DT Pain Management Rodent Cancer Models

Pain Management in Rodent Models
of Cancer and Implications for Study

Validity
Presented by
Douglas K. Taylor, DVM, MS, Dipl. ACLAM
September 25, 2020
Continuing Professional Development

Webinar
Agenda
• Pain
– As a stressor and physiological response
• Cancer biology and pain
• Literature review
– Pain effect
– Analgesic effect
The Objective
Established Osteosarcoma
• 100 animals
Model
– Mix of tx and controls
• Intratibial injection
– General anesthesia
– Invasive procedure
– Syngeneic cell line
• Weekly CT imaging
• Lameness ‘scoring’
• Welfare ‘scoring’
• 60 day endpoint or until
non-weight bearing
lameness observed
Defining Pain
• An unpleasant sensory and emotional
experience associated with actual or potential
tissue damage (IASP)
• Many flavors
– Neuropathic, physiologic, pathologic, somatic, visceral
– Acute and chronic
• Two realms
– The Physiological (the sensory)
• Neural pathways
– The Perceived (the emotional)
• Subjective experience e.g. “my pain”
Pain = Physical Stressor
Painful Stimulus
‘Generic’ Responses
• Cardiovascular
– Heart rate, blood pressure
• (Neuro)Endocrine
– Glucocorticoids
– Catecholamines
• Behavioral
• Immunological
Pain & Immune System
The Veterinarian’s Oath
Being admitted to the profession of
veterinary medicine, I solemnly swear to use
my scientific knowledge and skills for the
benefit of society through the protection of
animal health, the relief of animal
suffering, the conservation of animal
resources, the promotion of public health,
and the advancement of medical
knowledge.
Principles IV & V
Unless the contrary is established, investigators
should consider that procedures that cause pain
or distress in human beings may cause pain or
distress in other animals.
Procedures with animals that may cause more

than momentary or slight pain or distress
should be performed with appropriate sedation,
analgesia, or anesthesia.
Cancer Certainly Causes Pain
• 100% in humans with advanced disease
• Almost certainly exists in companion

animals
Why not treat everything?
• Handling stress
• Side effects
– Sedation
– Pica
– Liver or GI impacts
• Pain serves a purpose
• Treatment = a variable
treat treat
• Administer Analgesic Agents • Withhold Analgesic Agents

– Introduce a variable – Potential pain as a variable
Pain, Immunity & Cancer
Human Clinical Data: The Caveats
• Almost all retrospective studies
• Variable
– Patient populations
– Cancer types
– Variable stages of disease
• Cause and effect almost impossible to

determine
– To date: Inconclusive
• 129 Patients
– 50 with
paravertebral and
GA
– 79 with GA only
• Major factors
– Surgery
– Anesthesia
– Opioid analgesia
• 113 Stage IV patients
• Opioid intake estimated
from database
• Poor outcome
– High MOR
expression
– High opioid intake
Compare and Contrast: Human vs
Models
• Humans
– Therapeutic intervention
• Acute, Inflammatory
– Cancerous process
• Chronic, Variable
– Psychological
• Animal Models
– Model induction
• Acute, Inflammatory
– Cancerous process
• Chronic, Variable
• F344 rats
• Laparotomy
• MADB106 cell inoculation
• 2 analgesic regimens
– Intrathecal
bupivacaine and
morphine
– Systemic fentanyl pre
and post sx
• Measure metastasis in
lungs
Opioids and Cancer
• Modulate
– Immune function
– Apoptosis
– Cell adhesion and
invasion
– Angiogenesis
• Nude mice
• MCF-1 breast
cancer cells
• Treatment x 38 d
– Saline
– Morphine
– Naloxone
– Morphine &
Naloxone
NSAIDs and Cancer
• Generally positive
effect
– Control of
inflammation may
play a significant role
– Pro-apoptotic
In vitro
What about ‘psychological’
stress?
• F344 rats
• CRNK-16 cells
given IV
• 80 day timeline
• Several
compounds
administered to
mimic or block
stress response
• Swim stress
So…Here We Are Again
• 100 animals
– Mix of tx and controls
• Intratibial injection
– Invasive procedure
– Syngeneic cell line
• Weekly CT imaging
• Lameness ‘scoring’
• Overall ‘scoring’
• 60 day endpoint or until
non-weight bearing
lameness observed
Conclusions
• We know
– Stressors will impact the model
• Pain
• ‘Psychological’
– Analgesics will impact the model
• Opioids seem variable
• NSAIDs a little more consistent
• We don’t know
– Direct or indirect effect?
– Impact of chronic pain and analgesic administration?
• There is no ground rule to be applied
• Our obligation to maximize animal welfare must be the centering principle
– Thoughtful consideration of every protocol and every model is necessary
– Model translation to human condition
• We need more data
– Chronic administration
– Measuring pain and analgesic efficacy
– Agents typically used for pain control
• Carprofen, Meloxicam, Buprenorphine
Thank You for your time &
attention!
Thank you for the work you

do to promote animal welfare
in biomedical research!
• Swiss Webster mice
• Acute and chronic administration
• Analgesiometry & Immune profile

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DT Pain Management Rodent Cancer Models

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Available Formats

Pain Management in Rodent Models

of Cancer and Implications for Study

Continuing Professional Development

• Cancer biology and pain

Procedures with animals that may cause more

• 100% in humans with advanced disease

• Almost certainly exists in companion

• Administer Analgesic Agents • Withhold Analgesic Agents

• Cause and effect almost impossible to

Thank you for the work you

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