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CHAPTER 4. Effective pain management
This chapter presents an overview of the basic clinical strategies used to
manage pain in laboratory animals with particular attention to both
pharmacologic and non-pharmacologic methods. Special themes include
preventive analgesia, consequences of unrelieved pain, and ethical
considerations relating to pain as a subject of study. Available information on
pain management of non-mammalian species is also presented.
Introduction
The regulatory review process (see Appendix B) requires that
investigators adequately control pain in research animals, unless procedures
that may cause more than momentary or slight pain are justified for scientific
reasons and approved by the IACUC. In order to treat or prevent pain, it is
necessary to evaluate its source and intensity (for additional discussion see
Chapter 3). As a rule, pain is likely to occur as a result of tissue injury in
proportional terms, that is more extensive tissue damage results in greater pain
and thus a need for a stronger analgesic regimen. While certain conditions
reliably cause severe pain (e.g., acute nerve compression, burns, spastic
contraction of smooth muscle) and inflammation often contributes to the
worsening of pain, we have an incomplete understanding of how much pain to
expect in various animal species. Information about the cause and effect of
surgery or disease and pain in clinical veterinary medicine is largely based on
observation and anecdote and tends to focus on commonly treated species,
such as dogs, cats, and horses. Table 1-1 of Chapter 1 lists examples of
typically painful conditions that occur either spontaneously or as a result of
experimental procedure.
Clinical veterinary pain management
The principles of clinical veterinary pain management and prevention,
summarized in Boxes 4-1 and 4-2 and elaborated upon in this chapter and in
other parts of this report, are comparatively easy to apply in clinically familiar
species such as dogs and cats, for which ranges of doses and drug combinations
are better known. Readers are encouraged to seek publications (including the
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74 Recognition and Alleviation of Pain in Laboratory Animals
American College of Veterinary Anesthesiologists’ Position Paper on the
Treatment of Pain 1998), reports, books, and handouts within the veterinary
literature for explicit information on available drugs, doses, routes of
administration, side effects, contraindications, and the like useful for dogs,
cats, rabbits and other pets often used as research animals. However, the
application of the principles discussed below to other laboratory animal species
is a matter of trial and error until such time as adequate scientific information
is available to establish evidence-based guidelines, including information on
the feasibility of various routes of administration (e.g., oral bioavailability,
palatability, transdermal preparations).
Box 4-1 Current guidelines for clinical veterinary pain management
Sedation does not provide pain relief and may mask the animal’s response
to pain
Use of analgesic and adjunct drugs should be at effective plasma/tissue
concentrations especially when the nociceptive barrage and pain are
greatest (i.e., after surgery or injury)
Use of more than one type of management strategy (e.g., multimodal
analgesia-targeting multiple pain mechanisms with the use of local
anesthetics and opioids, or using anxiolytics when post-surgical pain is likely
to be moderate to severe) is recommended
Avoidance of peaks and valleys in analgesic dosing when postsurgical pain is
expected to be severe (this is best accomplished by the administration of
continuous or overlapping regimes) maintains animal well-being
Monitoring of effectiveness (i.e., assessment at appropriate intervals) of
analgesics administered is crucial
If there is doubt about the source of an animal’s clinical signs,
administration of an additional dose of analgesic helps determine whether
pain was the cause
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CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 75
Box 4-2 Additional considerations for the prevention and management of
pain in laboratory animals
Pain in animals is often unrecognized and under-treated.
If a procedure is considered painful in humans, it should be assumed to be
painful in laboratory animals, regardless of their age or species.
Adequate treatment of pain may be associated with decreased
complications, lower mortality, reduced variability in experimental data,
and improved scientific outcomes.
The appropriate use of environmental, non-pharmacological, or
pharmacological interventions, as well as the selection of humane endpoints
in animal experimentation, can prevent or reduce animal pain in most
experimental designs without compromising the scientific validity of the
research, except in situations where pain is the subject of research.
Researchers, veterinarians, and animal care professionals should be
responsible for learning about the assessment, prevention, and management
of pain in laboratory animals.
Veterinarians and animal care professionals should develop IACUC-approved
educational guidelines and protocols for the management of pain in
laboratory animals at their institution.
Some ranges for effective doses of analgesics in rats and mice (i.e.,
doses that reduce experimental measures of pain and/or reach tissue
concentrations believed to be effective in other species) are available through
literature search. However, strain differences in animals’ responses to
analgesics and anesthetics are an important factor to consider (Mogil et al.
2005; Terner et al. 2003; Wilson et al. 2003a, b).
Strategies for managing pain in laboratory animals
Effective management of pain in laboratory animals often begins with
general (surgical) anesthesia, but also includes local anesthetics, analgesics,
anxiolytics, and sedatives as well as non-pharmacological methods (including
minimization of tissue trauma). Pain management goals range from total
elimination of pain as, for example, during general anesthesia for a surgical
procedure, to pain that is tolerated without compromising the animal’s well-
being.
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76 Recognition and Alleviation of Pain in Laboratory Animals
General anesthesia
When animals are anesthetized for procedures that would otherwise
cause pain, it is important to maintain an appropriate depth of anesthesia. A
wide range of indices have been developed to assess depth of anesthesia in
animals and humans (Appadu and Vaidya 2008; Bruhn et al. 2006; Franks 2008;
John and Prichep 2005; Lu et al 2008; Murrell and Johnson 2006; Otto 2008;
Whelan and Flecknell 1992); these include autonomic responses such as
changes in heart rate and blood pressure, alterations in the EEG or other
measures of CNS function, or changes in somatic reflex responses to noxious
stimuli. During anesthesia not accompanied by neuromuscular blocking agents,
depression of somatic reflex responses is the most widely used method for
ensuring an appropriate depth of anesthesia. In all animal species, absence of
the pedal withdrawal reflex indicates a surgical plane of anesthesia (i.e.,
anesthesia that is deep enough to eliminate the experience of pain and thus
allow surgery to take place). Although this is an easily assessed index, it is
important to use a stimulus that is sufficiently noxious but not so strong as to
produce tissue damage. In some species, other reflexes, such as the response
to applying a clamp to the nasal septum (pigs) or pinching the ears (rabbit,
guinea pig), are also useful but reliance on these responses has been criticized
(Antognini et al. 2005) because animals may lose consciousness at much lighter
anesthesia planes, in which case the persistence of reflexes would not indicate
pain perception (see also Box 1-3 in Chapter 1). Doses of anesthetic agents
sufficient to suppress spinal reflexes may therefore be greater than those
required to carry out surgery humanely; if these reflexes are not suppressed,
surgery will be hampered by the animals’ repeated reflex movements.
Although the use of neuromuscular blocking agents (i.e., agents that prevent
neurotransmiters from acting on their receptors in skeletal muscles) could
prevent such movements, it would also require intubation and mechanical
ventilation of the animal. For practical reasons, suppression of withdrawal
responses remains the most useful means of ensuring loss of both awareness
and responses to surgical stimuli.
The ideal general anesthetic should rapidly and/or smoothly induce
muscle relaxation and a surgical plane of anesthesia, and it should be readily
controllable and reversible. There are two categories of general anesthetics
used in laboratory animal medicine: volatile inhalants (e.g., isoflurane) and
injectable drugs (e.g., barbiturates, other sedative-hypnotic agents such as
propofol, or combinations of drugs such as propofol-fentanyl). The later
category also includes total intravenous anesthesia (TIVA). TIVA techniques
may be useful in laboratory animal settings where the equipment required for
inhalant anesthesia is not practical or possible (e.g., near MRI units). Other
injectable general anesthetic drugs still in use due to their unique application
in specialized studies include -chloralose, tribromoethanol, and urethane.
These drugs have certain specific applications but may not be appropriate for
situations in which animals will recover (Gaertner et al. 2008; Karas and
Silverman 2006; Koblin 2002; Meyer and Fish 2005). After surgery, with
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CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 77
anesthetic withdrawal and recovery, animals will experience pain unless
controlled by analgesics.
Sedation/anxiolysis
Sedatives and anxiolytics are adjuncts to general anesthetics and are
also used in pain management strategies. These two distinct classes of drugs
are often used in combination to modulate, block, or relieve pain. Terminology
varies but a general distinction between the sedative-hypnotic agents and
anxiolytics is often useful. Sedative-hypnotic drugs (e.g., barbiturates and
drugs with significant sedating properties such as 2-adrenoceptor agonists)
produce dose-dependent states of CNS depression that vary from somnolence
to general anesthesia and even death. Anxiolytics include drugs that reduce
anxiety or fear (e.g., benzodiazepines) and can induce sleep. Some anxiolytic
drugs, previously termed “tranquilizers” (e.g., phenothiazines like
acepromazine and butyrophenones like haloperidol and droperidol), produce a
state of relaxation and indifference to external stimuli and, in elevated doses,
can induce an undesirable cataleptic state rather than general anesthesia. Of
the above drugs and classes, only the 2-adrenoceptor agonists have analgesic
efficacy. Neither barbiturates nor anxiolytics are analgesic; barbiturates may
in fact contribute to a hyperalgesic state, while phenothiazines and
butyrophenones are generally considered devoid of analgesic efficacy. Readers
are referred to the section “Modulatory influences on pain: Anxiety, fear, and
stress” in Chapter 2 for in-depth discussion on the relationship of anxiety and
pain.
Neuroleptanalgesia is an intense analgesic and amnesic state produced
by the combination of an opioid analgesic and a neuroleptic drug (this
description is adapted from the American Heritage Medical Dictionary 2007).
The neuroleptic drug component is a phenothiazine or butyrophenone (or an
anxiolytic) and the analgesic is a potent and efficacious opioid that acts as a
major tranquilizer (i.e., anxiolytic). Butorphanol-acepromazine, fentanyl-
fluanisone (Hypnorm), and oxymorphone-midazolam are examples of
commonly used veterinary neuroleptanalgesic combinations.
Neuroleptanalgesic combinations by themselves are not sufficient for most
surgical interventions. However, the use of drugs with sedative or tranquilizing
properties (neurolepts as well as α2-adrenoceptor agonists) combined with
opioids, ketamine, or tiletamine-zolazepam (Telazol®) can achieve states
ranging from modified consciousness (e.g., reduction of anxiety or “conscious
sedation”) to complete unconsciousness (general anesthesia). Table 4-1
summarizes the analgesic properties of selected drugs, including common
tranquilizers, sedatives and anesthetics, used in laboratory animals.
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78 Recognition and Alleviation of Pain in Laboratory Animals
Table 4-1 Analgesic properties of selected anesthetic drugs and
adjuncts
Drug Class Analgesic
efficacy
α2-adrenoceptor Analgesic/sedative-hypnotic Yes
agonists
Βarbiturates Sedative-hypnotic No
Βenzodiazepines anxiolytic No
Butyrophenones Neuroleptic/anxiolytic No
Chloralose, chloral Sedative-hypnotic No
hydrate
Ketamine Dissociative, NMDA antagonist Yes
Halogenated inhalant General anesthetic No
anesthetics
Opioids
Analgesic Yes
Nitrous oxide General anesthetic (human); general Yes
anesthetic adjunct only in animals
Phenothiazines Neuroleptic/anxiolytic No
Propofol Sedative-hypnotic No
Tiletamine-zolazepam Combination of a dissociative/ NMDA Yes
(Telazol®) receptor antagonist and a
benzodiazepine anxiolytic
Tribromoethanol Sedative-hypnotic No
Urethane (i.e., ethyl Not classified No
carbamate)
Note: Drugs with inherent analgesic effects may contribute to postoperative
pain control but are not sufficient to exert such control in and of themselves.
Analgesia
Conventional analgesic drug classes include opioids, NSAIDs, and local
anesthetics. Although analgesia is defined as “lack of pain”, complete
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CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 79
elimination of pain in awake animals is commonly neither achievable nor
desirable. Pain has a protective role in that it usually serves to limit further
injury; for example, in humans with no skin sensation prone to undetectable
injury or infection. But in some instances animals with untreated severe pain
may struggle or self-mutilate and cause or exacerbate additional injury to
themselves. With most analgesic techniques, however, residual pain naturally
limits activity, although it is not a restraint mechanism and should not be used
to restrain animals.
The goal of analgesic drug intervention is to achieve a balanced state
during which an animal is neither substantially hindered by pain nor adversely
affected by the side effects of analgesics. Often the use of a single analgesic is
sufficient. An emerging practice for the prevention or treatment of established
pain in both human and veterinary patients, however, is the combined use of
two or more types of analgesics or “multimodal analgesia” (Buvanendron and
Kroin 2007; Corletto 2007; Hellyer et al. 2007; Kehlet et al. 2006; Lemke 2004;
White 2005; White et al. 2007). Multimodal postsurgical analgesia may be
regarded as overly complicated, but cited benefits include more effective and
efficient analgesia and possible dose reduction of one or more individual drugs.
In theory, treatment of patients with non-opioid analgesics to reduce the
overall requirement for opioids would result in fewer opioid-induced side
effects. The concept, known as “opioid sparing”, is a desirable goal because
extended or high-dose opioid therapy is often accompanied by unwanted side
effects (e.g., sedation, constipation, urinary retention, or analgesic tolerance)
that prolong or complicate convalescence (Kehlet 2004; White et al. 2007).
Synergy (i.e., greater analgesia than predicted from a simple additive effect of
the combination of two drugs acting with different mechanisms) has been
demonstrated in numerous experimental animal models (e.g., Price et al. 1996;
Kolesnikov et al. 2000; Matthews and Dickenson 2002; Qiu et al. 2007) as well
as with combinations of opioids, NSAIDs, local anesthetics, alpha2-agonists,
ketamine, tramadol, and gabapentin (Guillou et al. 2003; Koppert et al. 2004;
Reuben and Buvanendran 2007; White et al. 2007). Multimodal analgesia using
“adjuvant analgesics” (i.e., antidepressants, antiepileptic drugs, NMDA
antagonists, or transdermal lidocaine) may also be an effective alternative for
the treatment of refractory chronic pain unresponsive to the administration of
a single agent (Knotkova and Pappagallo 2007). Table 4-2 summarizes various
pharmacologic methods for treating pain of various intensities.
Advanced analgesic techniques
The ability to provide analgesia to laboratory animals is limited by the
lack of information about species-specific drug effects and doses. It is perhaps
useful to understand the state-of-the-art techniques currently used in clinical
(i.e., non-laboratory) veterinary medicine as a potential objective for
laboratory animal pain medicine; identification of the most useful techniques
may lead to important innovations to help overcome barriers to the provision of
analgesia. Needless to say, size, species, and technical aspects will continue
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80 Recognition and Alleviation of Pain in Laboratory Animals
to be limiting factors for many techniques. Box 4-2 provides a summary of
analgesic techniques and their limitations.
Table 4-2 Pharmacologic approach to pain management based
upon predicted intensity
Pain Analgesic approach
intensity
Low Single-agent therapy acceptable
NSAIDs, local anesthetic infiltration, or opioid agonist-antagonists (butorphanol,
buprenorphine)
Moderate Multimodal analgesia to be considered
NSAIDs in combination with adjuncts such as local anesthetics, opioid agonist-
antagonists (buprenorphine),tramadol, alpha-2 agonists, NMDA antagonists
High Multimodal analgesia recommended
mu-opioid agonists (morphine, hydromorphone, fentanyl, methadone) + one or
more of the following: NSAIDs, local anesthetics, alpha-2 agonists, antiepileptic
drugs, NMDA antagonists
Advanced analgesic techniques – epidural administration of local anesthetics +/-
opioids and constant rate infusions
BOX 4-2 Advanced analgesic techniques
Low-dose epidural administration of opioids or opioid-local anesthetic
combinations can result in analgesia whose quality is similar to if not better
than that achieved with systemic administration. This method depends on
technical expertise and may be challenging to implement in very small animals.
Epidural administration of drugs has not been studied in non-mammalian
vertebrates.
Local anesthetics can be injected into joints, wounds, and body cavities
(abdominal or pleural) by continuous or intermittent injection through intra-
wound catheters, greatly reducing the need for systemic administration of
other analgesics (Liu et al. 2006). The relatively short duration of the action of
local anesthetics may limit their utility in situations where redosing is difficult.
Lidocaine is used intravenously to provide analgesia after tissue injury (Omote
2007).
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CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 81
Oral administration of some analgesics is feasible (e.g., NSAIDs, opioids,
gabapentin), but for some drugs (opioids) first-pass (species dependent)
metabolism limits bioavailability, necessitating dose adjustment, use of a
different route of administration, or selection of another drug. Compounding
of drugs into palatable forms that animals are willing to consume is possible,
but without data to support a particular method, one must be concerned about
absorption, shelflife, or efficacy.
Dilution of injectable analgesics to make them easier to use or to
improve precision in very small animals must be done with the understanding
that formulations may not work as well and that shelf life is not predictable.
Continuous infusion of certain types of analgesics (e.g., opioids,
ketamine, alpha2-adrenoreceptor agonists) avoids ‘peaks and valleys’ in drug
concentration and may provide better coverage for moderate to severe pain.
Transdermal preparations are available in formulations suitable for larger
animals and may be useful in producing uninterrupted analgesia. Sustained-
release formulations make it possible to avoid periods of inadequate drug
administration. For further consultation please see Carroll 2008; Flecknell
2009; Gaynor and Muir 2008; Hellyer et al. 2007; Krugner-Higby et al. 2008;
Lamont and Mathews 2007; Robertson 2005; Tranquilli et al. 2007; Valdeverde
and Gunkel 2005.
Non-pharmacologic methods
Non-pharmacologic approaches to pain management are appropriate
when the use of pharmacological methods is contraindicated, effective
analgesic drugs are not available, or they can complement drug therapy. Non-
pharmacologic methods include preventive strategies that help minimize
causative factors for pain, through, for example, appropriate animal handling
and minimization of tissue trauma during surgery. Such techniques are
important because both long-duration surgery and extensive tissue
manipulation (e.g., extensive rib retraction, prolonged tourniquet-induced limb
ischemia, disproportionately long incision relative to animal size) result in
increased postoperative pain. Training in proper surgical techniques coupled
with knowledge of comparative anatomy is necessary to appreciate the distinct
needs of each animal species pre-, during, and post-surgery so that the 3Rs
principle of refinement is upheld. Moreover, nonphysiologic restraint or
surgical positioning of animals may exert undue pressure on joints, nerves, or
soft tissues and cause significant post-procedural pain. These sources of pain
are avoidable if investigators and animal care personnel are trained to
understand that any form of tissue pressure, damage, ischemia is a potential
cause of pain (Martini et al. 2000; LASA 1990). Minimally invasive surgery
techniques (e.g., fiberoptic technologies) further reduce tissue injury and are
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82 Recognition and Alleviation of Pain in Laboratory Animals
associated with reduced postsurgical pain, stress response, and convalescence
time compared to open or scalpel surgery (reviewed by Karas et al. 2008).
Methods for the prevention or management of pain
While classic pharmacologic treatment requires drugs with specific
analgesic properties, unconventional drugs, such as antiepileptics, can also be
effective. And, when anxiety contributes to pain, drugs with anxiolytic
properties can be added.
Analgesics
A comprehensive review of the effects and doses of analgesic drugs is
beyond the scope of this work (for comprehensive reviews see Carpenter 2001;
Carroll 2008; Flecknell and Waterman-Pearson 2000; Gaynor and Muir 2008;
Hawk et al. 2005; Lamont and Mathews 2007; Robertson 2005; Valverde and
Gunkel 2005). Instead, this section provides a general overview of analgesic
drugs that are currently used or may become useful in laboratory animal
medicine.
Opioids
Opioid analgesics are important drugs for surgical analgesia and/or
therapeutic management of moderate to severe pain in humans and certain
animal species. There are two general categories of such analgesics (Ross et
al. 2006; Stefano et al. 2005; Waldhoer et al. 2004): opioid receptor agonists
(e.g., morphine, hydromorphone, fentanyl) and mixed opioid receptor
agonist/antagonists (e.g., buprenorphine, butorphanol); the latter group
possess (in a single molecule) agonist efficacy at one of the three types of
opioid receptor and antagonist efficacy at a different opioid receptor.
A third group of endogenous opioid peptides (e.g., endorphins,
enkephalins and dynorphins) are produced by the body and also act on opioid
receptors. It is a misconception, however, to assume that the only role of
endogenous opioid peptides is to produce analgesia; they have multiple,
nonanalgesic functions depending on where in the body they are produced and
released. Given the existence of three distinct opioid receptors, all located in
variable densities in various tissues, differences in the selectivity and affinity
of opioid drugs and endogenous opioid peptides are believed to account for
many of the variations in the effect profile of opioids (Fields 2004; Waldoer et
al. 2004). And bcause opioid receptors are subject to regulation (e.g., by
phosphorylation or endocytosis), the effects of both endogenous and exogenous
opioids can be influenced by the ‘state’ of the receptor. Changes such as these
presumably account for the phenomenon of analgesic tolerance, a reduction in
the analgesic effectiveness of a given dose of drug after repeated
administration.
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CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 83
Opioids are the most efficacious analgesics available, but their use is
accompanied by undesirable effects that include an increase in smooth muscle
tone and reduction in propulsive motility of the gastrointestinal tract (leading
to constipation), cough suppression, respiratory depression, behavioral changes
(euphoria and dysphoria, excitement or increased locomotion in horses and
rodents), and physiological dependence. In addition to their presence on
neurons both in the nociceptive pathway (see Chapter 2) and elsewhere in the
body (e.g., gastrointestinal tract), opioid receptors are found on cells of the
immune system and opioid effects on immune function vary from stimulation to
inhibition (Stefano et al. 2005; Page 2005). In rats and other rodents, pica
(eating large volumes of food and nonedible substances, such as bedding) has
been noted with the use of the partial opioid receptor agonist/weak antagonist
buprenorphine (Aung et al. 2004; Bosgraaf et al. 2004; Clark et al. 1997;
Yamamoto et al. 2004). Concern about the undesirable side effects of opioids
is frequently cited as a reason for not using them. However, for limited or
short-term therapy, the side effects are often either manageable or not a
problem.
Dose regimens of opioid analgesics for dogs, cats, horses, rats, mice, a
few species of birds, and sheep have been reported. When such regimens are
based on experimental evidence, that evidence frequently derives from an
analgesiometric testing method (such as thermal threshold; Johnson et al.
2007; Robertson et al. 2005a, b; Waterman et al. 1991; Wilson et al. 2003a,b).
Doses for other mammals currently listed in formularies are based on
extrapolation; however, relatively little is known about the efficacy, drug
choices, or side effects of opioids in amphibians, reptiles, invertebrates, and
most birds.
In addition to classical intravenous, intramuscular, and intraperitoneal
routes of administration, many opioids are also substantially bioavailable by
nasal, sublingual, or rectal routes (Lindhardt et al. 2000; Robertson et al.
2005a). Oral administration of opioids in mammals often diminishes their
bioavailability making this method of delivery less effective. Additionally,
long-duration formulations of opioids have been investigated in animal models
and, although not yet commercially available, may represent a future method
to provide sustained analgesia in laboratory animals (Krugner-Higby et al. 2008;
Smith et al. 2004). Because of the relative safety of opioids, additional work to
determine effective dose ranges and novel methods of administration is needed
for most laboratory animal species.
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Krugner-Higby L, Smith L, Clark M, Heath TD, Dahly E, Schiffman B, Hubbard-
VanStelle S, Ney D, Wendland A. 2003. Liposome-encapsulated
oxymorphone hydrochloride provides prolonged relief of postsurgical
visceral pain in rats. Comp Med 53(3):270-279.
Kuan CY, Roth KA, Flavell RA, Rakic P. 2000. Mechanisms of programmed cell
death in the developing brain. Trends Neurosci 23(7):291-297.
KuKanich B, Papich MG. 2004. Pharmacokinetics of tramadol and the
metabolite O-desmethyltramadol in dogs. J Vet Pharmacol Ther
27(4):239-246.
Kuwahara RT, Skinner RB. 2001. EMLA versus ice as a topical anesthetic.
Dermatol Surg 27(5):495-496.
LASA [Laboratory Animal Science Association]. 1990. The assessment and
control of the severity of scientific procedures on laboratory animals.
Report of the Laboratory Animal Science Association Working Party. Lab
Anim 24(2):97-130.
Lagerweij E, Nelis PC, Wiegant VM, van Ree JM. 1984. The twitch in horses: A
variant of acupuncture. Science 225(4667):1172-1174.
Lamont L, Mathews K. 2007. Opioids, non-steroidal anti-inflammatories, and
analgesic adjuvants. In: Lumb and Jones' Veterinary Anesthesia and
Analgesia. Tranquilli WJ, Thurmon JC, Grimm KA, Lumb WV, eds. Ames,
Iowa: Blackwell Publishing.
Lascelles BD, Court MH, Hardie EM, Robertson SA. 2007. Nonsteroidal anti-
inflammatory drugs in cats: a review. Vet Anaesth Analg 34(4):228-250.
Lascelles BD, Cripps PJ, Jones A, Waterman AE. 1997. Post-operative central
hypersensitivity and pain: The pre-emptive value of pethidine for
ovariohysterectomy. Pain 73(3):461-471.
Lascelles BD, Waterman AE, Cripps PJ. Livingston A, Henderson G. 1995.
Central sensitization as a result of surgical pain: Investigation of the pre-
emptive value of pethidine for ovariohysterectomy in the rat. Pain
62(2);201-212.
Laule GE, Bloomsmith MA, Schapiro SJ. 2003. The use of positive reinforcement
training techniques to enhance the care, management, and welfare of
primates in the laboratory. J Appl Anim Welf Sci 6(3):163-173.
Leece EA, Brearley JC, Harding EF. 2005. Comparison of carprofen and
meloxicam for 72 hours following ovariohysterectomy in dogs. Vet
Anaesth Analg 32(4):184-192.
Lees P. 2003. Pharmacology of drugs used to treat osteoarthritis in veterinary
practice. Inflammopharmacology 11(4):385-399.
Lees P, Giraudel J, Landoni MF, Toutain PL. 2004. PK-PD integration and PK-PD
modelling of nonsteroidal anti-inflammatory drugs: Principles and
applications in veterinary pharmacology. J Vet Pharmacol Ther
27(6):491-502.
Lemaire L, van der Poll T. 2007. Immunomodulatory effects of general
anesthetics. In: Intensive Care Medicine: Annual Update 2007. Vincent J-
L, ed. New York: Springer. p 208-216.
Prepublication Copy
OCR for page 115
CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 115
Liles JH, Flecknell PA, Roughan J, Cruz-Madorran I. 1998. Influence of oral
buprenorphine, oral naltrexone or morphine on the effects of
laparotomy in the rat. Lab Anim 32(2):149-161.
Lindhardt K, Ravn C, Gizurarson S, Bechgaard E. 2000. Intranasal absorption of
buprenorphine--in vivo bioavailability study in sheep. Int J Pharm 205(1-
2):159-163.
Linton SJ. 2000. A review of psychological risk factors in back and neck pain.
Spine 25(9):1148-1156.
Liu SS, Richman JM, Thirlby RC, Wu CL. 2006. Efficacy of continuous wound
catheters delivering local anesthetic for postoperative analgesia: A
quantitative and qualitative systematic review of randomized controlled
trials. J Am Coll Surg 203(6):914-932.
Loepke AW, Priestley MA, Schultz SE, McCann J, Golden J, Kurth CD. 2002.
Desflurane improves neurologic outcome after low-flow cardiopulmonary
bypass in newborn pigs. Anesthesiology 97(6):1521-1527.
Loepke AW, Soriano SG. 2008. An assessment of the effects of general
anesthetics on developing brain structure and neurocognitive function.
Anesth Analg 106(6):1681-707.
Lu Y, Vera-Portocarrero LP, Westlund KN. 2003. Intrathecal coadministration of
D-APV and morphine is maximally effective in a rat experimental
pancreatitis model. Anesthesiology 98(3):734-740.
Luger NM, Sabino MA, Schwei MJ, Mach DB, Pomonis JD, Keyser CP, Rathbun M,
Clohisy DR, Honore P, Yaksh TL, Mantyh PW. 2002. Efficacy of systemic
morphine suggests a fundamental difference in the mechanisms that
generate bone cancer vs inflammatory pain. Pain 99(3):397-406.
Luhmann J, Hurt S, Shootman M, Kennedy R. 2004. A comparison of buffered
lidocaine versus ELA-Max before peripheral intravenous catheter
insertions in children. Pediatrics 113(3 Pt 1):e217-e220.
Lussier D, Huskey AG, Portenoy RK. 2004. Adjuvant analgesics in cancer pain
management. Oncologist 9(5):571-591.
Lynch JJ 3rd, Wade CL, Zhong CM, Mikusa JP, Honore P. 2004. Attenuation of
mechanical allodynia by clinically utilized drugs in a rat chemotherapy-
induced neuropathic pain model. Pain 110(1-2):56-63.
Ma D, Williamson P, Januszewski A, Nogaro MC, Hossain M, Ong LP, Franks NP,
Maze M. 2007. Xenon mitigates isoflurane-induced neuronal apoptosis in
the developing rodent brain. Anesthesiology 106(4):746-753.
Machin KL. 2001. Fish, amphibian, and reptile analgesia. Vet Clin North Am
Exot Anim Pract 4(1):19-33.
Machin KL, Tellier LA, Lair S, Livingston A. 2001. Pharmacodynamics of flunixin
and ketprofen in Mallard ducks (Anas Platyrhynchos). J Zoo Wild Med
32(2):222-229.
Malavasi LM, Nyman G, Augustsson H, Jacobson M, Jensen-Waern M. 2006.
Effects of epidural morphine and transdermal fentanyl analgesia on
physiology and behaviour after abdominal surgery in pigs. Lab Anim
40(1):16-27.
Prepublication Copy
OCR for page 116
116 Recognition and Alleviation of Pain in Laboratory Animals
Martini L, Lorenzini RN, Cinotti S, Fini M, Giavaresi G, Giardino R. 2000.
Evaluation of pain and stress levels of animals used in experimental
research. J Surg Res 88(2):114-119.
Martucci C, Panerai AE, Sacerdote P. 2004. Chronic fentanyl or buprenorphine
infusion in the mouse: Similar analgesic profile but different effects on
immune responses. Pain 110(1-2):385-392.
Mattei P, Rombeau JL. 2006. Review of the pathophysiology and management
of postoperative ileus. World J Surg 30(8):1382-1391.
Matthews EA, Dickenson AH. 2002. A combination of gabapentin and morphine
mediates enhanced inhibitory effects on dorsal horn neuronal responses
in a rat model of neuropathy. Anesthesiology 96(3):633-640.
Matthiesen T, Wohrmann T, Coogan TP, Uragg H. 1998. The experimental
toxicology of tramadol: An overview. Toxicol Lett 95(1):63-71.
McAuliffe JJ, Joseph B, Vorhees CV. 2007. Isoflurane-delayed preconditioning
reduces immediate mortality and improves striatal function in adult
mice after neonatal hypoxia-ischemia. Anesth Analg 104(5):1066-1077,
tables of contents.
Mc Geown D, Danbury TC, Waterman-Pearson AE, Kestin SC. 1999. Effect of
caprofen on lamenss in broiler chickens. Vet Rec 144:668-671.
McMillan FD. 2003. A world of hurts--is pain special? J Am Vet Med Assoc
223(2):183-186.
Medhurst SJ, Walker K, Bowes M, Kidd BL, Glatt M, Muller M, Hattenberger M,
Vaxelaire J, O'Reilly T, Witherspoon G, Winter J, Green J, Urban L. 2002.
A rat model of bone cancer pain. Pain 96(1-2):129-140.
Meyer R, Fish R. 2008. Pharmacology of injectable anesthetics, sedatives, and
tranquilizers. In: Anesthesia and Analgesia in Laboratory Animals. Fish R,
Brown M, Danneman P, Karas A, eds. San Diego: Academic Press. p 27-
83.
Meyer RE, Fish RE. 2005. A review of tribromoethanol anesthesia for production
of genetically engineered mice and rats. Lab Anim (NY) 34(10):47-52.
Millecamps M, Etienne M, Jourdan D, Eschalier A, Ardid D. 2004. Decrease in
non-selective, non-sustained attention induced by a chronic visceral
inflammatory state as a new pain evaluation in rats. Pain 109(3):214-
224.
Miranda HF, Puig MM, Prieto JC, Pinardi G. 2006. Synergism between
paracetamol and nonsteroidal anti-inflammatory drugs in experimental
acute pain. Pain 121(1-2):22-28.
Mogil JS, Smith SB, O'Reilly MK, Plourde G. 2005. Influence of nociception and
stress-induced antinociception on genetic variation in isoflurane
anesthetic potency among mouse strains. Anesthesiology 103(4):751-758.
Mohan S, Stevens CW. 2006. Systemic and spinal administration of the mu
opioid, remifentanil, produces antinociception in amphibians. Eur J
Pharmacol 534(1-3):89-94.
Morley S, Eccleston C, Williams A. 1999. Systematic review and meta-analysis
of randomized controlled trials of cognitive behaviour therapy and
Prepublication Copy
OCR for page 117
CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 117
behaviour therapy for chronic pain in adults, excluding headache. Pain
80(1-2):1-13.
Mosley CA. 2005. Anesthesia and analgesia in reptiles. Semin Avian Exot Pet
Medic 14(4):243-262.
Mosley CA, Dyson D, Smith DA. 2003. Minimum alveolar concetration of
isoflurane in green iguanas and the effect of butorphanol on minimum
alveolar concetration. J Am Vet Med Assoc 222(11):1559-1564.
Mosley CA, Dyson D, Smith DA. 2004. The cardiovascular dose-response effects
of isoflurane alone and combined with butorphanol in the green
iguana(Iguana iguana). Vet Anaesth Analg 31(1):64-72.
Muir WW, Wiese AJ, March PA. 2003. Effects of morphine, lidocaine, ketamine,
and morphine-lidocaine-ketamine drug combination on minimum
alveolar concentration in dogs anesthetized with isoflurane. Am J Vet
Res 64(9):1155-1160.
Mulcahy DM, Tuomi P, Larsen RS. 2003. Differential mortality of male
spectacled eiders (Somateria fischeri) and kind eiders (Somateria
spectabilis) subsequent to anesthesia with propofol, bupivacaine, and
ketoprofen. J Avian Med Surg 17(3):117-123.
Munro G, Erichsen HK, Mirza NR. 2007. Pharmacological comparison of
anticonvulsant drugs in animal models of persistent pain and anxiety.
Neuropharmacology 53(5):609-618.
Murrell JC, Hellebrekers LJ. 2005. Medetomidine and dexmedetomidine: A
review of cardiovascular effects and antinociceptive properties in the
dog. Vet Anaesth Analg 32(3):117-127.
Murrell JC, Johnson CB. 2006. Neurophysiological techniques to assess pain in
animals. J Vet Pharmacol Ther 29(5):325-335.
Newby NC, Mendonca PC, Gamperl K, Stevens ED. 2006. Pharmacokinetics of
morphine in fish: winter flounder (Pseudopleuronectes americanus) and
seawater-acclimated rainbow trout (Oncorhynchus mykiss). Comp
Biochem Physiol C Toxicol Pharmacol 143(3):275-283.
Nishimaki H, Fukuda S, Ishimoto M, Mori Y, Eguchi H, Kokubun S, Fujihara H,
Watanabe H, Abo T. 2002. Isoflurane ameliorates the posthypoxic
deoxygenation of the rat brain--the role of cell adhesion molecules of
polymorphonuclear leukocytes. Resuscitation 54(2):207-214.
Nordgreen J, Horsberg TE, Ranheim B, Chen C. 2007. Somatosensory evoked
potentials in the telencephalon of Atlantic salmon (Salmo salar)
following galvanic stimulation of the tail. J Comp Physiol A. 193:1235-
1242.
Omote K. 2007. Intravenous lidocaine to treat postoperative pain management:
Novel strategy with a long-established drug. Anesthesiology 106(1):5-6.
Ong EL, Lim NL, Koay CK. 2000. Towards a pain-free venipuncture. Anaesthesia
55(3):260-262.
Otto KA. 2008. EEG power spectrum analysis for monitoring depth of
anaesthesia during experimental surgery. Lab Animals 42:45-61.
Padgett DA, Glaser R. 2003. How stress influences the immune response.
Trends Immunol 24(8):444-448.
Prepublication Copy
OCR for page 118
118 Recognition and Alleviation of Pain in Laboratory Animals
Page GG, Blakely WP, Ben-Eliyahu S. 2001. Evidence that postoperative pain is
a mediator of the tumor-promoting effects of surgery in rats. Pain 90(1-
2):191-199.
Paul-Murphy JR, Brunson DB, Miletic V. 1999. Analgesic effects of butorphanol
and buprenorphine in conscious African grey parrots (Psittacus erithacus
and Psittacus erithacus timneh). Am J Vet Res 60(10):1218-1221.
Peart JN, Gross ER, Gross GJ. 2005. Opioid-induced preconditioning: Recent
advances and future perspectives. Vascul Pharmacol 42(5-6):211-218.
Perkins FM, Kehlet H. 2000. Chronic pain as an outcome of surgery: A review of
predictive factors. Anesthesiology 93(4):1123-1133.
Ploghaus A, Narain C, Beckmann CF, Clare S, Bantick S, Wise R, Matthews PM,
Rawlins JN, Tracey I. 2001. Exacerbation of pain by anxiety is associated
with activity in a hippocampal network. J Neurosci 21(24):9896-9903.
Pogatzki-Zahn EM, Zahn PK. 2006. From preemptive to preventive analgesia.
Curr Opin Anaesthesiol 19(5):551-555.
Post H, Heusch G. 2002. Ischemic preconditioning: Experimental facts and
clinical perspective. Minerva Cardioangiol 50(6):569-605.
Price DD, Mao J, Lu J, Caruso FS, Frenk H, Mayer DJ. 1996. Effects of the
combined oral administration of NSAIDs and dextromethorphan on
behavioral symptoms indicative of arthritic pain in rats. Pain 68(1):119-
127.
Qiu HX, Liu J, Kong H, Liu Y, Mei XG. 2007. Isobolographic analysis of the
antinociceptive interactions between ketoprofen and paracetamol. Eur J
Pharmacol 557(2-3):141-146.
Read MR. 2004. Evaluation of the use of anesthesia and analgesia in reptiles.
JAVMA 227:547-552.
Reichert JA, Daughters RS, Rivard R, Simone DA. 2001. Peripheral and
preemptive opioid antinociception in a mouse visceral pain model. Pain
89(2-3):221-227.
Reilly SC, Quinn JP, Cossins AR, Sneddon LU. 2008a. Novel candidate genes
identified in the brain during nociception in common carp. Neuro Sci
Letts 437:135-138.
Reilly SC, Quinn JP, Cossins AR, Sneddon LU. 2008b. Behavioural analysis of a
nociceptive event in fish: Comparisons between three species
demonstrate specific responses. Appl Anim Behav Sci 114(1-2): 248-259.
Rennie AE, Buchanan-Smith HM. 2006. Refinement of the use of non-human
primates in scientific research. Part I: The influence of humans. Anim
Welf 15(3):203-213.
Reuben SS, Buvanendran A. 2007. Preventing the development of chronic pain
after orthopaedic surgery with preventive multimodal analgesic
techniques. J Bone Joint Surg Am 89(6):1343-1358.
Richebe P, Rivat C, Laulin JP, Maurette P, Simonnet G. 2005. Ketamine
improves the management of exaggerated postoperative pain observed
in perioperative fentanyl-treated rats. Anesthesiology 102(2):421-428.
Prepublication Copy
OCR for page 119
CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 119
Riess ML, Stowe DF, Warltier DC. 2004. Cardiac pharmacological
preconditioning with volatile anesthetics: From bench to bedside? Am J
Physiol Heart Circ Physiol 286(5):H1603-1607.
Robertson SA. 2005. Assessment and management of acute pain in cats. J Vet
Emerg Crit Care 15(4):261-272.
Robertson SA, Lascelles BD, Taylor PM, Sear JW. 2005a. PK-PD modeling of
buprenorphine in cats: Intravenous and oral transmucosal
administration. J Vet Pharmacol Ther 28(5):453-460.
Robertson SA, Taylor PM, Sear JW, Keuhnel G. 2005b. Relationship between
plasma concentrations and analgesia after intravenous fentanyl and
disposition after other routes of administration in cats. J Vet Pharmacol
Ther 28(1):87-93.
Romanovsky AA. 2004. Signaling the brain in the early sickness syndrome: Are
sensory nerves involved? Front Biosci 9:494-504.
Romero-Sandoval EA, Horvath RJ, DeLeo JA. 2008. Neuroimmune interactions
and pain: Focus on glial-modulating targets. Curr Opin Investig Drugs
9:726-734.
Rose JD. 2002. The neurobehavioral nature of fishes and the question of
awareness and pain. Rev Fish Sci 10(1):1-38.
Ross JR, Riley J, Quigley C, Welsh KI. 2006. Clinical pharmacology and
pharmacotherapy of opioid switching in cancer patients. Oncologist
11(7):765-773.
Roughan JV, Flecknell PA. 2001. Behavioural effects of laparotomy and
analgesic effects of ketoprofen and carprofen in rats. Pain 90(1-2):65-
74.
Roughan JV, Flecknell PA. 2004. Behaviour-based assessment of the duration of
laparotomy-induced abdominal pain and the analgesic effects of
carprofen and buprenorphine in rats. Behav Pharmacol 15(7):461-472.
Sacerdote P, Bianchi M, Gaspani L, Manfredi B, Maucione A, Terno G,
Ammatuna M, Panerai AE. 2000. The effects of tramadol and morphine
on immune responses and pain after surgery in cancer patients. Anesth
Analg 90(6):1411-1414.
Sakai H, Sheng H, Yates RB, Ishida K, Pearlstein RD, Warner DS. 2007.
Isoflurane provides long-term protection against focal cerebral ischemia
in the rat. Anesthesiology 106(1):92-99; discussion 98-10.
Samad TA, Moore KA, Sapirstein A, Billet S, Allchorne A, Poole S, Bonventre JV,
Woolf CJ. 2001. Interleukin-1 beta-mediated induction of Cox-2 in the
CNS contributes to inflammatory pain hypersensitivity. Nature 410:471-
475.
Samad TA, Sapirstein A, Woolf CJ. 2002. Prostanoids and pain: Unraveling
mechanisms and revealing therapeutic targets. Trends Mol Med 8(8):390-
396.
Sasamura T, Nakamura S, Iida Y, Fujii H, Murata J, Saiki I, Nojima H, Kuraishi Y.
2002. Morphine analgesia suppresses tumor growth and metastasis in a
mouse model of cancer pain produced by orthotopic tumor inoculation.
Eur J Pharmacol 441(3):185-191.
Prepublication Copy
OCR for page 120
120 Recognition and Alleviation of Pain in Laboratory Animals
Schipke JD, Kerendi F, Gams E, Vinten-Johansen J. 2006. Postconditioning: A
brief review. Herz 31(6):600-606.
Schneemilch CE, Hachenberg T, Ansorge S, Ittenson A, Bank U. 2005. Effects of
different anaesthetic agents on immune cell function in vitro. Eur J
Anaesthesiol 22(8):616-623.
Shäfers M, Marziniak M, Sorkin LS, Yaksh TL, Sommer C. 2004. Cyclo-oxygenase
inhibition in nerve injury- and TNF-induced hyperalgesia in the rat. Exp
Neurol 185(1):160-168.
Shaiova L. 2006. Difficult pain syndromes: Bone pain, visceral pain, and
neuropathic pain. Cancer J 12(5):330-340.
Shavit Y, Fish G, Wolf G, Mayburd E, Meerson Y, Yirmiya R, Beilin B. 2005. The
effects of perioperative pain management techniques on food
consumption and body weight after laparotomy in rats. Anesth Analg
101(4):1112-1116.
Sladky KK, Krugner-Higby L, Meek-Walker E, Heath TD, Paul-Murphy J. 2006.
Serum concentrations and analgesic effects of liposome-encapsulated
and standard butorphanol tartrate in parrots. Am J Vet Res 67(5):775-
781.
Slikker W, Jr., Zou X, Hotchkiss CE, Divine RL, Sadovova N, Twaddle NC, Doerge
DR, Scallet AC, Patterson TA, Hanig JP, Paule MG, Wang C. 2007.
Ketamine-induced neuronal cell death in the perinatal rhesus monkey.
Toxicol Sci 98(1):145-158.
Smith LJ, Krugner-Higby L, Trepanier LA, Flaska DE, Joers V, Heath TD. 2004.
Sedative effects and serum drug concentrations of oxymorphone and
metabolites after subcutaneous administration of a liposome-
encapsulated formulation in dogs. J Vet Pharmacol Ther 27(5):369-372.
Sneddon LU. 2002. Anatomical and electrophysiological analysis of the
trigeminal nerve in a teleost fish, Oncorhynchus mykiss. Neuroscience
Letters 319(3):167-171.
Sneddon LU. 2003. The evidence for pain in fish: The use of morphine as an
analgesic. Appl Anim Behav Sci 83(2):153-162.
Sneddon LU. 2003. Trigeminal somatosensory innervation of the head of a
teleost fish with particular reference to nociception. Brain Res 972(1-
2):44-52.
Sneddon LU. 2004. Evolution of nociception in vertebrates: comparative
analysis of lower vertebrates. Brain Res Brain Res Rev 46(2):123-130.
Sneddon LU. 2006. Ethics and welfare: Pain perception in fish. B Eur Assoc Fish
Path 26(1):6-10.
Sneddon LU, Braithwaite VA, Gentle MJ. 2003a. Do fishes have nociceptors?
Evidence for the evolution of a vertebrate sensory system. Proc R Soc
Lond B Biol Sci 270(1520):1115-1121.
Sneddon LU, Braithwaite VA, Gentle MJ. 2003b. Novel object test: Examining
nociception and fear in the rainbow trout. Journal of Pain 4(8):431-440.
Soriano SG, Anand KJS, Rovnaghi CR, Hickey PR. 2005. Of mice and men: Should
we extrapolate rodent experimental data to the care of human
neomates? Anesthesiology 102:866-868.
Prepublication Copy
OCR for page 121
CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 121
Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S, Hoeft A, Stuber F. 2003.
Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain
105(1-2):231-238.
Stefano GB, Fricchione G, Goumon Y, Esch T. 2005. Pain, immunity, opiate and
opioid compounds and health. Med Sci Monit 11(5):MS47-53.
Stevens CW. 2004. Opioid research in amphibians: An alternative pain model
yielding insights on the evolution of opioid receptors. Brain Res Brain Res
Rev 46(2):204-215.
Stevens CW, Klopp AJ, Facello JA. 1994. Analgesic potency of mu and kappa
opioids after systemic administration in amphibians. J Pharmacol Exp
Ther 269(3):1086-1093.
Stevens CW, MacIver DN, Newman LC. 2001. Testing and comparison of non-
opioid analgesics in amphibians. Contemp Top Lab Anim Sci 40(4):23-27.
Stoskopf MK. 1994. Pain and analgesia in birds, reptiles, amphibians, and fish.
Invest Ophthalmol Vis Sci 35(2):775-780.
Strigo IA, Duncan GH, Bushnell MC, Boivin M, Wainer I, Rodriguez Rosas ME,
Persson J. 2005. The effects of racemic ketamine on painful stimulation
of skin and viscera in human subjects. Pain 113(3):255-264.
Suleiman MS, Zacharowski K, Angelini GD. 2008. Inflammatory response and
cardioprotection during open-heart surgery: The importance of
anaesthetics. Br J Pharmacol 153(1):21-33.
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I, the
Memantine Study Group. 2004. Memantine treatment in patients with
moderate to severe Alzheimer disease already receiving donepezil: A
randomized controlled trial. JAMA 291:317-324.
Terner JM, Lomas LM, Smith ES, Barrett AC, Picker MJ. 2003. Pharmacogenetic
analysis of sex differences in opioid antinociception in rats. Pain
106(3):381-391.
Terril-Robb LA, Suckow MA, Grigdesby CF. 1996. Evaluation of the analgesic
effects of butorphanol tartrate, xylazine hydrochloride, and flunixin
meglumine in Leopard Frogs (Rana pipiens). Contemp Top Lab Anim
35(3):54-56.
Todd MM. 2004. Anesthetic neurotoxicity: The collision between laboratory
neuroscience and clinical medicine. Anesthesiology 101(2):272-273.
Tranquilli WJ, Thurmon JC, Grimm KA, Lumb WV, eds. 2007. Lumb and Jones'
Veterinary Anesthesia and Analgesia. Ames, Iowa: Blackwell Publishing.
Trnkova S. 2007. Effect of non-=steroidal anti-inflammatory drugs on the blood
profile in the green iguana (Iguana iguana). Veter Medic 11:507-511.
Tuttle AD, Papich M, Lewbart GA, Christian S, Gunkel C, Harms CA. 2006.
Pharmacokinetics of ketoprofen in the green iguana (Iguana iguana)
following single intravenous and intramuscular injections. J Zoo Wildl
Med 37(4):567-70.
Ulrich-Lai YM, Xie W, Meij JT, Dolgas CM, Yu L, Herman JP. 2006. Limbic and
HPA axis function in an animal model of chronic neuropathic pain.
Physiol Behav 88(1-2):67-76.
Prepublication Copy
OCR for page 122
122 Recognition and Alleviation of Pain in Laboratory Animals
Vallejo R, Hord ED, Barna SA, Santiago-Palma J, Ahmed S. 2003. Perioperative
immunosuppression in cancer patients. J Environ Pathol Toxicol Oncol
22(2):139-146.
Valverde A, Gunkel CI. 2005. Pain management in horses and farm animals. J
Vet Emerg Crit Car 15(4):295-307.
Visser E, Schug SA. 2006. The role of ketamine in pain management. Biomed
and Pharmacother 60:341-348.
Wagner KA, Gibbon KJ, Strom TL, Kurian JR, Trepanier LA. 2006. Adverse
effects of EMLA (lidocaine/prilocaine) cream and efficacy for the
placement of jugular catheters in hospitalized cats. J Feline Med Surg
8(2):141-144.
Waldhoer M, Bartlett SE, Whistler JL. 2004. Opioid receptors. Annu Rev
Biochem 73:953-990.
Wang L, Traystman RJ, Murphy SJ. 2008. Inhalational anesthetics as
preconditioning agents in ischemic brain. Curr Opin Pharmacol 8(1):104-
110.
Waterman AE, Livingston A, Amin A. 1991. Further studies on the
antinociceptive activity and respiratory effects of buprenorphine in
sheep. J Vet Pharmacol Ther 14(3):230-234.
Watkins LR, Maier SF. 2005. Immune regulation of central nervous system
functions: From sickness responses to pathological pain. J Intern Med
257(2):139-155.
Weber NC, Preckel B, Schlack W. 2005. The effect of anaesthetics on the
myocardium: New insights into myocardial protection. Eur J Anaesthesiol
22(9):647-657.
Weise KL, Nahata MC. 2005. EMLA for painful procedures in infants. J Pediatr
Health Care 19(1):42-47; quiz 48-49.
Whelan G, Flecknell PA. 1992. The assessment of depth of anaesthesia in
animals and man. Lab Anim 26(3):153-162.
White PF. 2005. The changing role of non-opioid analgesic techniques in the
management of postoperative pain. Anesth Analg 101(5 Suppl):S5-S22.
White PF, Kehlet H, Neal JM, Schricker T, Carr DB, Carli F. 2007. The role of
the anesthesiologist in fast-track surgery: From multimodal analgesia to
perioperative medical care. Anesth Analg 104(6):1380-1396.
Whiteside GT, Harrison J, Boulet J, Mark L, Pearson M, Gottshall S, Walker K.
2004. Pharmacological characterisation of a rat model of incisional pain.
Br J Pharmacol 141(1):85-91.
Willenbring S, Stevens CW. 1997. Spinal mu, delta and kappa opioids alter
chemical, mechanical and thermal sensitivities in amphibians. Life Sci
61(22):2167-2176.
Wilson SG, Bryant CD, Lariviere WR, Olsen MS, Giles BE, Chesler EJ, Mogil JS.
2003a. The heritability of antinociception II: Pharmacogenetic mediation
of three over-the-counter analgesics in mice. J Pharmacol Exp Ther
305(2):755-764.
Wilson SG, Smith SB, Chesler EJ, Melton KA, Haas JJ, Mitton B, Strasburg K,
Hubert L, Rodriguez-Zas SL, Mogil JS. 2003b. The heritability of
Prepublication Copy
OCR for page 123
CHAPTER 4: EFFECTIVE PAIN MANAGEMENT 123
antinociception: Common pharmacogenetic mediation of five
neurochemically distinct analgesics. J Pharmacol Exp Ther 304(2):547-
559.
Wolfensohn S. 2004. Social housing of large primates: Methodology for
refinement of husbandry and management. ATLA Altern Lab Anim
32(Suppl. 1A):149-151.
Woolf CJ. 1983. Evidence for a central component of postinjury pain
hypersensititivty. Nature 308:386-388.
Woolf CJ. 2007. Central sensitization: Uncovering the relation between pain
and plasticity. Anesthesiology 106:864-867.
Wright-Williams SL, Courade JP, Richardson CA, Roughan JV, Flecknell PA.
2007. Effects of vasectomy surgery and meloxicam treatment on faecal
corticosterone levels and behaviour in two strains of laboratory mouse.
Pain 130(1-2):108-118.
Xie Z, Dong Y, Maeda U, Moir RD, Xia W, Culley DJ, Crosby G, Tanzi RE. 2007.
The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis
and amyloid beta-protein accumulation. J Neurosci 27(6):1247-1254.
Yaksh TL, Dirig DM, Malmberg AB. 1998. Mechanism of action on non-steroidal
anti-inflammatory drugs. Cancer Investig 16(7):509-527.
Yoon WY, Chung SP, Lee HS, Park YS. 2008. Analgesic pretreatment for
antibiotic skin test: Vapocoolant spray vs ice cube. Am J Emerg Med
26(1):59-61.
Zhao P, Zuo Z. 2004. Isoflurane preconditioning induces neuroprotection that is
inducible nitric oxide synthase-dependent in neonatal rats.
Anesthesiology 101(3):695-703.
Prepublication Copy
OCR for page 124
