published by Nathan Fried
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Pain: Largest U.S. Public Health Crisis
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!
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
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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2
3
4
5
6
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