Lisa Johnson, BA, SRS, LATg

Certification Review Session

2010 ASR Annual Meeting
Clearwater Beach, FL
 What is Pain?

• Accepted definition:
– An unpleasant sensory (noxious) and
emotional experience associated with actual
or potential tissue damage
– Anything which would cause more than
momentary pain in humans, should be
assumed to cause pain in an animal
 Definitions

• Agology – the science and study of pain

• Allodynia – pain caused by a stimulus that is not normally
painful
• Analgesia – the absence, or decrease, of pain in the
presence of a stimulus that would normally be painful
• Hyperalgesia – an increased sensitivity to a stimulus that is
normally painful
• Nociception – the reception, conduction, and central
nervous processing of nerve signals resulting in the
perception of pain
• Somatic pain – pain originating from skin, joints, muscles,
and other deep tissues
• Visceral pain – pain originating from the internal organs
 Definitions

 Noxious stimulus – a stimulus which is actually or potentially

damaging to body tissues
 Pain threshold – the point at which an individual just begins
to feel pain; is relatively consistent among normal
individuals
 Pain tolerance – the greatest amount of pain that a subject
will tolerate; varies greatly among individuals
 Radiculalgia – pain along the distribution of one or more
sensory nerve roots
 Radiculitis – an inflammation of one or more nerve roots
 Wind-up – a cascade of events resulting from ongoing
stimulation of nociceptors and activation of NMDA
receptors; causes hyperalgesia and opioid tolerance
 Types of Pain

Physiological Pain Pathological Pain

• Is a protective  Results from tissue injury
mechanism  Inflammation occurs in the
area
• Causes avoidance
 Nerve damage
• Little to no tissue injury  Release of
• Pain stops once the neurotransmitters with
stimulus is removed ongoing stimulation of
nociceptors
 Can lead to hyperalgesia
 Persists after the stimulus is
removed
 Types of Pain

Acute Pain Chronic Pain

• Occurs immediately after  Persists well past initial
a stimulus is received stimulus (3-6 months)
• Severity can vary  Severity can vary
 May or may not respond
• Responds well to
well to treatment; may
treatment require a “multi-modal”
• Subsides once stimulus is approach
removed  Can result in allodynia,
hyperalgesia, and opioid
tolerance
 Physiology of Pain

• Damaged cells release • A-delta nociceptors are

substances which myelinated, conduct
stimulate nociceptors impulses rapidly, trigger
and inflammation sensation of first pain
(sharp, pricking pain)
• Noxious stimuli activate • C-fibers are
nociceptors, which unmyelinated,
become sensitized with stimulated by chemicals
stimulation, resulting in released in damaged or
a lowered stimulation inflamed tissues, and
threshold mediates slow, burning
pain
 Physiology of Pain

• Sensitized nociceptors • Afferent neurons in the

cause the release of spinal cord relay the
glutamate and signal to multiple areas
neurokinins from the in the brain, resulting in
afferent terminals in the
spinal cord the perception of pain
• Activates NMDA (N- • “Gate control” occurs in
methyl-D-asparate) the spinal cord,
receptors, which are resulting in early
implicated in inhibition of
hypersensitivity (wind- nociception, allowing
up) escape
 Physiology of Pain

• Stimulation of • Various
medulary centers neurotransmitters are
result in released: glutamate,
hyperventilation, norepinephrine,
increased cardiac serotonin, gamma-
aminobutyric acid
output, and increased
(GABA) and endorphins
blood pressure
• Analgesia can be
• Descending neurons induced by blocking the
act to modulate pain nociceptive process at
by reducing sensation one or more points
 Physiology of Pain

Pain ≠ Nociception
What is the difference?
Pain is a product of higher brain center processing of
signals it has received.
Nociception refers to the peripheral and central nervous
systems processing information generated by stimulation
of nociceptors by noxious stimuli
Nociception can occur in the absence of pain.
 Physiology of Pain

There are four distinct processes involved in

nociception which can be modulated by
analgesics:
– Transduction – translation of the noxious stimulus
into electrical activity at the peripheral nociceptor
– Transmission – the propagation of nerve
impulses through the nervous system
– Modulation – modification of nociceptive
transmission by inhibition of the spinal dorsal
horn cells by endorphins
– Perception – the final conscious subjective and
emotional experience of pain
 Actions of Analgesics on Pain
Processes

Transduction:
– Can be blocked by local anesthetics by injection either at the site
of injury/incision or intravenously
– Can be decreased by use of NSAIDs which decrease the
production of prostaglandins at the site of injury
Transmission:
– Can be prevented by local anesthetics by injection along
peripheral nerves, at nerve plexus, or in the epidural or
subarachnoid spaces
Modulation:
– Can be augmented by injection of local anesthetics or alpha2-
adrenergic agonists; gabapentin may also effect modulation
Perception:
– Altered by use of general anesthetics or systemic injection of
opioids and/or alpha2-agonists
 Actions of Analgesics on Pain
Processes

• Pre-emptive analgesia: giving analgesics prior

to the noxious stimulus (surgery)
– By blocking or inhibiting the nociceptive process
before it begins, hypersensitivity is prevented
– May decrease the amount of anesthesia and
post-operative analgesia needed
• Multimodal or “balanced” analgesia: using a
combination of analgesics which will impact
more than one portion of the nociceptive
process
– For example: buprenorphine and meloxicam pre-
surgically, lidocaine block used prior to incision,
and bupivicaine splash prior to closing incision
 Analgesics

• Divided into five main classes based on

mode of action
– Opioids
– Non-steroidal anti-inflammatory drugs
– Local anesthetics
– Alpha2-adrenoceptor agonists
– Miscellaneous drugs
 Analgesics - Opioids

• Bind to opioid receptor sites within CNS (mostly

µ but also κ)
• Are agonists, partial agonists or mixed agonists-
antagonists
• Are controlled substances requiring special
licenses and documentation of usage
 Opioids

• Agonists – include morphine and fentanyl

– Potent opioid analgesics
– Have more serious potential side effects than the
mixed agonist/antagonists: respiratory
depression, bradycardia, vomiting, constipation
– Can be used in a continuous infusion during
anesthesia
– Combined with tranquilizers for
neuroleptanalgesic balanced anesthesia
– Can be administered intravenously,
intramuscularly, via transdermal patches, and
epidurally +/- local anesthetics
– Can be reversed with naloxone
 Opioids

• Mixed agonist-antagonist – includes butorphanol

– Have agonist or partial agonist activity at one or more
opioid receptors and the ability to antagonize the
effects of a full agonist at one or more opioid receptor
– Butorphanol is a mu antagonist and kappa agonist
– Butorphanol isn’t routinely used for analgesia
currently due to it’s dosing frequency
– Less respiratory depression than full agonists
– Can be used post-operatively to reverse the narcosis
of fentanyl while still providing analgesia
– Has a “ceiling” effect, at which point increased doses
won’t have any further effect
 Opioids

• Partial Agonist – includes buprenorphine

– Has both agonist and antagonist activity at the
mu receptor
– Can be used to reverse pure mu agonists
– Buprenorphine has a prolonged duration of action
(relatively)
– Also potential for ceiling effect
 Non-steroidal Anti-inflammatory
Drugs (NSAIDs)

• NSAIDs are weak organic acids with anti-

inflammatory, analgesic, and antipyretic properties
• Inhibit prostaglandin production by inhibiting COX
enzymes
• Are either non-selective (inhibits both COX iso-
enzymes) or selective for COX-2
• Non-selective NSAIDs have more serious side
effects (gastric ulceration and renal toxicity)
• Decreased renal blood flow during anesthesia
makes kidneys more susceptible to toxic effects
• Carprofen and meloxicam are COX-2 selective
inhibitors which have a reasonable margin of safety
when used pre-operatively
 Local Anesthetics

• Decrease or prevent Na+ permeability of the

membrane of neurons, which stops the transfer
of signals along the peripheral nerves
• Prevent central sensitization since the
nociceptive signal is blocked
• Classified by duration of action
– Lidocaine is short acting with a rapid on-set
– Bupivicaine is long acting with a slow on-set
– Duration of action can be extended by adding a
vasoconstrictor like epinephrine
 Local Anesthetics

Multiple uses and routes of administration

• Topical: most are applied to mucous membranes but
some preparations will be absorbed through skin
– 0.5% proparacaine is recommended for examining eyes
– Lidocaine and benzocaine sprays are used to assist in
intubation (benzocaine has been implicated in
methemoglobinemia and should be used sparingly and
with caution)
– Xylocaine jell can be used to lubricate endotracheal tubes
and urinary catheters
– EMLA cream contains lidocaine and prilocaine and is used
to numb skin
 Local Anesthetics

• “Splash”
– Can apply to exposed tissues prior to closure and
nerves prior to transection during amputations
– “Soaker catheters”
• Infiltration
– Multiple intradermal or subcutaneous injections of
local anesthetic along proposed incision line
– May contain epinephrine (1:200,000) to increase
effect and duration
• Field block
– Used to anesthetize large areas
• Intradermal or SQ infiltration followed by injection
deeply enough to infiltrate nerves
 Local Anesthetics

• Regional blocks (nerve blocks)

– Injection into the connective tissue
surrounding a nerve
– Can produce loss of sensation and/or
paralysis in the region supplied by the nerve
– Requires smaller volumes than field blocks,
reducing the risk of toxicity
 Local Anesthetics

• Epidurals
– Administered alone or in combination with
other analgesics
– If combined, smaller doses can be used,
decreasing risks of adverse effects
– Can cause motor deficits at higher doses
 Alpha2-Adrenergic Agonists

• Stimulation of the alpha2 – adrenoceptors

result in sedation, muscle relaxation, and
analgesia
• Can be reversed with alpha2-adrenergic
antagonists such as yohimbine and
atipamezole
• Includes xylazine, medetomidine, and
detomidine
 Miscellaneous Analgesics

• Tramadol
– Synthetic opioid agonist which also inhibits serotonin and
norepiniphrine re-uptake in the spinal cord
– The main metabolite has moderate opioid activity
• Ketamine
– NMDA antagonist
– Used as a CRI during surgery at sub-anesthetic doses, it
reduces MAC and can help prevent hypersensitivity
– More effective treating somatic pain than visceral pain
– Can be administered via epidural injection
• Gabapentin
– Analogue of naturally occurring neurotransmitter GABA
– Believed to increase production of GABA
• Part of endogenous inhibition of nociception
– Used to treat nerve pain
 Pain Assessment

 In order to adequately relieve pain, you need to

be able to assess the presence of pain to know if
your analgesic regimen is working
 Need to be familiar with the species/strain you
are working with to be able to recognize normal
vs. abnormal behavior
 Signs of pain will vary not only between various
species, but between strains and individuals
within a species
 There is no single sign which will always indicate
a specific amount of pain universally
 Pain Assessment – Signs of Pain

 Lethargy  Abnormal posture

 Avoidance  Ruffled coat
 Biting/licking at injured  Decreased food/water
area consumption
 “Worried” expression  Decreased elimination
 Vocalization  Listlessness
 Disuse of limb  Hiding
 Aggression  “Inwardly” focused
 Hunched posture  Failure to make a nest
 “Writhing”  Disinterest in
environment
 Pain Assessment

• Physiological changes can occur:

– Increased heart rate
– Increased blood pressure
– Dilation of pupils
– Heat in the effected area
– Changes in respiration
– Increased cortisol levels
– Porphyrin staining around the eyes of rodents
 Pain Assessment – Analog
Scales

• Establish parameters to score as an indicator

of pain, determine what score will indicate
insufficient analgesia, and have a rescue plan
• Needs to be species specific
• If dealing with a socialized species, can be
used in conjunction with physiological
parameters such as heart rate, respiratory
rate, and/or blood pressure
Pain Assessment – Analog
Scales
 So What Do I Need To Know?

• Definitions
• Types of pain
• Pain pathway
• Types of analgesics and their action
• Pain assessment
 References

• Thurmon JC, Tranquilli WI, Benson GJ, eds.

Lumb and Jones’ Veterinary Anesthesia, 3rd
edition, Williams & Wilkins, Baltimore. 1996
• NRC, Recognition and Alleviation of Pain in
Laboratory Animals, The National Academies
Press, Washington, DC. 2009
• Flecknell PA and Waterman-Pearson A. Pain
Management in Animals, WB Saunders, London,
2000
• Flecknell PA, Laboratory Animal Anaesthesia,
3rd edition, Academic Press, Boston, 2009