Oski 5.pdf

Clinical Practice Review
Pain management in horses and farm animals
Alexander Valverde, DVM, DVSc, DACVA and Cornelia I. Gunkel, Dr. med. vet., MRCVS
Abstract
Objective: This review discusses the different analgesic drugs and routes of administration used in large
animals for acute pain management. General guidelines and doses are given to assist in choosing techniques
that provide effective analgesia.
Etiology: Noxious stimuli are perceived, recognized, and localized by specialized sensory systems located at
spinal and supraspinal levels.
Diagnosis: Localizing the source of the noxious stimulus as well as understanding the behavioral aspects and
physiological changes that result from such insult is important to adequately diagnose and treat pain. Pain
assessment is far from being definite and objective; not only are there species differences, but also individual
variation. In addition, the behavioral and physiological manifestations vary with the acute or chronic nature of
pain.
Therapy: Pain management should include (1) selecting drugs that better control the type of pain elicited by
the insult; (2) selecting techniques of analgesic drug administration that act on pathways or anatomical
locations where the nociceptive information is being processed or originating from; (3) combining analgesic
drugs that act on different pain pathways; and (4) provide the best possible comfort for the animal.
Prognosis: Providing pain relief improves the animal’s well being and outcome; however, interpreting and
diagnosing pain remains difficult. Continuing research in pain management will contribute to the evaluation
of the pathophysiology of pain, pain assessment, and newer analgesic drugs and techniques.
(J Vet Emerg Crit Care 2005; 15(4): 295–307) doi: 10.1111/j.1476-4431.2005.00168.x
Keywords: a-2 agonists, analgesia, CRI, epidural, intra-articular, ketamine, local anesthetics, NSAID, opioids,
transdermal
Pain Recognition
A noxious stimulus acts on peripheral nociceptive
nerve endings (C- and A-delta fibers) and elicits the
release of neurotransmitters (substance P) by these fib-
ers at the level of the spinal cord or trigeminal system
from where ascending excitatory pathways relay the
information to the brain for the stimulus to be per-
ceived, recognized, and localized as a noxious insult.
The extent of the homeostatic response to pain de-
pends on multiple factors, including the presence of
analgesics before nociception starts (pre-emptive), state
of consciousness of the animal (awake, sedation, an-
esthesia), and control of pain during the inflammatory
phase (post-operative or post-trauma).
Differences in behavior between the different species
of large animals will also impact the way in which the
animal responds to pain, as well as how it should be
approached by the clinician. Horses undergoing surgi-
cal procedures to correct traumatic/functional condi-
tions represent a special group of patients because of
their instinctive flight response to stressful situations.
For example, a rough/violent recovery related to pain
can upset hours of surgical and anesthetic efforts in a
matter of seconds. Providing adequate analgesia to the
animal represents one very important step in making
the animal comfortable and improving outcome.
Pain control should start, if possible, before its onset,
but in most instances, this is only feasible in elective
procedures. Pre-emptive analgesia controls and mini-
mizes the instigation of those pathophysiological mech-
anisms associated with nociception, transmission, and
response. The benefits of pre-emptive analgesia include
the use of a lower dose of analgesic drugs and a more
profound positive response to them. If pain is already
present or is chronic, it might be necessary to use an-
algesic drugs that not only alleviate pain but that also
Address correspondence and reprint requests to:
Alexander Valverde, Department of Large Animal Clinical Sciences, Col-
lege of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
E-mail: valverde@uoguelph.ca
From the Department of Large Animal Clinical Sciences, College of
Veterinary Medicine, University of Florida, Gainesville, FL (Valverde),
Department of Molecular Biomedical Sciences, College of Veterinary
Medicine, North Carolina State University, Raleigh, NC (Gunkel).
Journal of Veterinary Emergency and Critical Care 15(4) 2005, pp 295^307
doi:10.1111/j.1476-4431.2005.00168.x
& Veterinary Emergency and Critical Care Society 2005 295

have an impact on the pathophysiological events that
facilitate the instauration of wind-up and central sen-
sitization during nociception; otherwise, pain control
becomes difficult, and in most instances incomplete,
requiring higher and repetitive doses of analgesics.
Many drugs are available to treat pain, and many
techniques are employed to maximize the effects of
these drugs. Not all drugs are effective for all condi-
tions in which pain is present. In fact, different phar-
macological groups of drugs (polypharmacy) may be
necessary to treat one specific type of painful condition.
In addition, multiple techniques for administering
those drugs may be necessary to control pain in the
best-possible manner. The best pain control may result
from a combination of drugs acting by different mech-
anisms, thus, enhancing analgesia and reducing indi-
vidual drug-related side effects by use of lower doses of
each drug.1
This synergistic or additive analgesia is
common practice; for example, the combination of a
non-steroidal anti-inflammatory drug (NSAID) with an
a-2 agonists or an opioid. However, regardless of the
drug or drug combination chosen, it is crucial to main-
tain regular dosing that prevents pain from being re-
current and chronic.
Regional techniques can be used to augment parental
analgesics. Epidural administration of different drugs,
local anesthetic blocks, and transdermal administration
of opioids are examples of such techniques. However,
pain relief should not replace a thorough diagnostic
evaluation, as pain can be temporarily relieved, but if the
source of the problem is not identified and treated, the
condition of the animal could continue to deteriorate.
Pain assessment in large animals has received less
attention than in small animals. Taylor et al.2
recently
summarized aspects involved in pain recognition in
horses. As is the case for small animals, there is no
single method or parameter that can be used to assess
pain. Objective parameters used to assess pain have
included cardiovascular measurements such as heart
rate and blood pressure, and plasma concentrations of
b-endorphins, catecholamines, and corticosteroids.
Other means of objectively determining the presence
of pain include elaborated methods such as force plate
and gait analysis that are best suited for research con-
ditions and can only assess pain related to specific
conditions that may only affect the extremities. Subjec-
tive parameters include behavioral changes that deviate
from what is considered normal behavior. Because such
changes are interpreted by the observer based on his/
her own experience, interpretation can vary greatly
among clinicians; therefore, its subjective nature may
not necessarily reflect the animal’s true condition. Nev-
ertheless, behavior is what most clinicians use as their
first tool of pain assessment and emphasis continues to
be placed on proper and objective interpretation of the
animal’s behavioral expression.3
In ruminants, apparent stoicism or limited expression
of behavioral indicators of pain can lead to difficult as-
sessment in sheep.4
Although studies in calves and
lambs have shown consistent changes in posture and
locomotor activity after castration or tail docking, be-
havioral changes can have a poor correlation with other
types of noxious stimulus.5
Changes in heart rate and blood pressure, with re-
spect to baseline or accepted normal values, could in-
dicate the presence of pain. However, chronic and acute
pain can result in unexpected changes in both heart rate
and blood pressure. A horse suffering from chronic
pain does not always manifest an increase in heart rate.
In addition, cardiovascular parameters can be influ-
enced by concomitant use of drugs or the autonomic
status of the patient.
Table 1: Doses of parenteral analgesics in the horse
Dose (mg/kg) Route Frequency Notes Reference
Morphine 0.1–0.3 IM, IV q 3–4 h Slow IV injection Mircica et al.14
Meperidine 2–3 IM q 1–2 h
Butorphanol 0.02–0.05
23.7 (mg/kg/min)
IM, IV
CRI
q 2–3 h
Loading dose 0.02 mg/kg
Kalpravidh et al.,7
Sellon et al.8
Xylazine 0.3–1 IM, IV q 2–4 h Jochle et al.,52
Moens et al.,53
Brunson et al.54
Detomidine 0.02–0.04 IM, IV q 2–4 h
Medetomidine 5–7 (mg/kg)
3.5 (mg/kg/h)
IV
CRI
q 2–4 h
Loading dose 5 mg/kg
Bettschart-Wolfensberger et al.,57
Neges et al.58
Romifidine 0.08–0.1 IM, IV q 2–4 h
Ketamine 0.2
40 (mg/kg/min)
IM, IV
CRI
q 2 h Intra-op Muir et al.78
Lidocaine 2–4
50–100 (mg/kg/min)
IV
CRI
q 1–2 h Intra- or post-op.
Loading dose 2–4 mg/kg
Doherty and Frazier44
IM, intramuscular; IV, intravenous; CRI, constant rate infusion.
& Veterinary Emergency and Critical Care Society 2005, doi: 10.1111/j.1476-4431.2005.00168.x
296
A. Valverde and C. Gunkel

b-endorphin, catecholamine, and cortisol concentra-
tions increase when pain is present, but may also in-
crease as a consequence of stress. These substances may
also have a role in intrinsic analgesic control and,
therefore, their concentrations do not necessarily
correlate with the intensity of pain. Measuring these
concentrations under clinical situations is impractical if
pain needs to be recognized in a timely fashion.
In a recent study in the United Kingdom (UK), it was
determined that among veterinarians in specialized
equine practice and general practice, a horse’s behavior
and heart rate were the 2 most commonly used factors
Table 2: Doses of NSAIDs in the horse
Phenylbutazone 2–4 PO, IV q 12 h Reduce to 2 mg/kg
on second day
MacCallister,82
Raekallio et al.85
Flunixin 1 PO, IV, IM q 12 or 24 h Crisman et al.86
Ketoprofen 2–3 IV q 24 h Coakley et al.91
Carprofen 0.7 IV q 24 h Armstrong et al.94
Eltenac 0.5 IV q 24 h Goodrich et al.95
Vedaprofen 1 IV q 24 h Lees et al.96
Meloxicam 0.6 IV q 12 h Sinclair et al.97
IM, intramuscular; IV, intravenous; PO, per oral; NSAID, non-steroidal anti-inflammatory drug.
Table 3: Doses of epidural, transdermal, and intra-articular analgesics in the horse
Morphine 0.1 EPIn
q 12–24 h Diluted to 15–30 mL with saline Valverde et al.,24
Natalini and Robinson,25
Sysel et al.,28
Goodrich et al.29
0.2 EPI q 12–24 h Combined with detomidine (30 mg/kg)
0.1 IAw Once Diluted to 5–20 mL with saline
Tramadol 1 EPI q 6 h Natalini and Robinson25
Fentanyl 10 mg/150–200 kgz TDP§ q 48–72 h mg/150–200 kgz Maxwell et al.,35
Wegner et al.36
Xylazine 0.2 EPI q 3–4 h Diluted to 5–10 mL with sterile saline LeBlanc and Caron,68
Skarda and Muir,69
Doherty et al.70
Detomidine 0.03–0.06 EPI q 3 h Diluted to 5–10 mL with saline Skarda and Muir30
Ketamine 0.8–2 EPI q 1–2 h Diluted to 5–10 mL with saline Doherty et al.,13
Gómez de Segura et al.80
Lidocaine 0.2–0.25 EPI q 1 h Schelling and Klein47
Ropivacaine 0.8 EPI q 3–4 h Skarda and Muir48
n
Epidural.
wIntra-articular.
§
Transdermal patch.
Table 4: Doses of parenteral analgesics in ruminants
Morphine 0.05–0.4 IM, IV q 6–8 h Slow IV injection George,15
Pinheiro Machado et al.16
Meperidine 5 IM, IV q 1 h Sheep Nolan et al.22
Butorphanol 0.05–0.2 IM, IV q 2–3 h Sheep, goat, llama Doherty et al.,17
Waterman et al.,18
Carroll et al.23
Buprenorphine 0.0015–0.006 IM, IV q 1–3.5 h Sheep Waterman et al.19
Fentanyl 0.01 IV q 2 h Sheep Waterman et al.21
Xylazine 0.05–0.2 IM, IV q 2–4 h George,15
Celly et al.,61
DeMoor and Desmet,62
Kumar and Thurmon63
Detomidine 0.003–0.01 IM, IV q 2–4 h Celly et al.61
Medetomidine 0.005–0.01 IM, IV q 2–4 h Celly et al.61
Romifidine 0.003–0.005 IM, IV q 2–4 h Celly et al.61
IM, intramuscular; IV, intravenous.
& Veterinary Emergency and Critical Care Society 2005, doi: 10.1111/j.1476-4431.2005.00168.x 297
Horses and farm animals

determining whether an analgesic was given and what
dose was used.6
In addition, according to this survey,
personal experience of the veterinarian outranked pre-
vious undergraduate education and continuing profes-
sional development on pain topics, as the tool used by
the veterinarian, to detect and interpret pain.6
More
research needs to be done to implement and standard-
ize adequate means of pain evaluation in order to ef-
fectively recognize and treat pain. In the meantime, it is
best to administer analgesics when in doubt.
Analgesic Drugs
The use of opioids, local anesthetics, a-2 adrenergic
agonists, ketamine, and non steroidal anti-inflamma-
tory drugs (NSAIDs) is discussed in the following
sections.
Opioids
This group of drugs has been traditionally adminis-
tered by the intramuscular (IM) or intravenous (IV)
route in the horse. In recent years, other routes includ-
ing epidural and transdermal administration have
gained popularity because of their effectiveness in pain
management.
In the non-painful animal, opioids can induce excite-
ment or behavior changes if administered alone or to
mildly sedated animals. However, it is generally ac-
cepted that if pain is present, these side effects are less
commonly observed.
Opioids are potent analgesics and although their use
is made cumbersome by regulation, this should not
prevent usage of these drugs as their benefits outweigh
this inconvenience. Agonist of the m receptor (mor-
phine, fentanyl, meperidine) are considered better in
controlling orthopedic pain than k-agonists (but-
orphanol) (Table 1). Butorphanol, a k-agonist and m-
antagonist has been recommended for superficial and
visceral pain relief lasting 30–90 minutes in horses.7
Constant rate infusion (CRI) of butorphanol (loading
dose of 17.8 mg/kg, followed by an infusion of 23.7 mg/
kg/hr) causes less adverse behavioral and gastrointes-
tinal effects than a single injection (0.1–0.13 mg/kg)
and maintains the analgesia for as long as the CRI is
administered.8
The effects of injectable drugs on the minimum al-
veolar concentration (MAC) of any particular inhalant
anesthetic may be used as an indicator of analgesic po-
tency of that particular injectable drug. MAC is the end-
tidal concentration required to prevent purposeful
movement in response to a noxious stimulus in 50%
of the population. IV administration of morphine (0.25
or 2 mg/kg) to anesthetized horses did not induce a
consistent sparing effect on the MAC of isoflurane, de-
spite the analgesic properties of morphine. The low
dose changed MAC by 20% to 128%, whereas the
high dose changed it between 19% and 56%.9
Similarly,
Table 5: Doses of NSAIDs in ruminants
Phenylbutazone 2–6 PO, IV q 24 h Prohibited in dairy cattle over
20 months of age
Skarda and Muir,48
DeBacker et al.99
Flunixin 1 PO, IV, IM q 12 or 24 h
Ketoprofen 3 IV, PO q 24 h Faulkner and Weary,101
Stafford et al.102
Carprofen 0.7 IV q 24–48 h Sheep Welsh et al.103
Aspirin 100 PO q 12 h Gingerich et al.98
IM, intramuscular; IV, intravenous; NSAID, non-steroidal anti-inflammatory drug; PO, per oral.
Table 6: Doses of epidural analgesics in ruminants
Dose (mg/kg) Frequency Notes Reference
Morphine 0.1 q 6–12 h Diluted with 0.05–0.2 mL/kg of saline George,15
Pablo,26
Hendrickson et al.27
0.1 q 6–12 h Combined with bupivacaine (1.5 mg/kg)
Medetomidine 0.015 q 7 h Diluted to 5 mL with saline St. Jean et al.72
Xylazine 0.05 q 2 h Diluted to 5 mL with saline.
Report of demyelination in cattle
St. Jean et al.,72
Chevalier et al.73
George,15
Detomidine 0.04 q 3 h Diluted to 5 mL with saline Prado et al.71
Ketamine 0.5–2 q 1 h Diluted to 5–20 mL with saline Lee et al.81
Lidocaine 0.2–0.4 q 1–3 h Skarda49
Veterinary Emergency and Critical Care Society 2005, doi: 10.1111/j.1476-4431.2005.00168.x
298

butorphanol did not produce significant changes on the
MAC of halothane in horses at IV doses of 0.022 and
0.044,10
or 0.05 mg/kg.11
A likely explanation is that the
excitatory effects of morphine and butorphanol on the
central nervous system in horses may predominate
over their analgesic effect.12
Moreover, morphine ad-
ministered epidurally using a lower dose than the dos-
es used IV (0.1 versus 0.25 or 2 mg/kg, respectively)
decreased the MAC of halothane in ponies.13
Possibly,
the systemic effects of this epidural dose has minimal
effects on the brain. Despite the lack of a consistent
sparing effect of parenteral morphine or butorphanol
on inhalant requirements, this should not preclude
their use in the anesthetized horse, as the analgesic ef-
fects are present but masked by the excitatory effects
and the analgesia may prove beneficial to the patient in
the immediate postoperative period. Pain that arises
from trauma, inflammation, and surgery may have
more serious consequences than pain inflicted as a
supramaximal stimulus in MAC studies, as the latter
stimulus is only temporarily applied during MAC de-
termination and has no persistent effects, whereas the
former causes of pain may elicit a series of pathophys-
iological events that if not controlled may lead to fur-
ther pain. In a recent retrospective study in horses
anesthetized for a variety of soft-tissue and orthopedic
procedures with romifidine, ketamine, diazepam, and
halothane, no increased risk for side effects in the intra-
or post-operative period was noted in horses receiving
morphine (0.1–0.17 mg/kg IV) intra-operatively when
compared with horses that did not receive it14
(Table 1).
In ruminants (Table 4), morphine (0.05–0.1 mg/kg IV
or IM) has been recommended, and doses as high as
10 mg/kg have been used in goats.15
It has also been
stated that morphine has poor analgesic properties in
ruminants.15
In contrast, using a thermal threshold as-
say in cattle, morphine induced dose-dependent anal-
gesia without adverse behavioral or locomotor effects
when cumulative doses of up to 0.4 mg/kg were ad-
ministered IV.16
In goats, butorphanol (0.05 or 0.1 mg/kg IV) affected
the MAC of isoflurane inconsistently as it increased,
decreased, or did not change MAC in the population
studied.17
In sheep, both butorphanol (0.05, 0.1, or
0.2 mg/kg IV) and buprenorphine (1.5 or 6 mg/kg IV)
were effective against a thermal but not against a me-
chanical model of nociception.18–20
Duration of analge-
sia for both butorphanol and buprenorphine was dose
dependent, lasting 60–180 minutes for each dose of
butorphanol, and 40–210 minutes with each dose of
buprenorphine.18–20
Conversely, the pure m agonists,
fentanyl (10 mg/kg IV) and meperidine (5 mg/kg IV),
were effective against both thermal and mechanical
stimuli in the same nociceptive model.21,22
Duration of
analgesia against the thermal stimulus was 30 minutes
for meperidine and 110 minutes for fentanyl, whereas
duration against the mechanical stimulus was 15 min-
utes or less for meperidine and 60 minutes for fent-
anyl.21,22
In another study in sheep using an electrical
stimulus, analgesic effects could not be detected for
buprenorphine (5 mg/kg IM) or methadone (0.6 mg/kg
IM), whereas xylazine (0.05, 0.1, and 0.2 mg/kg IM) was
effective.4
In llamas, butorphanol (0.1 mg/kg IM) produced so-
matic analgesia of different degrees in different body re-
gions (withers, midneck, and metacarpus) for 2 hours or
less; however, 2/6 llamas showed signs of excitement.23
Epidural
The use of opioids by the epidural route (first coccygeal
or sacrococcygeal interspace) has been described in the
horse, cattle, and goat13,15,24–27
(Tables 3 and 6). The
presence of opioid receptors in the spinal cord facilitate
the action of opioids injected epidurally. The main ad-
vantage of epidural administration relates to the prox-
imity of the injected drug to the site of action (spinal
cord), which usually allows use of a lower dose and
produces more prolonged analgesia, particularly when
opioids with low lipid solubility, such as morphine, are
used.24,25
Tramadol (1 mg/kg), a non-opiate analgesic, when
administered epidurally in horses to produce analgesia
against a noxious electrical stimulus in the perineal and
sacral areas, had a more rapid analgesic onset (30 min-
utes or less) than 0.1 mg/kg morphine (5–6 hours). Both
drugs provided 4–5 hours of complete analgesia.25
However, the slow onset of morphine in this research
model is in contrast to clinical impressions of morphine
having a shorter onset (30–60 minutes) and longer du-
ration of analgesia (8–16 hours) in a horse suffering
from traumatic pain.24
Differences in the type of nox-
ious stimulus between the research and clinical setting
could be responsible for such variation.
In other studies, a larger epidural dose of morphine
(0.2 mg/kg) combined with detomidine (30 mg/kg) re-
sulted in analgesia that was present 6 hours post-injec-
tion in induced traumatic synovitis,28
and at 14–16
hours post-injection in horses undergoing bilateral ar-
throscopy.29
Detomidine’s duration of action when in-
jected alone epidurally is 2.5 hours.30
The combination
of opioid and a-2 agonists results in a synergistic action
that may result from pharmacokinetic interactions or
receptor-mediated enhancement of G-protein-coupled
mechanisms by both groups of drugs.31,32
Clinically, the
benefit of the combination is a faster onset and more
prolonged analgesia.
Epidural morphine has a sparing effect in both tho-
racic and pelvic limbs in small animals and, therefore, it
Veterinary Emergency and Critical Care Society 2005, doi: 10.1111/j.1476-4431.2005.00168.x 299

is used in these species as an analgesic technique for
pain that arises below the neck area.33
In large animals,
epidural morphine at 0.1 mg/kg and diluted to
0.15 mL/kg of saline administered to anesthetized po-
nies, reduced the MAC of halothane by 14% in the pel-
vic limb but had no effect in the thoracic limb.13
It is
possible that in large animals, the size of the epidural
canal and the distance from the site of injection to ros-
tral areas affects the absorption and cephalad distribu-
tion of morphine into the cerebrospinal fluid. Therefore,
clinical use of epidural morphine in large animals
should be reserved for pain arising in the pelvic limb
and perhaps the abdominal area.
For those cases where pain is likely to be present for
days to weeks, placement of epidural catheters allows
repeated injections without having to place a needle
into the epidural space each time that pain manage-
ment is necessary. The advantage of the epidural tech-
nique is that a single dose of morphine may provide
analgesia for up to 12 hours or longer and requires only
1/3–1/5 of the dose used IM or IV, and which may last
only 3–4 hours. Combinations of morphine and the a-2
agonists (xylazine, detomidine) are commonly used
epidurally for long-term pain management. The ad-
verse effects of long-term catheters are minimal if asep-
tic technique is observed during placement of the
epidural catheter and subsequent analgesic injections.
Localized inflammation and fibrosis at the lumbosacral
and sacral segments with no related systemic effects
have been described in horses catheterized for 14 days
and receiving injections twice a day during that period;
thus epidural catheter placement may be considered a
safe technique.34
Butorphanol has proven less effective by the epidural
route. Using an avoidance model with electrical stim-
ulation to the perineal, sacral, lumbar, and thoracic re-
gions, butorphanol at 0.08 mg/kg did not produce an
analgesic effect in horses.25
In anesthetized ponies,
butorphanol at 0.05 mg/kg did not affect the MAC of
halothane.13
The dose of epidural morphine (first coccygeal inter-
space) that has been used in ruminants is also 0.1 mg/
kg and although its duration of analgesia has not been
assessed thoroughly, it appears that it may last for at
least 6 hours; similar to findings in other species.15,26,27
Transdermal
Another novel technique is the use of transdermal fent-
anyl patches for treating painful conditions (Table 3). In
the horse, the patches are best placed on the shaved
antebrachium of forelimbs and covered with bandage
material. Fentanyl, at a total dose of 20 mg using 10 mg
patches, results in rapid absorption after place-
ment (o1 hour), achieving concentrations consistent
with analgesia that are maintained over a period of
2–3 days.35,36
The bioavailability is almost complete
(96%).35
Continuous transdermal administration for 8–9
days with the patches replaced at intervals of 48–72
hours were well-tolerated and maintained plasma con-
centrations similar to the single dose.35
In pigs, peak concentrations may take up to 24 hours
to be achieved.15
In goats, peak plasma concentration of
fentanyl was quite variable and was reached 8–18 hours
after the transdermal patch (50 mg/hr) was placed on
the neck.37
Bioavailability was 4100% because of recy-
cling of fentanyl through a ruminosalivary cycle, that is
common for lipid-soluble drugs like fentanyl. A conse-
quence of the rumenosalivary cycle is that the use of
transdermal patches in ruminants requires close super-
vision in order to detect side effects associated with
higher than expected plasma concentrations.37
Intra-articular
Opioid m-receptors have been identified in synovial
membranes of horses using immunohistochemical anal-
ysis and radioligand binding of tissue homogenates.38
Opioids may be especially useful when administered
by the intra-articular route because inflammation up-
regulates opioid receptors in the joint. Intra-articular
morphine produces effective and prolonged analgesia.
In dogs undergoing stifle arthrotomy, intra-articular
morphine (0.1 mg/kg diluted with 1 mL/10 kg of sa-
line) provided long lasting analgesia (at least 6 hours)
that was comparable with the analgesia induced by the
same dose of epidural morphine.39
In human an-
esthesia, it is common to administer the combination
of the local anesthetic bupivacaine and morphine be-
cause of the synergistic action of both drugs that results
in better analgesia.40
In dogs, bupivacaine had a greater
analgesic effect than morphine.41
Although the drugs
were not combined in the latter study, it is common
practice to do so in small animals, based on the human
studies. Conversely, in large animals, it is preferred to
use morphine alone (Table 3) because of the perception
of surgeons that the local anesthetic may interfere with
cartilage healing, although there is no evidence that
supports this.
Local Anesthetics
Local anesthetic blocks are very effective in providing
analgesia that prevents behavioral reactions associated
with pain. In general, local anesthetic blocks are easy
to perform and can represent an important adjunct
to other modes of pain relief. In calves undergoing
dehorning with or without sedation with xylazine
and butorphanol, it was demonstrated that only those
300

calves receiving a cornual nerve block did not show
vigorous head jerks during dehorning.42
The mechanism of action of local anesthetics involves
blockade of sodium channels which prevents nerve de-
polarization. Use of local anesthetics (bupivacaine,
lidocaine, mepivacaine) by perineural infiltration, in-
tra-articular or epidural injection provides excellent an-
algesia. Numerous reviews are available on perineural
blocks for the different species and will not be dis-
cussed here.43
In addition, lidocaine has been used IV as a CRI to
provide analgesia in the anesthetized horse (Table 1).
The analgesic effect reduces inhalant requirements and
provides post-operative analgesia. A loading IV dose of
2.5–5 mg/kg followed by infusion of 50–100 mg/kg/min
decreased halothane requirements in ponies in a dose-
dependent manner. Serum lidocaine concentrations
between 5 and 7 mg/mL decreased MAC by 40–70%,
whereas concentrations of less than 2 mg/mL had
minimal effects.44
Interestingly, concentrations of 1.8–
4.5 mg/mL correlate with toxic clinical signs, such as
alterations in visual function, anxiety, ataxia, and col-
lapse, in awake horses administered a loading dose of
1.5 mg/kg and an infusion of 300 mg/kg/min.45
Lidocaine by CRI has been used similarly in small
animals46
and may have applications in other large an-
imal species, although no controlled studies have been
reported yet.
Epidural
Epidural local anesthetics can induce sensory, motor,
and sympathetic blockade. The effects are dose related.
A low dose of local anesthetic injected epidurally at the
first coccygeal or sacrococcygeal interspace can provide
adequate analgesia of the perineal area through block-
ade of sensory fibers without affecting motor or sym-
pathetic function. Higher doses can travel rostrally and
block all types of fibers, causing ataxia/paresis and
hypotension. Ruminants can tolerate recumbency be-
cause of ataxia; however, this side effect is unacceptable
in horses. Epidural injections at the lumbosacral inter-
space in the horse or ruminants can result in blockade
of spinal lumbar and sacral segments that exacerbate
ataxia and recumbency. In addition, risk of sub-
arachnoid injection is likely, because of the more diffi-
cult nature of this technique. Therefore, recommended
doses for the horse and cattle in this review refer to
sacrococcygeal or coccygeal interspace epidural injec-
tion (Tables 3 and 6).
The recommended dose of lidocaine in horses is 0.2–
0.25 mg/kg (1–1.25 mL of 2% lidocaine/100 kg) and
causes analgesia in 6–10 minutes for a period of 45–60
minutes.47
Ropivacaine is longer acting than lidocaine
and causes analgesia within 10 minutes for a period of
196 minutes using a dose of 0.8 mg/kg (1.6 mL of 0.5%
ropivacaine/100 kg) with minimal ataxia and cardio-
respiratory effects.48
Epidural bupivacaine (1.5 mg/kg) or epidural mor-
phine (0.1 mg/kg) in goats administered at the lumbo-
sacral interspace after surgery provided better pain
relief than saline after abdominal surgery.27
Lidocaine is
often used in cattle, goats, and sheep at a dose of 0.2–
0.4 mg/kg; onset of analgesia takes 5–20 minutes and
has a duration of 30–150 minutes.49
In pigs kept at a superficial plane of isoflurane an-
esthesia, epidural lidocaine (5 mg/kg) injected at the
lumbosacral interspace produced analgesia within 2
minutes and lasted for 60 minutes. This dose resulted in
a decrease in heart rate, blood pressure, respiratory
rate, tidal volume and PaO2, and an increase in PaCO2
in the first 30–45 minutes post-administration.50
Intra-articular
In sheep undergoing stifle arthrotomy, intra-articular
lidocaine (40 mg) prior to incision, and bupivacaine
(10 mg) after closure, were effective in lowering pain
scores compared with a control group. Analgesia was
effective for 3–7 hours post-operatively.51
a-2 Adrenergic Agonists
This group of drugs (xylazine, medetomidine, detomi-
dine, romifidine) activate descending antinociceptive
fibers and interfere with release of nociceptive neuro-
transmitters (substance P). a-2 adrenergic receptors are
located in the central nervous system and periphery,
therefore, parenteral and epidural administration have
been used. Their location at the level of the superficial
laminae of the dorsal horn makes epidural administra-
tion feasible and effective.
a-2 agonists have been extensively used to alleviate
visceral pain in the horse (Table 1). Their potent sed-
ative effects also contribute to the analgesic manage-
ment of orthopedic pain. Xylazine, detomidine, and
romifidine have all been used as analgesics for abdom-
inal and somatic pain.52,53
Reference doses are xylazine
(1.1 mg/kg), detomidine (20 mg/kg), and romifidine
(80 mg/kg). Xylazine (1.1 mg/kg IV) was as effective
as xylazine/butorphanol (1.1 mg/kg/ 0.04 mg/kg IV),
xylazine/morphine (1.1 mg/kg/0.75 mg/kg IV), or
xylazine/nalbuphine (1.1 mg/kg/0.75 mg/kg IV) in in-
creasing tooth pulp pain thresholds elicited by electrical
stimulation.54
Nevertheless, it is common practice to
combine a-2 agonists with opioids because of the per-
ception that the combination produces better sedation
and analgesia than when each agent is administered
alone.55,56

Use of medetomidine as a CRI has been described for
standing sedation in horses, using a loading IV dose of
5 mg/kg and a CRI of 3.5 mg/kg/hr.57
In contrast to op-
ioids that have not shown a consistent and predictable
effect on decreasing the inhalant anesthetic require-
ments (MAC), the sedative and analgesic effects of
a-2 agonists cause a dependable reduction. In a recent
clinical trial in horses undergoing different types of
orthopedic and soft-tissue surgical procedures and ad-
ministered medetomidine (7 mg/kg IV) as part of the
pre-medication, followed by a CRI at 3.5 mg/kg/hr
during anesthesia with isoflurane, 20% less isoflurane
was required (end tidal of 1.07 0.19% versus
1.33 0.13%) than in horses that received xylazine
(1.1 mg/kg IV) as the premedication and no CRI.58
An-
esthetic concentrations were based on clinical assess-
ment for maintaining an adequate surgical plane. In the
research setting, xylazine (0.5 mg/kg IV) decreases
MAC of halothane by approximately 20%,59
and dos-
es of 0.5 and 1 mg/kg IV) decreased the MAC of iso-
flurane by 24–35% in a dose- and time-dependent
fashion.60
The addition of an opioid to an a-2 agonist
has not resulted in a further decrement in the MAC
obtained with the a-2 agonist alone.59
However, in
treating pain, it is generally accepted that polypharma-
cy is advised to improve outcome.1
In ruminants, as for other species, a-2 agonists pro-
vide intense analgesia (Table 4); however, strong
sedative and cardiorespiratory effects are present at
analgesic doses. Decreased oxygen partial pressure in
arterial blood is common with xylazine, detomidine,
medetomidine, and romifidine. The degree to which
PaO2 is decreased differs between sheep, cattle, and
goats, although the small ruminants are more affect-
ed.61–63
Doses of 0.05–0.2 mg/kg for xylazine, 5–10 mg/
kg for medetomidine, 3–10 mg/kg for detomidine, and
5 mg/kg for romifidine, IM or IV have been recom-
mended in ruminants. In cattle and sheep, xylazine has
been demonstrated to increase myometral tone and
caution is advised in the pregnant animal.64,65
Similar
effects are likely in other species, although reports are
not available. The effects of other a-2 agonists
on myometral tone have also not been thoroughly
investigated.
In llamas, medetomidine (0.03 mg/kg IM) provided
analgesia to needle prick in the flank and perineal area
within 13 minutes and lasted for 60 minutes; however,
excessive sedation and recumbency was observed.66
Epidural
The main side effects of epidural a-2 agonists are ataxia,
sedation, and cardiovascular effects (such as bra-
dycardia, atrioventricular conduction block, hyperten-
sion, and/or hypotension), as a result of systemic ab-
sorption and local effects. Xylazine usually requires
a lower epidural dose than that used systemically,
therefore, side effects can be minimized. Detomidine
requires a dose similar to the parenteral dose, hence,
ataxia can be more profound than is usually seen with
xylazine given epidurally.30,67
Epidural administration provides analgesia of longer
duration than is seen with the IM or IV route (Table 3).
In horses, doses of 0.17–0.22 mg/kg of xylazine can re-
sult in surgical analgesia of the perineal area that starts
within 15–30 minutes and lasts for up to 3.5 hours.68,69
Likewise, detomidine at 0.06 mg/kg produces analgesia
that has an onset of 10–25 minutes and lasts for
42 hours.30
The effect of inter-coccygeal epidural xylazine on in-
halant requirements is greater and segmental (affects
both pelvic and thoracic limbs) than for morphine and
ketamine in ponies.13,70
MAC reductions are less and
only detectable at the pelvic limb with ketamine and
morphine, whereas xylazine at 0.15 mg/kg and diluted
with saline to a final volume of 0.15 mL/kg reduced the
MAC of halothane in a segmental manner both in the
pelvic and thoracic limb, by 43% and 34%, respective-
ly.13,70
This makes epidural administration of xylazine
potentially useful for painful conditions arising from
anywhere between the pelvic and thoracic limb, al-
though its use has been limited to pain that involves the
perineal area and pelvic limb. Further studies are nec-
essary to determine if epidural xylazine has clinical
applications for pain arising from rostral areas.
After epidural or IM administration in cattle,
0.04 mg/kg of detomidine produced similar analgesia
of the perineum and flank for up to 3 hours.71
Sedation,
ataxia, cardiorespiratory effects (bradycardia, hyper-
tension/hypotension, bradypnea, hypoxemia, and
hypercarbia), and decreased ruminal motility are com-
mon after epidural administration of a-2 agonists in
ruminants; as the rate of absorption of a-2 agonists from
the epidural space is similar to that after IM injection,
similar systemic side effects are to be expected. Epi-
dural xylazine (0.05 mg/kg) has a slower onset of action
than detomidine (10–20 minutes versus 5 minutes)71,72
and its analgesic effects last for 2 hours72
(Table 6).
Epidural xylazine (0.05 mg/kg) administered before a
paravertebral nerve block in heifers caused less distress
and pain during the administration of the local block
when compared with a placebo group.73
One author
has warned against the use of xylazine epidurally, be-
cause of demyelination of lumbar spinal cord segments
and irreversible paralysis in 3 cows that received this
drug.15
Epidural medetomidine (15 mg/kg diluted with sa-
line to a final volume of 5 mL) in cattle resulted in
perineal analgesia within 5–10 minutes that lasted for
302

almost 7 hours; however, ataxia and sedation were also
observed.74
In pigs, epidural injection at the lumbosacral space of
0.2 mg/kg of xylazine provided at least 90 minutes of
analgesia with an onset of action 15–20 minutes after
administration with no cardiorespiratory effects except
for a decrease in heart rate 60–90 minutes post- admin-
istration.50
A higher dose of xylazine (2 mg/kg) in-
duced immobilization and analgesia from the anus to
the umbilical area within 5 minutes of injection and
lasted for at least 120 minutes, whereas detomidine
(0.5 mg/kg) induced immobilization within 10 minutes
and analgesia lasted only 30 minutes.75
Ketamine
Ketamine has been used commonly as part of the an-
esthetic regimen for most species. More recently, it has
gained popularity used at subanesthetic doses to pro-
duce analgesia. The analgesia is because of antagonism
of N-methyl-D-aspartate (NMDA) receptors, inhibiting
the excitatory actions of glutamate; this reduces sen-
sitization and wind-up during pain.76,77
Ketamine is
effective in treating neuropathic and nociceptive pain at
subanesthetic doses and does not cause any of the side
effects that have been associated with doses that pro-
duce dissociative anesthesia, such as tremors, tonic
spasticity, or convulsive seizures.
In the anesthetized horse, ketamine (Table 1) admin-
istered as an infusion (up to 40 mg/kg/min) decreased
the MAC of halothane in a dose-dependent fashion to a
maximum of 37% and this change was accompanied by
an increased cardiac output.78
Ketamine infusions at
lower infusion doses (10 mg/kg/min intra-operative
and 2 mg/kg/min post-operative) have been used in
the dog as an analgesic.79
No studies have been report-
ed in other species; however, because of ketamine’s in-
tense analgesic effects, it is likely that it will prove
beneficial in other large species.
Epidural
Epidural administration of ketamine blocks the NMDA
receptors in the spinal cord. In horses, analgesia of the
tail, perineum, and upper hindlimb was present within
10 minutes in a dose-dependent manner (30 minutes for
0.5 and 1 mg/kg, and 75 minutes for 2 mg/kg; diluted
with saline to a final volume of 0.02 mL/kg) (Table 3).
Systemic absorption of the ketamine also caused seda-
tion for 15–30 minutes and ataxia in 1/6 horses at the
highest dose.80
In anesthetized ponies, epidural keta-
mine (0.8 or 1.2 mg/kg, diluted with saline to a final
volume of 0.15 mg/kg) decreased the MAC of halo-
thane by 13–17% in the pelvic limb.13
In cattle, epidural ketamine (0.5, 1.0, and 2.0 mg/kg,
diluted to a volume of 5, 10, and 20 mL, respectively)
induced dose-dependent perineal analgesia without se-
dation (17, 34, and 63 minutes, respectively) (Table 6).
Analgesia assessed by superficial and deep muscular
pinpricks was present in approximately 5 minutes and
ataxia occurred with the intermediate and high dose.81
NSAIDs
Inflammation is a major component of injury and pain.
Therefore, NSAIDs are commonly used as part of a
balanced analgesic technique, because of their inhibi-
tory actions on the cyclo-oxygenase enzymes (COXs)
necessary for prostaglandin production during the in-
flammatory response. Two types of COX enzymes are
commonly recognized, COX-1 – involved in homeo-
static functions of the gastric mucosa, kidney perfusion,
and platelet function, and COX-2 – present in inflam-
matory events, although it also has an important role in
kidney perfusion and gastrointestinal healing. Ideally,
based on in vitro studies, NSAIDs should be more spe-
cific for COX-2 than COX-1 in order to spare most of
homeostatic functions. However, in vivo both groups of
NSAIDs may affect homeostatic functions and result in
adverse side effects.
Unlike other analgesic drugs, plasma concentrations
of NSAIDs are not always correlated with analgesic ef-
fects. Even when no drug can be detected in plasma,
their concentrations at the tissue level may be sufficient
to cause an anti-inflammatory effect that contributes to
analgesia (Table 2).
Newer NSAIDs are reported in the literature, how-
ever, most of the studies emphasized pharmacokinetic
data rather than analgesic properties or uses of the
drugs. Nevertheless, NSAIDs should be considered as
adequate drugs for mild-to-moderate pain when used in
combination with the other groups of analgesic drugs.
In horses, phenylbutazone, flunixin meglumine, and
ketoprofen continue to be the most commonly used
NSAIDs (Table 2). All of these drugs inhibit the COX-1
enzyme; therefore, there is high risk of gastric ulcera-
tion and renal impairment. Phenylbutazone (2–4 mg/
kg) appears to be the most toxic member of this
group,82
and is approved by the Food and Drug Ad-
ministration (FDA) in horses and dogs. Signs of toxicity
for most NSAIDs may progress from inappetence
and depression to colic, gastrointestinal ulceration,
and weight loss.83,84
In horses recovering from art-
hroscopic surgery, phenylbutazone (4 mg/kg IV before
pre-medication; followed by 2 mg/kg IV q 12 h for 60 h)
improved analgesic outcome when compared with a
placebo group, although cortisol and b-endorphin con-
centrations were similar in both groups.85

Flunixin is commonly used for treating colic pain
(1 mg/kg IV). In foals less than 24-hours old, phar-
macokinetic data suggest increasing the dose by as
much as 1.5 times the adult dose to achieve comparable
therapeutic concentrations; however, longer dose inter-
vals are necessary to avoid toxicity in foals.86
Phenylbutazone and flunixin are available as oral and
injectable forms. The oral form simplifies treatment
when long-term therapy (days to weeks) is necessary.
Ketoprofen is available only as an injectable formulation.
Clearance of phenylbutazone in miniature and stand-
ard donkeys is more rapid than in horses (6 versus 2.8
versus 0.5 mL/kg/min; miniature donkey, standard
donkey, horse). Similar findings have been reported
for flunixin meglumine in donkeys, mules, and horses.
In general, donkeys have more rapid clearance, mules
are intermediate, and horses have slower clearance
(1.78 versus 1.4 versus 1.14 mL/kg/min; donkey, mule,
horse).87
Therefore, more frequent administration
has been suggested in those species with faster clear-
ances, although the dosage regime has not been yet
determined.87–89
Conversely, carprofen is more slowly
metabolized in donkeys than horses, therefore, less fre-
quent administration may be necessary.90
Ketoprofen (2.2 mg/kg IV SID) has been recommend-
ed in horses.91
In foals less than 24-hour old, the vol-
ume of distribution is larger and the clearance is
reduced, indicating that this drug has a longer elimi-
nation half-life in foals.92
In ponies, synovial concen-
trations of ketoprofen are achieved after IV injection
and will last for up to 4 hours.93
Carprofen (0.7 mg/kg IV) is licensed for use in horses
in the UK. This NSAID has no significant cyclo-oxy-
genase activity in vivo, and has a longer elimination
half-life and clearance than ketoprofen. Like other
NSAIDS, penetration into synovial fluid is significant.
In normal synovial fluid, carprofen concentrations peak
at 12 hours and are still detectable at 48 hours.94
The
onset time may be even quicker in inflamed joints.
Other NSAIDs that have been reported in the horse
include eltenac (0.5 mg/kg IV) that induced minimal
side effects.95
Vedaprofen is structurally related to keto-
profen and carprofen. It is approved for use in the horse
at a dose of 1 mg/kg IV, and has very similar phar-
macokinetic and pharmacodynamic properties to keto-
profen.96
Meloxicam (0.6 mg/kg IV) has a short half-life
and large clearance in horses, suggesting that it needs
to be dosed more than once a day; this is at variance
with the dog where it may be given only once daily.97
In ruminants, phenylbutazone, flunixin, ketoprofen,
and aspirin are the most commonly used NSAIDs
(Table 5). Aspirin (100 mg/kg BID PO) has been rec-
ommended in cattle.98
Doses of flunixin in ruminants
are similar to the horse. Phenylbutazone (2–6 mg/kg IV
or PO) has a prolonged elimination half-life in cattle,
ranging from 30 to 82 hours;99,100
to avoid the presence
of residues that are toxic to humans, the FDA prohibits
its use in dairy cattle 20 months of age or older.
Ketoprofen (3 mg/kg) is effective in 4–8-week-old
calves for reducing pain from dehorning, after oral ad-
ministration.101
In 8–16-week-old calves, IV adminis-
tration of ketoprofen in conjunction with lidocaine
injection of the testicles for castration, blocked the
cortisol response.102
In sheep, carprofen (0.7 mg/kg IV) resulted in plasma
concentrations of 1.5 mg/mL, similar to those necessary
for analgesia in horses, for up to 48 hours; however,
analgesia was not assessed in this study.103
Non-traditional methods
Acupuncture and electro-acupuncture have been used
to provide visceral and cutaneous analgesia in research
and clinical settings.104–106
In conclusion, better pain management can be pro-
vided with the use of current available analgesic drugs
by more selective routes of administration (epidural,
intra-articular, transdermal patch), by methods that
maintain more steady plasma concentrations (CRIs),
and with the combination of different pharmacological
analgesic groups and techniques rather than single-
drug usage. Understanding the drugs’ mechanism and
site of action is important in selecting the best individ-
ual drug or combination of drugs for specific pain sit-
uations where relief is necessary for short to extended
periods of time without compromising the animal’s
well being. Special attention should be given to possible
adverse effects of these drugs and doses should be ad-
justed to the patient’s needs when different pharmaco-
logical groups are combined.
References
1. Alexander R, El-Moalem HE, Gan TJ. Comparison of the mor-
phine-sparing effects of diclofenac sodium and ketorolac
tromethamine after major orthopedic surgery. J Clin Anesth
2002; 14:187–192.
2. Taylor PM, Pascoe PJ, Mama KR. Diagnosing and treating pain in
the horse. Where are we today? Vet Clin Equine 2002; 18:1–19.
3. Price J. Behaviour-based assessment of equine pain: a quest for
objectivity, In: Proceedings of the Spring Meeting of the Associ-
ation of Veterinary Anaesthetists. Pain Assessment and Pain
Control. The Netherlands: Doorwerth; 2003, pp. 28–30.
4. Grant C, Upton RN, Kuchel TR. Efficacy of intra-muscular
analgesics for acute pain in sheep. Aus Vet J 1996; 73:129–132.
5. Molony V, Kent JE. Assessment of acute pain in farm animals
using behavioral and physiological measurements. J Anim Sci
1997; 75:266–272.
6. Price J, Marques JM, Welsh EM, et al. Pilot epidemiological study
of attitudes towards pain in horses. Vet Rec 2002; 151:570–575.
7. Kalpravidh M, Lumb WV, Wright M, et al. Analgesic effects of
butorphanol in horses: dose–response studies. Am J Vet Res 1984;
45:211–216.
304

8. Sellon DC, Monroe VL, Roberts MC, et al. Pharmacokinetics and
adverse effects of butorphanol administered by single intrave-
nous injection or continuous intravenous infusion in horses. Am J
Vet Res 2001; 62:183–189.
9. Steffey EP, Eisele JH, Baggot D. Interactions of morphine and
isoflurane in horses. Am J Vet Res 2003; 64:166–175.
10. Mathews NS, Lindsay SL. Effect of low-dose butorphanol on ha-
lothane minimum alveolar concentration in ponies. Equine Vet J
1990; 22:325–327.
11. Doherty TJ, Geiser DR, Rohrbach BW. Effect of acepromazine and
butorphanol on halothane minimum alveolar concentration in
ponies. Equine Vet J 1887; 29:374–376.
12. Kamerling S, Wood T, DeQuick D, et al. Narcotic analgesics, their
detection and pain measurement in the horse: a review. Equine
Vet J 1989; 21:4–12.
13. Doherty TJ, Geiser DR, Rohrbach BW. Effect of high volume
epidural morphine, ketamine and butorphanol on halothane
minimum alveolar concentration in ponies. Equine Vet J 1997; 29:
370–373.
14. Mircica E, Clutton RE, Kyles KW, et al. Problems associated with
perioperative morphine in horses: a retrospective case analysis.
Vet Anaesth Analg 2003; 30:147–155.
15. George LW. Pain control in food animals, In: Steffey EP. ed. Re-
cent Advances in Anesthetic Management of Large Domestic
Animals. Ithaca, NY: International Veterinary Information Service
2003, A0615.1103. Accessed March 1, 2004.
16. Pinheiro Machado LC, Hurnik JF, Ewing KK. A thermal thresh-
old assay to measure the nociceptive response to morphine
sulphate in cattle. Can J Vet Res 1998; 62:218–223.
17. Doherty TJ, Rohrbach BW, Geiser DR. Effect of acepromazine and
butorphanol on isoflurane minimum alveolar concentration in
goats. J Vet Pharmacol Therap 2002; 25:65–67.
18. Waterman AE, Livingston A, Amin A. Analgesic activity and
respiratory effects of butorphanol in sheep. Res Vet Sci 1991;
51:19–33.
19. Waterman AE, Livingston A, Amin A. Further studies on the
antinociceptive activity and respiratory effects of buprenorphine
in sheep. J Vet Pharmacol Therap 1991; 14:230–234.
20. Nolan A, Livingston A, Waterman AE. Investigation of the an-
tinociceptive activity of buprenorphine in sheep. Br J Anaesth
1987; 92:527–533.
21. Waterman AE, Livingston A, Amin A. Analgesia and respiratory
effects of fentanyl in sheep. J Assoc Vet Anaesth 1990; 17:20–23.
22. Nolan A, Waterman AE, Livingston A. The correlation of the
thermal and mechanical antinociceptive activity of pethidine hy-
drochloride with plasma concentrations of the drug in sheep.
J Vet Pharmacol Therap 1988; 11:94–102.
23. Carroll GL, Booth DM, Hartsfield SM, et al. Pharmacokinetics
and pharmacodynamics of butorphanol in llamas after intrave-
nous and intramuscular administration. J Am Vet Med Assoc
2001; 219:1263–1267.
24. Valverde A, Little CB, Dyson DH, et al. Use of epidural morphine
to relieve pain in a horse. Can Vet J 1990; 31:211–212.
25. Natalini CC, Robinson EP. Evaluation of the analgesic effects
of epidurally administered morphine, alfentanil, butorphanol,
tramadol, and U50488H in horses. Am J Vet Res 2000; 61:
1579–1586.
26. Pablo LS. Epidural morphine in goats after hindlimb orthopedic
surgery. Vet Surg 1993; 22:307–310.
27. Hendrickson DA, Kruse-Elliot KT, Broadstone RV. A comparison
of epidural saline, morphine, and bupivacaine for pain relief after
abdominal surgery in goats. Vet Sur 1996; 25:83–87.
28. Sysel AM, Pleasant SR, Jacobson JD. Efficacy of an epidural
combination of morphine and detomidine in alleviating exper-
imentally induced hindlimb lameness in horses. Vet Surg 1996;
25:511–518.
29. Goodrich LR, Nixon AJ, Fubini SL, et al. Epidural morphine and
detomidine decreases postoperative hindlimb lameness in horses
after bilateral stifle arthroscopy. Vet Surg 2002; 31:232–239.
30. Skarda RT, Muir WW. Caudal analgesia induced by epidural or
subarachnoid administration of detomidine hydrochloride solu-
tion in mares. Am J Vet Res 1994; 55:670–680.
31. Solomon RE, Gebhart GF. Synergistic antinociceptive interactions
among drugs administered to the spinal cord. Anesth Analg
1994; 78:1164–1172.
32. Ossipov MH, Harris S, Lloyd P, et al. Antinociceptive interaction
between opioids and medetomidine: systemic additivity and
spinal synergy. Anesthesiology 1990; 73:1227–1235.
33. Valverde A, Dyson DH, McDonell WN. Epidural morphine re-
duces halothane MAC in the dog. Can J Anaesth 1989; 36:
629–632.
34. Sysel AM, Pleasant RS, Jacobson JD, et al. Systemic and local
effects associated with long-term epidural catheterization and
morphine-detomidine administration in horses. Vet Surg 1997;
26:141–149.
35. Maxwell LK, Thomasy SM, Slovis N, et al. Pharmacokinetics of
fentanyl following intravenous and transdermal administration
in horses. Equine Vet J 2003; 35:484–490.
36. Wegner K, Long MT, Robertson SA. How to use fentanyl trans-
dermal patches for analgesia in horses. In: Proceedings of the
48th Annual AAEP Convention, Vol. 48. Orlando, FL, 4–8
December 2002, pp. 291–294.
37. Carroll GL, Hooper RN, Boothe DM, et al. Pharmacokinetics of
fentanyl after intravenous and transdermal administration in
goats. Am J Vet Res 1999; 60:986–991.
38. Sheehy JG, Hellyer PW, Sammonds GE, et al. Evaluation of op-
ioid receptors in synovial membranes of horses. Am J Vet Res
2001; 62:1408–1412.
39. Day TK, Pepper WT, Tobias TA, et al. Comparison of intra-
articular and epidural morphine for analgesia following stifle
arthrotomy in dogs. Vet Surg 1995; 24:522–530.
40. Reuben SS, Sklar J, El-Mansouri M. The preemptive analgesic
effect of intraarticular bupivacaine and morphine after ambula-
tory arthroscopic knee surgery. Anesth Analg 2001; 92:923–926.
41. Sammarco JL, Conzemius MG, Perkowski SZ, et al. Postoperative
analgesia for stifle surgery: a comparison of intra-articular
bupivacaine, morphine, or saline. Vet Surg 1996; 25:59–69.
42. Grndahl-Nielsen C, Simonsen HB, Damkjer Lund J, et al.
Behavioural, endocrine and cardiac responses in young calves
undergoing dehorning without and with use of sedation and
analgesia. Vet J 1999; 158:14–20.
43. Skarda RT. Local and regional anesthetic and analgesic tech-
niques, In: Thurmon JC, Tranquilli WJ, Benson GJ. eds.
LumbJone’s Veterinary Anesthesia. Baltimore, MD: Williams
Wilkins; 1996, pp. 426–514.
44. Doherty TJ, Frazier DL. Effect of intravenous lidocaine on halo-
thane minimum alveolar concentration in ponies. Equine Vet J
1998; 30:300–303.
45. Meyer GA, Lin HC, Hanson RR, et al. Effects of intravenous
lidocaine overdose on cardiac electrical activity and blood pres-
sure in the horse. Equine Vet J 20001; 33:434–437.
46. Valverde A, Doherty TJ, Hernández J, et al. Effect of lidocaine on
the minimum alveolar concentration of isoflurane in dogs. Vet
Anaesth Analg 2004; 31:264–271.
47. Schelling CG, Klein LV. Comparison of carbonated lidocaine and
lidocaine hydrochloride for caudal epidural anesthesia in horses.
Am J Vet Res 1985; 46:1375–1377.
48. Skarda RT, Muir WW. Analgesic, hemodynamic and respiratory
effects of caudal epidurally administered ropivacaine hydrochlo-
ride in mares. Vet Anaesth Analg 2001; 28:61–74.
49. Skarda RT. Techniques of local analgesia in ruminants and swine.
Vet Clin N A Food Anim Pract 1986; 2:621–663.
50. Tendillo FJ, Pera AM, Mascias A, et al. Cardiopulmonary and
analgesic effects of epidural lidocaine, alfentanil, and xylazine in
pigs anesthetized with isoflurane. Vet Surg 1995; 24:73–77.
51. Shafford HL, Hellyer PW, Turner AS. Intra-articular lidocaine
plus bupivacaine in sheep undergoing stifle arthrotomy. Vet
Anaesth Analg 2004; 31:20–26.
52. Jochle W, Moore JN, Brown J, et al. Comparison of detomidine,
butorphanol, flunixin meglumine and xylazine in clinical cases of
colic. Equine Vet J 1989; 20:331–334.
53. Moens Y, Lanz F, Doherr MG, et al. A comparison of the anti-
nociceptive effects of xylazine, detomidine and romifidine on
experimental pain in horses. Vet Anaesth Analg 2003; 30:183–190.

54. Brunson DB, Majors LJ. Comparative analgesia of xylazine,
xylazine/morphine, xylazine/butorphanol, and xylazine/nalbu-
phine in the horse, using dental dolorimetry. Am J Vet Res 1987;
48:1087–1091.
55. Nolan AM, Hall LW. Combined use of sedatives and opiates in
horses. Vet Rec 1984; 114:63–67.
56. Muir WW, Skarda RT, Sheehan WC. Hemodynamic and respira-
tory effects of xylazine-morphine sulfate in horses. Am J Vet Res
1979; 40:1417–1420.
57. Bettschart-Wolfensberger R, Clarke KW, Vainio O, et al. Phar-
macokinetics of medetomidine in ponies and elaboration of a
medetomidine infusion regime which provides a constant level of
sedation. Res Vet Sci 1999; 67:41–46.
58. Neges K, Bettschart-Wolfensberger R, Müller J, et al. The isoflu-
rane sparing effect of a medetomidine constant rate infusion in
horses. Vet Anaesth Analg 2003; 30:93–94.
59. Bennett RC, Steffey EP. The influence of morphine on the halo-
thane sparing effect of xylazine. In: Proceedings of the 6th
International Congress of Veterinary Anesthesiology, Greece,
Thessaloniki, 23–27 September 1997, p. 129.
60. Steffey EP, Pascoe PJ, Woliner MJ, et al. Effects of xylazine hy-
drochloride during isoflurane-induced anesthesia in horses. Am J
Vet Res 2000; 61:1225–1231.
61. Celly CS, McDonell WN, Young SS, et al. The comparative hypo-
xaemic effect of four a2 adrenoceptor agonist (xylazine, romifi-
dine, detomidine and medetomidine) in sheep. J Vet Pharmacol
Ther 1997; 20:464–471.
62. DeMoor A, Desmet P. Effect of Rompun on acid base equilibrium
and arterial oxygen pressure in cattle. Vet Med Rev 1971; 2:
163–169.
63. Kumar A, Thurmon JC. Cardiopulmonary, hemocytologic and
biochemical effects of xylazine in goats. Lab Anim Sci 1979;
29:486–491.
64. LeBlanc MM, Hubbell AE, Smith HC. The effects of xylazine hy-
drochloride on intrauterine pressure in the cow. Theriogenology
1984; 21:681–690.
65. Jansen CA, Lowe KC, Nathaielsz PW. The effect of xylazine on
intrauterine activity, fetal and maternal oxygenation, cardiovas-
cular function and fetal breathing. Am J Obstet Gynecol 1984;
148:386–390.
66. Waldridge BM, Lin HC, DeGraves FJ, et al. Sedative effects of
medetomidine and its reversal by atipamezole in llamas. J Am
Vet Med Assoc 1997; 211:1562–1565.
67. Wittern C, Hendrickson DA, Trumble T, et al. Complications
associated with administration of detomidine into the caudal
epidural space in a horse. J Am Vet Med Assoc 1998; 213:
516–518.
68. LeBlanc PH, Caron JP. Clinical use of epidural xylazine in the
horse. Equine Vet J 1990; 22:180–181.
69. Skarda RT, Muir WW. Analgesic, hemodynamic, and respiratory
effects of caudal epidurally administered xylazine hydrochloride
solution in mares. Am J Vet Res 1996; 57:193–200.
70. Doherty TJ, Geiser DR, Rohrbach BW. The effect of epidural
xylazine on halothane minimum alveolar concentration in
ponies. J Vet Pharmacol Ther 1997; 20:246–248.
71. Prado ME, Streeter RN, Mandsager RE, et al. Pharmacologic ef-
fects of epidural versus intramuscular administration of detomi-
dine in cattle. Am J Vet Res 1999; 60:1242–1247.
72. St.Jean G, Skarda RT, Muir WW, et al. Caudal epidural analgesia
induced by xylazine administration in cows. Am J Vet Res 1990;
51:1232–1236.
73. Chevalier HM, Provost PJ, Karas AZ. Effect of caudal epidural
xylazine on intraoperative distress and post-operative pain in
Holstein heifers. Vet Anaesth Analg 2004; 31:1–10.
74. Lin HC, Trachte EA, DeGraves FJ, et al. Evaluation of analgesia
induced by epidural administration of medetomidine to cows.
Am J Vet Res 1998; 59:162–167.
75. Ko JCH, Thurmon JG, Benson JG, et al. Evaluation of analgesia
induced by epidural injection of detomidine or xylazine in swine.
J Vet Anaesth 1992; 19:56–60.
76. Eide PK. Wind-up and the NMDA receptor complex from a clin-
ical perspective. Eur J Pain 2000; 4:5–17.
77. Kronenberg RH. Ketamine as an analgesic: parenteral, oral, rec-
tal, subcutaneous, transdermal, and intranasal administration.
J Pain Pall Care Pharm 2002; 16:27–35.
78. Muir WW III, Sams R. Effects of ketamine infusion on halothane
minimal alveolar concentration in horse. Am J Vet Res 1992; 53:
1802–1806.
79. Wagner AE, Walton JA, Hellyer PW, et al. Use of low doses of
ketamine administered by constant rate infusion as an adjunct for
postoperative analgesia in dogs. J Am Vet Med Assoc 2002;
221:72–75.
80. Gómez de Segura IA, De Rossi R, Santos M, et al. Epidural in-
jection of ketamine for perineal analgesia in the horse. Vet Surg
1998; 27:384–391.
81. Lee I, Yoshiuchi T, Yamagishi N, et al. Analgesic effect of caudal
epidural ketamine in cattle. J Vet Sci 2003; 4:261–264.
82. MacCallister CG. Comparison of adverse effects of phenylbuta-
zone, flunixin meglumine, and ketoprofen in horses. J Am Vet
Med Assoc 1993; 202:71–77.
83. Collins LG, Tyler DE. Phenylbutazone toxicosis in the horse: a
clinical study. J Am Vet Med Assoc 1984; 184:689–703.
84. Snow DH, Douglas TA, Thompson H, et al. Phenylbutazone tox-
icosis in equidae: a biochemical and pathophysiologic study. Am
J Vet Res 1981; 42:1754–1759.
85. Raekallio M, Taylor PM, Bennett RC. Preliminary investigations
of pain and analgesia assessment in horses administered phe-
nylbutazone or placebo after arthroscopic surgery. Vet Surg 1997;
26:150–155.
86. Crisman MV, Wilcke JR, Sams RA. Pharmacokinetics of flunixin
meglumine in healthy foals less than twenty-four hours old. Am J
Vet Res 1996; 57:1759–1761.
87. Coakley M, Peck KE, Taylor TS, et al. Pharmacokinetics of flu-
nixin meglumine in donkeys, mules, and horses. Am J Vet Res
1999; 60:1441–1444.
88. Matthews NS, Peck KE, Taylor TS, et al. Pharmacokinetics of
phenylbutazone and its metabolite oxyphenbutazone in minia-
ture donkeys. Am J Vet Res 2001; 62:673–675.
89. Mealey K, Matthews N, Peck KE, et al. Comparative pharmaco-
kinetics of phenylbutazone and its metabolite oxyphenbutazone
in clinically normal horses and donkeys. Am J Vet Res 1997;
58:53–55.
90. Mathews NS, Mealey KL, Peck KE, et al. Pharmacokinetics of
carprofen in donkeys: comparison to horses. In: Proceedings of
the 8th World Congress of Veterinary Anesthesia, Knoxville,
Tennessee, 16–20 September 2003, p. 133.
91. Owens J, Kamerling S, Barker S. Pharmacokinetics of ketoprofen
in healthy horses and horses with acute synovitis. J Vet Pharma-
col Ther 1995; 18:187–195.
92. Wilcke JR, Crisman MV, Scarratt WK, et al. Pharmacokinetics of
ketoprofen in healthy foals less than twenty-four hours old. Am J
Vet Res 1998; 59:290–292.
93. Verde CR, Simpson MI, Frigoli A, et al. Enantiospecific phar-
macokinetics of ketoprofen in plasma and synovial fluid of hors-
es with acute synovitis. J Vet Pharmacol Ther 2001; 24:179–185.
94. Armstrong S, Tricklebank P, Lake A, et al. Pharmacokinetics of car-
profen enantiomers in equine plasma and synovial fluid- a com-
parison with ketoprofen. J Vet Pharmacol Ther 1999; 22:196–201.
95. Goodrich LR, Furr Robertson, Warnick LD. A toxicity study of
eltenac, a nonsteroidal anti-inflammatory drug, in horses. J Vet
Pharmacol Ther 1998; 21:24–33.
96. Lees P, May SA, Hoeijmakers M, et al. A pharmacodynamic and
pharmacokinetic study with vedaprofen in an equine model of
acute nonimmune inflammation. J Vet Pharmacol Ther 1999;
22:96–106.
97. Sinclair M, Mealey KL, Mathews NS, et al. The pharmacokinetics
of meloxicam in horses. In: Proceedings of the 8th World Con-
gress of Veterinary Anesthesia, Knoxville, Tennessee, 16–20 Sep-
tember 2003, p. 112.
98. Gingerich DA, Baggot JD, Yeary RA. Pharmacokinetics and dos-
age of aspirin in cattle. J Am Vet Med Assoc 1975; 167:945–948.
99. DeBacker P, Braeckman R, Belpaire F. Bioavailability and
pharmacokintetics of phenylbutazone in the cow. J Vet Pharma-
col Ther 1980; 3:29–33.
306

100. Arifah AK, Lees P. Pharmacodynamics and pharmacokinetics of
phenylbutazone in calves. J Vet Pharmacol Ther 2002; 25:299–309.
101. Faulkner PM, Weary DM. Reducing pain after dehorning in dairy
calves. J Dairy Sci 2000; 83:2037–2041.
102. Stafford KJ, Mellor DJ, Todd SE, et al. Effects of local anaesthesia
or local anaesthesia plus a non-steroidal anti-inflammatory drug
on the acute cortisol response of calves to five different methods
of castration. Res Vet Sci 2002; 73:61–70.
103. Welsh EM, Baxter P, Nolan AM. Pharmacokinetics of carprofen
administered intravenously to sheep. Res Vet Sci 1992; 53:
264–266.
104. Skarda RT, Muir WW III. Comparison of electroacupuncture and
butorphanol on respiratory and cardiovascular effects and rectal
pain threshold after controlled rectal distention in mares. Am J
Vet Res 2003; 64:137–144.
105. Skarda RT, Tejwani GA, Muir WW. Cutaneous analgesia, hemo-
dynamic and respiratory effects, and b-endorphin concentration
in spinal fluid and plasma of horses after acupuncture and per-
cutaneous acupoint electrical stimulation. Am J Vet Res 2002;
63:1435–1442.
106. Zhu GQ. Electroacupuncture treatment of 100 equine cases with
colic. Chin J Vet Med 1979; 11:28–30.

Oski 5.pdf

Recommended

Recommended

More Related Content

Similar to Oski 5.pdf

Similar to Oski 5.pdf (20)

More from leroleroero1

More from leroleroero1 (20)

Recently uploaded

Recently uploaded (20)

Oski 5.pdf