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High Speed Imaging of Pain in Mice

published by Nathan Fried

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Pain: Largest U.S. Public Health Crisis

(millions)100100292930301616PainHeart DiseaseDiabetesCancerPatientPopulation0255075100

Lost Productivity

$261 - $300 billion

$299 - $334 billion

Health Care

Heart Disease ($309 billion)

Diabetes ($188 billion)

Cancer ($243 billion)

greater
than

560

635b

$

-  $

Annual costs
associated for 
chronic pain patients

100

million pain
patients

Opioid Epidemic Partly Driven by Lack of Treatments for Chronic Pain

91 

americans

die every day from
an opioid overdose (including prescription opioids & heroin)

Half

nearly

of all opioid overdose deaths involve a prescription 
opioid

Finding safer treatments starts with basic science. But how do we assess pain to know if a treatment works?

In humans,
you ask.

In mice,
you do behavior.

Three Behavior Assay Types

A Human Pain Scale

1. Reflex-based assays with paw or tail

2. Operant-based assays

3. Spontaneous pain behaviors (i.e., eye grimace, back-arch, paw shake/lick, paw guard,  vocalization, abnormal grooming, etc.)

Most preclinical studies use these reflex-based assays. BUT, just because a mouse responds to your stimuli at an increased frequency doesn't necessarily mean it's in pain!

1189

Only 11% of pain therapeutics entering Phase 1 become approved by the FDA.

The Problem?

The Solution?

The current reflex-based assays to assess pain in mice may be unreliable and seem to lack predictive validity. 

Utilize high speed-imaging, statistical modeling, machine learning, and modern neuroscience behavioral approaches to refine our interpretation of reflex-based assays.

Naked Eye

High Speed
Camera

Identification of Behavioral syl·la·bles

Statistical Modeling
and Machine Learning

Creation of Mouse Pain Scale

-2-114blank-2024

Assumptions of why the rodent moved

Incorrect assessment of pain

Objective Assessment of Pain

No Pain

Some Pain

No Pain

Lots of Pain

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5

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1) Gaskin, D.J., and Richard, P. (2012). The Economic Costs of Pain in the United States. The Journal of Pain 13, 715–724. 2) Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011. 3) Rudd, R.A. (2016). Increases in Drug and Opioid-Involved Overdose Deaths — United States, 2010–2015. MMWR Morb Mortal Wkly Rep 65. 4) Allie Boyfriend Doesn’t Have Ebola. Probably, image from blog post:  5) Barrot, M. (2012). Tests and models of nociception and pain in rodents. Neuroscience 211, 39-50. 6) Hay, M., Thomas, D.W., Craighead, J.L., Economides, C., and Rosenthal, J. (2014). Clinical development success rates for investigational drugs. Nat Biotechnol 32, 40-51.

Citations

PC/Pain Score