Analgesics
Pain is an unpleasant sensory (noxious) and
emotional experience associated with actual or
potential tissue damage
Analgesia –absence, or reduction of pain in
the presence of a stimulus that would normally
be painful
Analgesic – drug that selectively relieves pain by
acting in the CNS or on peripheral pain mechanisms,
Hyperalgesia – an increased sensitivity to a
stimulus that is normally painful
Allodynia – pain caused by a stimulus that is
not 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
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
Types of Pain
Physiological Pain Pathological Pain
• Is a protective Results from tissue injury &
mechanism inflammation
Release of neurotransmitters
• Little to no tissue injury
with ongoing stimulation of
nociceptors
• Pain stops once the
stimulus is removed Can lead to hyperalgesia
Persists after the stimulus is
removed
Types of Pain
Acute Pain Chronic Pain
• Occurs immediately Persists well past the
after a stimulus is initial stimulus (3-6
received months)
• Responds well to May or may not respond
treatment well to treatment; may
require a “multi-modal”
approach
• Subsides once stimulus
is removed Can result in hyperalgesia
Pain Assessment
You 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
Signs of Pain
Lethargy Abnormal posture
Biting/licking at Ruffled coat
injured area Decreased food/water
“Worried” expression consumption
Vocalization Hiding
Disuse of limb “Inwardly” focused
Aggression Disinterest in
Hunched posture environment
Pathophysiology of Pain
Damaged cells release substances which stimulate
nociceptors and inflammation
Noxious stimuli activate nociceptors, resulting in
a lowered stimulation threshold
A-delta nociceptors are myelinated, conduct
impulses rapidly, trigger sensation of first pain
(sharp, pricking pain)
Pathophysiology of Pain
C-fibers are unmyelinated, stimulated by chemicals
released in damaged or inflamed tissues, and
mediates slow, burning pain
Sensitized nociceptors cause the release of glutamate
and neurokinins from the afferent terminals in the
spinal cord
Activates NMDA (N-methyl-D-asparate) receptors,
which are implicated in hypersensitivity (wind-up)
Pathophysiology of Pain
Afferent neurons in the spinal cord relay the signal
to multiple areas in the brain, resulting in the
perception of pain
“Gate control” occurs in the spinal cord, resulting in
early inhibition of nociception, allowing escape
Stimulation of medulary centers result in
hyperventilation, increased cardiac output, and
increased blood pressure
Pathophysiology of Pain
Descending neurons act to modulate pain by
reducing sensation
Various neurotransmitters are released: glutamate,
norepinephrine, serotonin, gamma-aminobutyric
acid (GABA) and endorphins
Analgesia can be induced by blocking the
nociceptive process at one or more points
Four distinct processes involved in nociception
which can be modulated by analgesics:
1. Transduction – translation of the noxious
stimulus into electrical activity at the peripheral
nociceptor
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
2. Transmission – the propagation of nerve
impulses through the nervous system
Can be prevented by local anesthetics applied
along peripheral nerves, at nerve plexus, or in
the epidural or subarachnoid spaces
3. Modulation – modification of nociceptive
transmission by inhibition of the spinal dorsal
horn cells by endorphins
Can be augmented by injection of local
anesthetics or alpha2-adrenergic agonists;
gabapentin may also effect modulation
4. Perception – the final conscious subjective
and emotional experience of pain
Altered by use of general anesthetics or
systemic injection of opioids and/or alpha2-
agonists
Pre-emptive analgesia: giving analgesics prior
to the noxious stimulus (surgery)
Multimodal or “balanced” analgesia: using a
combination of analgesics which will impact
more than one portion of the nociceptive
process
Analgesics
• Divided into five main classes based on
their modes of action
1. Opioids
2. Non-steroidal anti-inflammatory drugs
3. Local anesthetics
4. Alpha2-adrenoceptor agonists
5. Miscellaneous drugs
OPIOIDS
• Narcotic analgesics derived from semi-synthetic
or synthetic sources
• Semi-synthetic:
Hydromorphone, Buprenorphine, Hydrocodone,
Oxycodone, Diacetyl morphine (Heroin)
• Synthetic:
Methadone, Pethidine, Pentazocine, Fentanyl
OPIATES
• Narcotic analgesics derived from opium poppy
plant (natural in origin)
• Morphine, Codeine
Classification of Opioids
Full Agonists
Morphine
Methadone
Pethidine (Meperidine)
Fentanyl
Partial Agonists
Codeine
Hydrocodone
Propoxyphene
Classification of Opioids
Mixed Agonist-Antagonist
• Buprenorphine
• Pentazocine
Antagonists
• Naloxone
• Naltrexone
Endogenous opioid peptides (Endorphins)
• Enkephalins
• Dynorphins
-Endorphins
Opioid Analgesics- Effects
• Analgesia • Respiratory centre
• Euphoria Depression
• Sedation • Contraction of smooth
• muscle, bladder
Emesis
sphincter, pyloric
• Miosis sphincter,
• Antitussive effect • Reduced intestinal
• Release histamine- motility
vasodilator • Reduce uterine tone
Functional effects and opioid receptors
Mu Delta Kappa
Supraspinal analgesia +++ - -
Spinal analgesia ++ ++ ++
Peripheral analgesia ++ - ++
Respiratory depression +++ ++ -
Miosis ++ - +
GI motility ++ ++ +
Euphoria +++ - -
Dysphoria - - +++
Sedation ++ - ++
Dependence +++ - +
Selectivity of Opioid Drugs for receptor
subtypes
Mu Delta Kappa
Morphine, Codeine +++ + +
Methadone ++ - -
Pethidine ++ + +
Pentazocine + + ++
Buprenorphine +++ - ++
Naloxone +++ + ++
Naltrexone +++ + +++
Agonist + Antagonist +
ADVERSE EFFECTS
Euphoria
Sedation
Nausea and Vomiting
Constipation
Urinary Retention
Tolerance and Dependence
Treatment:
• Supportive care
• Naloxone
Why you feel “happy”
• Heroin modifies the action of dopamine in the brain
• Once crossing the blood-brain barrier, heroin is
converted to morphine, which acts as an agonist
• This binding inhibits the release of GABA from the
nerve terminal, reducing the inhibitory effect of
GABA on dopaminergic neurones
Why you feel “happy”
• The increased activation of dopaminergic neurones
and the release of dopamine into the synaptic cleft
results in activation of the post-synaptic membrane.
• Continued activation of the dopaminergic reward
pathway leads to the feelings of euphoria and the
‘high’ associated with heroin use.
Why you feel “happy”
Mechanism of Opioid addiction
• On constant supply of opiate, the brain shows
adaptation, or changes in its circuitry
• When that drug is taken away, neurons that have
been inhibited start pumping out neurotransmitters
again
• This imbalance of chemicals in the brain interacts
with the nervous system to produce the classic
opiate withdrawal symptoms: nausea, muscle
spasms, cramps, anxiety, fever, diarrhea.
Miscellaneous Analgesics
• Tramadol
– Synthetic opioid agonist which also inhibits
serotonin and norepiniphrine re-uptake in the
spinal cord
• Ketamine
– NMDA receptor antagonist
– Basically used as injectable general anesthetic
– More effective treating somatic pain than visceral
pain
• Gabapentin
– Analogue of GABA
– Primarily used as anticonvulsant
– Used to treat nerve pain
