesic effects of high-dose intrave-
nous fentanyl (0.22 mg/kg), meperidine (4.4 mg/kg), methadone (0.22 mg/kg),
oxymorphone (0.033 mg/kg), pentazocine (2.2 mg/kg), and the a-2 adrenergic
agonist xylazine (2.2 mg/kg) were evaluated in ponies, using models of super-
ficial, deep, and visceral pain. All drugs were initially given alone; subse-
quently, the opioids were individually administered in combination with
xylazine. Xylazine was the most consistent drug used for relief of all forms
of pain, but was significantly better than the opioids only in the relief of
deep pain. Xylazine plus fentanyl was found to be significantly better for
treatment of visceral pain, but the small number of observations, four, limits
the usefulness of these data. The authors point out that that none of the
drugs tested proved to be uniformly effective with all types of pain.
The use of opioids as both superficial and visceral analgesics was assessed
by Kalpravidh and coworkers [8,9]. In one study, the analgesic effects of IV
butorphanol (0.05, 0.1, 0.2, 0.4 mg/kg) were compared with those of IV pen-
tazocine (2.2 mg/kg) in six horses. Analgesic effects were noted following both
butorphanol (at higher doses) and pentazocine. The duration of analgesia
following butorphanol was 15–90 minutes and following pentazocine was
15–30 minutes. The highest dose of butorphanol (0.4 mg/kg) provided the
most intense and longest analgesia when compared with pentazocine. Unde-
sirable behavioral side effects (e.g., ataxia, restlessness) were noted for
varying time periods with both drugs, and both magnitude and duration of
 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60 49

these effects were again dose-related. All things considered, the authors
recommended a dose of 0.2 mg/kg butorphanol IV for analgesic purposes.
In the second study, butorphanol (0.22 mg/kg), flunixin meglumine
(2.2 mg/kg), levorphanol tartrate (0.033 mg/kg), morphine (0.66 mg/kg) and
xylazine hydrochloride (2.2 mg/kg) were administered intramuscularly to
eight ponies. Xylazine provided the greatest increase in superficial and visc-
eral pain thresholds during the first 60 minutes of the study. Morphine pro-
vided superficial analgesia at 30 minutes, whereas butorphanol provided
visceral analgesia throughout the four hour study. Interpretation of the
results of both the horse and pony studies from this laboratory (and there-
fore clinical application decisions) are confounded by the marked variation
in the animalsÕ response to the stimuli and drugs given (suggested by the
large standard error of the mean [SEM] values reported).
In another study similarly reported but in abstract form [10], 66 equine
patients with abdominal pain were treated with butorphanol (0.1 mg/kg),
IV. The analgesic response was considered excellent (pronounced analgesic
effect for a time period adequate to permit specific therapy) or good (notice-
able analgesic effect with minor indications of pain).
Johnson et al. [11] investigated the efficacy of phenylbutazone, flunixin,
and carprofen, three nonsteroidal anti-inflammatory agents, as postopera-
tive analgesics in two hundred and three horses. Intraoperative butorphanol
(in doses up to 0.1 mg/kg) was administered for analgesia in the periopera-
tive period in horses responding to surgical stimulation. Butorphanol was
used in 47% of the horses undergoing moderate surgical procedures and
79% of those undergoing severe surgical procedures, compared with only
28% of those undergoing mild surgical procedures. The need for further
analgesia was reported significantly reduced in the horses which were given
butorphanol (P ¼ 0.002).

Opioid/sedative drug combinations

A number of investigators have examined the effects of opioids given in
combination with a sedative drug, most commonly an opioid and an
alpha-2 adrenergic agonist such as xylazine or detomidine. The most perti-
nent studies are briefly reviewed below; their results vary in supporting the
use of opioids in horses for notably increased analgesia.
In one of the earliest studies reported, the combination of xylazine and
morphine was subjectively evaluated by Klein and Baetjer [12]. The investi-
gators believed that this combination provided greater sedation/analgesia
than xylazine administration only.
In another study of this drug combination, investigators administered
xylazine (0.66 mg/kg, IV) followed by one of two IV doses of morphine
(either 0.12 or 0.66 mg/kg; experiments one and two were separated by at
least ten days). The authors noted, ‘‘Attempts to compare and quantitate the
degrees of analgesia of horses during experiments 1 and 2 were unrewarding,
50 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60

although it was the opinion of both observers that analgesia was considerably
improved in experiment 2 horses’’ [13].
Stucki et al. [14] compared the analgesic effects of butorphanol (25 lg/kg)
or levomethadone (50 lg/kg) in horses sedated with detomidine (10 lg/kg);
all drugs given IV. They reported a drug-related significant increase in the
threshold of reaction to a noxious stimulus when compared with using deto-
midine alone under similar conditions. In this study, the noxious stimulus
consisted of an electrical current applied to the coronary band and pin pres-
sure applied to the cannon bone.

Evidence of poor or obscure analgesic effect

The analgesic effects of IV xylazine (0.45 mg/kg), pentazocine (0.23 mg/kg),
and meperidine (0.45 mg/kg) have been studied in a balloon-induced model
of equine colic [15]. In this study, xylazine was the only drug that provided
consistent analgesia, whereas pentazocine produced no observable analgesia
and meperidine produced short-term analgesia in only one animal.
Butorphanol (0.1 mg/kg) was compared to detomidine (20 & 40 lg/kg) IV
for sedation and analgesia in horses presented with colic [16]. Butorphanol
was considered ‘‘unsatisfactory’’ as an analgesic 90% of the time in this
population of colic cases.
Brunson et al. used a dental dolorimetry model to test the analgesic
effects of xylazine and xylazine/opioid combinations [17]. All drugs were
given IV and were used at the following dose rates: xylazine (1.1 mg/kg),
morphine (0.75 mg/kg), butorphanol (0.04 mg/kg) and nalbuphine (0.75 mg/
kg). All four analgesic treatments resulted in a marked delay in withdrawal
response. At the measurement times, xylazine alone induced analgesia equal
to that induced with the xylazine/morphine, xylazine/butorphanol, or xylazine/
nalbuphine combinations. These data show no additive or synergistic effect
when opioids were given with xylazine.

Opioid/sedative drug combinations

InvestigatorsÕ conclusions from many studies of opioid-sedative drug
combinations focus on the degree of sedation resulting from the drug combi-
nation. There is little or no information regarding enhanced analgesia asso-
ciated with the addition of the opioid drug. Consider the following examples.
The effects of xylazine/opioid combinations in ponies were compared with
those of acepromazine/buprenorphine by Nolan and Hall [18]. Drug combi-
nations administered IV were as follows: xylazine (0.7 mg/kg) plus methadone
(0.1 mg/kg), xylazine (0.7 mg/kg) plus buprenorphine (4 lg/kg), xylazine
(0.7 mg/kg) plus buprenorphine (6 lg/kg), and acepromazine (0.05 mg/kg)
plus buprenorphine (6 lg/kg). In this study, ‘‘sedation’’ (analgesia was not
evaluated) was greater with the xylazine/opioid combinations than with the
 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60 51

phenothiazine/opioid mixture. There were no obvious differences in the qual-

ity of sedation between the various xylazine/opioid combinations.
The cardiopulmonary and behavioral effects of IV detomidine (10 lg/kg)
alone or in combination with either morphine (0.1 mg/kg), methadone
(0.1 mg/kg), pethidine (1.0 mg/kg), or butorphanol (0.05 mg/kg) were inves-
tigated in horses and ponies by Clarke and Paton. The authors concluded
that the addition of an opioid to the alpha-2 agonist ‘‘. . .increased the
apparent sedation and decreased the response of the animal to external sti-
muli. At doses used, butorphanol produced the most reliable response’’ [19].
The effect of the combination of detomidine plus butorphanol was inves-
tigated in a clinical trial by Taylor and coworkers [20]. They noted, ‘‘The
combination induced a particularly profound sedation and the horses were
apparently unaffected by sounds, tactile stimuli or any surrounding activ-
ity.’’ Their study ‘‘. . .was designed to investigate the effects of the combina-
tion of the two drugs, and no attempt was made to assess the degree of
sedation after detomidine alone and compare it with the effect after the
butorphanol injection.’’
The sedative and cardiovascular effects of romifidine alone (40 and 80 lg/
kg, IV) and in combination with butorphanol (50 lg/kg, IV) were examined
in four ponies and one Thoroughbred by Clarke et al. The investigators
noted, ‘‘the combination with butorphanol reduced the animalsÕ response
to imposed stimuli [i.e., touch, visual and sound stimuli] when compared
with the effect of the same dose of romifidine’’ [21].
In a double-blind, clinical-based study, effects of detomidine (30 lg/kg,
IV), xylazine (1.1 mg/kg, IV), and xylazine plus morphine (1.1 and 0.75 mg/
kg, IV, respectively) were compared. Ninety-nine horses were randomly
assigned to one of the treatments. ‘‘There was no significant difference
between drug treatments related to reactions to the procedure. . .. The study
indicated that all three methods are suitable for standing restraint’’ [22].

The influence of opioids on anesthetic requirement

The concept of the minimum alveolar concentration (MAC) of an inhala-
tion anesthetic that prevents purposeful movement in response to a noxious
stimulus has been used as a tool to examine the analgesic effectiveness of
opioids in horses. MAC represents the ED50 of a given volatile anesthetic
drug. The effects of butorphanol, morphine, and alfentanil have been investi-
gated. To date, MAC studies have not shown any significant effect of opioids
in diminishing anesthetic requirement, and in some instances have been shown
to increase MAC. For example, Steffey et al. studied the effect of both mor-
phine and butorphanol on isoflurane MAC in horses [23]. In this laboratory
study of horses, two results were especially important to clinical application
and differed markedly from results of a comparable study of other commonly
anesthetized species [24]. First, the effect of morphine on anesthetic require-
ment was widely variable. Second, its use was sometimes associated with an
52 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60

undesirable increase in anesthetic requirement! Intravenous doses of 0.2 and

2.0 mg/kg were used. The wide range of change in MAC following low-dose
morphine was )20.2% to +28.3%, whereas the range following high-dose
morphine was even greater, )18.9% to +56.2%. These data clearly do not
support the routine use of morphine as part of a balanced anesthetic technique
in horses anesthetized with isoflurane.
Matthews and Lindsay studied butorphanol on halothane MAC in ponies
[9]. MAC was determined in each pony and they subsequently received butor-
phanol at a dose of either 0.022 mg/kg or 0.044 mg/kg, IV. There was no
important change in MAC following either dose of butorphanol.
The effect of alfentanil on the MAC of halothane has also been examined
by Pascoe et al. [25]. Three constant IV alfentanil infusion rates were used,
and MAC was determined both before opioid administration and then dur-
ing opioid infusion. There were no significant changes in MAC associated
with alfentanil administration. The authors concluded that alfentanil at
plasma concentrations that are known to be effective in humans and dogs
did not induce an appreciable change in halothane MAC.
The effect of acepromazine (0.05 mg/kg) and butorphanol (0.05 mg/kg)
IV on halothane MAC in ponies was investigated by Doherty et al. [26].
Both drugs were given separately and in combination. Acepromazine redu-
ced MAC by an average 36.9%, whereas the combination of acepromazine
and butorphanol led to reduction in MAC of 37.8%. Butorphanol alone
resulted in an average rise of 3% in MAC, which was statistically insignifi-
cant. There was no apparent additive or synergistic effect resulting from the
combination of the phenothiazine and the opioid.
Xylazine has been shown to provide a consistent MAC-sparing effect
when given IV to horses during isoflurane anesthesia [27]. Bennett and Stef-
fey investigated the MAC-sparing effects of xylazine plus morphine [28] and
xylazine plus butorphanol [29] combinations during halothane anesthesia.
Xylazine 0.5 mg/kg was administered IV followed by either morphine (0.1
and 0.2 mg/kg) or butorphanol (0.03 and 0.06 mg/kg) (all doses, IV). MAC
was then re-determined over the following 3 to 4 hours. The combination of
xylazine and morphine did not produce any further reduction in MAC when
compared to xylazine given alone. Anesthetic sparing was 17.9
5.9% for
xylazine plus low dose morphine, and 19.8
3.3% for xylazine plus high
dose morphine, compared to a decrease in halothane MAC of 18.5
6.1%
following xylazine alone. The combination of butorphanol and xylazine
provided no additional MAC reduction compared with xylazine given alone.
Neither morphine nor butorphanol increased the anesthetic sparing effect of
xylazine in horses. These data agree with results of MAC studies per-
formed by other investigators.
Because opioids also cause dose-related central nervous system (CNS)
stimulation in horses, we must be careful in interpreting data that show
either no change or increase in anesthetic requirements (MAC) caused by
opiods in horses. Analgesia induced by opioids should reduce MAC, but
 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60 53

stimulation of the CNS results in an increase in MAC [30,31]. Thus failure

to detect a change in MAC (supra vida) may be caused by central arousal
overwhelming any analgesic action of opioids; or the purposeful movement
in response to the stimulus may be a result of the heightened CNS activity
and arousal in itself, despite any underlying analgesic effect. In any case, cur-
rent data do not strongly support the notion of a beneficial effect of opioid
use, at least during general inhalation anesthesia under clinical conditions
with horses.

Side effects of systemic opioid administration

Behavioral and locomotor effects
Opioids cause a dose-dependent increase in muscle tone and locomotor
activity in horses. Most drugs studied in this regard have been l-opioid ago-
nists and include fentanyl [2,32–34], morphine, methadone, meperidine, pen-
tazocine, anileridine, methadone and hydromorphone [35], alfentanil [36],
and etorphine [37]. Kappa-opioid agonists also induce a locomotor res-
ponse, although the response is generally less marked than that seen with l-
agonists [6,33]. This locomotor response can be abolished by pre-treatment
with naloxone [5].
It is generally considered that the locomotor effect results from dopami-
nergic activity [5,6,38–40]. There is evidence that administration of dopa-
mine antagonists reduces the locomotor response. Results of an attempt
in horses to inhibit the locomotor effects of alfentanil with specific dopamine
antagonists were not encouraging [41].
Nolan et al. [33] found that administration of fentanyl after butorphanol
significantly reduced the effect of butorphanol on locomotor activity. In con-
trast Mama et al. [32] reported that U50488H enhanced fentanyl-induced
locomotor stimulation in horses. The nature of drug interaction in these
studies is still unclear.

Gastrointestinal effects
Opioids and their derivatives are known to increase segmental intestinal
contraction, but the net effect of their action on the gastrointestinal (GI)
tract is constipating, because they cause a prolonged overall depression of
intestinal propulsion [42–47]. Their ability to stimulate forceful muscular
contraction in an already distended bowel suggests a relative contraindica-
tion for use in colicky horses with that condition. Much baseline work
remains to be done regarding GI actions of opioid drugs in horses to better
guide their clinical use as analgesics in equine practice.

Cardiovascular effects
Bradycardia and a mild decrease in or little influence on blood pressure
are usual consequences of opioid use in the anesthetic management of many
species, including dogs. However under similar conditions in horses, opioids
commonly cause an increase in sympathetic stimulation and resulting
54 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60

increases in heart rate, arterial blood pressure, and cardiac output [9,37,
48–51]. Results of a few studies show variance from this usual cardiovascu-
lar response. For example, in the study reported by Robertson and Muir
[52], butorphanol administered in doses of 0.1, 0.2 and 0.4 mg/kg IV did not
cause any significant changes in heart rate, arterial blood pressure, or cardi-
ac output. Systolic arterial blood pressure was significantly increased only
after the 0.2 mg/kg dose of butorphanol. Van Dijk & Nyks [53] investigated
the effects of sufentanil (1 and 2 lg/kg IV) in horses anesthetized with halo-
thane in oxygen. In this study, there was no difference in heart rate with respect
to dose. In addition, arterial blood pressure decreased in all horses after the
administration of sufentanil, but returned to its initial value within a few
minutes. Since sufentanil is a potent l-agonist, it is unclear why the effects
are apparently those of sedation rather than excitation.

Respiratory effects
Respiratory depression (as evidenced by an increase in PaCO2) is generally
considered a regular side effect of opioid use in species other than the horse.
However, the reported influence of opioids on respiration in horses is quite
variable, and results appear strongly related to whether the opioid is adminis-
tered alone or in combination with other drugs. For example, in a study of five
opioids (including morphine) reported by Muir and coworkers, arterial blood
gas values remained unchanged following opioid administration in otherwise
unmedicated horses [50]. Robertson and Muir also reported no change in
PaO2 and PaCO2 in horses given 0.1 or 0.2 mg/kg (IV) butorphanol [52]. In
contrast, studies of opioids administered in association with other drugs, such
as acepromazine [54,55], an alpha-2 agonist [19], or during general anesthesia
[EP Steffey, unpublished observations; 56], indicate they also depress ventila-
tion in horses. Perhaps the CNS arousal effect of the opioid is suppressed by
the concurrently administered drug, thus permitting the commonly expected
respiratory depressant effect to be manifested even in horses. That such mani-
festation is also drug-dose related is supported by personal observations [EP
Steffey, unpublished observations] and the work of Nolan et al. [57].

Abuse potential
Because of the mind-altering effects of opioids, their availability increases
risk for abuse in horses engaged in athletic competition and in humans.
Accordingly, additional considerations associated with regulatory control
are associated with their use.

Opioids administered regionally

Epidural applications
Studies of epidural application of opioids have provided the most convinc-
ing evidence supporting routine clinical use of opioids in horse patients. For
 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60 55

example, postoperative injection of 50 mg morphine into the epidural space

in a 450 kg mare requiring digit amputation produced signs of profound
analgesia within 30 minutes of injection. Because of this, and the need for
prolonged care, an epidural catheter was subsequently placed and further
doses of morphine were administered over the next few days via the catheter.
Alleviation of pain, as evidenced by normal heart rate, prolonged periods of
unremarkable standing behavior, and normal appetite, was seen after each
injection. On the basis of behavioral and physiological parameters, analgesia
in this mare lasted from 8 to16 hours following each epidural injection [58].
Among the best and most convincing laboratory studies of the efficacy of
regional opioid use are those reported by Robinson and Monccada-Suarez
[59] and most recently by Natalini and Robinson [60]. Natalini and Robin-
son studied alfentanil (0.02 mg/kg), butorphanol (0.08 mg/kg), U50488H
(the highly selective kappa-opioid agonist; 0.08 mg/kg), tramadol (a cen-
trally acting, non-opioid analgesic drug; 1.0 mg/kg), and morphine (0.1 mg/
kg). Degree of analgesia was assessed by observing avoidance threshold to
an electrical stimulus applied to the perineal, sacral, lumbar, and thoracic
regions of the body. Butorphanol and U50488H were found ineffective.
Alfentanil mildly but notably increased thresholds, but the results were not
significantly different from control. Only tramadol and morphine produced
consistent, convincing increases in pain thresholds. Onset of action was
slower after morphine than after tramadol.
Epidural morphine (0.1 mg/kg), but not butorphanol (0.05 mg/kg), has
been shown to reduce the end-tidal concentration of halothane necessary
to prevent purposeful response to noxious stimulation (i.e., MAC) of the
pelvic limb of anesthetized ponies [61].
In another recently published laboratory study of mares, meperidine
(0.8 mg/kg) was shown to induce perineal analgesia lasting up to at least
300 minutes. There were minimal sedation, ataxia and cardiopulmonary
effects [62].
Actions of epidural morphine (0.2 mg/kg), have been also studied in
horses in combination with similarly administered detomidine (30 lg/kg)
[63]. In this case, the combination was used to combat pain associated with
experimentally induced hind limb lameness. The drug combination resulted
in a significant decrease in lameness scores for up to six hours after admin-
istration. Unfortunately, there was no comparison made with detomidine or
morphine given alone, so the contribution of morphine to the overall
analgesic effect can not be determined.

Intra-articular administration
There is mounting evidence that opioids can produce potent analgesic
effects by interacting with opioid receptors in peripheral tissues. Studies of
human [64,65] and canine patients [66] indicate that morphine injected
intra-articularly at low dose provides effective analgesia following knee
56 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60

arthroscopy. The analgesia is presumably mediated by local action of mor-

phine on opioid-specific receptors in the synovium [67]. Raekallio et al. [68]
injected morphine (0.05 mg/kg) into the tarsocrural joint of ponies and mea-
sured synovial and plasma morphine concentrations to 24 hours post-
injection. Morphine was detectable in every synovial fluid sample out to and
including 24 hours after the injection. Systemic uptake of morphine
occurred initially; however, neither morphine nor its metabolic products
were detected in plasma at concentrations likely to have any notable sys-
temic effect (serum morphine was below detectable levels by the six-hour
measurement period). RaekallioÕs study and one by Manning and coworkers
[69] found no deleterious reactions from intra-articular morphine injection.
Opioid receptors have been identified in equine synovial membranes
obtained from patients during arthoscopy [3]. Results of these efforts encour-
age further objective study to assess the degree of analgesia resulting from
intra-articular administration of opioids. These data also support at least
selective use of intra-articular injection of morphine to relieve pain after joint
surgery in horses.

Transdermal fentanyl
Fentanyl patches are effectively used in human [70] and small animal
patients [71,72] to provide post-operative pain relief and reduce anesthetic
requirement [73]. Plasma fentanyl levels have been reported following appli-
cation of two 100 lg/hr patches to the lateral surface of the neck in horses
[74]. Fentanyl was rapidly absorbed with plasma levels greater than 2 ng/ml
of plasma 4 hours after application. Peak plasma levels occurred at 6.7
hours, with a peak plasma concentration of 3.85 ng/ml. From 24 to 48
hours, plasma levels fell but remained greater than 1 ng/ml for 54 hours. Plas-
ma drug levels decreased rapidly after patch removal. No adverse behavioral
responses were observed, and there were no changes in heart rate. Unfortu-
nately, there are no published studies regarding the analgesic efficacy of
transdermal fentanyl administration in horses.

Summary and conclusions

Regional administration
There is limited, but convincing, evidence that epidural administration of
morphine and some other l-agonist opioids consistently relieves regional
pain in horses. In addition, this effect is not accompanied by notable unde-
sirable effects. On the other hand, a clinically important analgesic action has
not been demonstrated for similarly administered j-agonist opioids.
There has been little objective data presented to support the analgesic
effectiveness of intra-articularly administered opioids in horses. However,
the evidence of local opioid receptors legitimately encourages work to
 R.C. Bennett, E.P. Steffey / Vet Clin Equine 18 (2002) 47–60 57

substantiate the value of intra-articular opioid administration to relieve

joint-associated pain in horses.

Systemic administration
So far, study results do not provide convincing, objective evidence to sup-
port the opinion that systemically administered opioids consistently and
effectively relieve pain in horses. Given this lack of evidence, and considering
that opioids stimulate locomotor and other forms of unwanted excitant
behavior, reduce propulsive gastrointestinal motility, decrease alveolar ven-
tilation (especially in association with general anesthesia), and require regu-
latory and practical considerations for abuse potential in both humans and
horses, we conclude that routine, indiscriminate administration of opioids
for pain relief in horses is not justified. Identification and focused, objective
study of selective beneficial opioid actions to provide guidance for appropri-
ate clinical use is long overdue.

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