Assistant Professor @Penn • Dept Psychiatry + Dept Neuroscience 
• Neural circuits • Pain • Opioids • Phil Mind
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1. We’re excited to share our @sciencemagazine paper on the neural basis of painful experiences and discovery of an amygdalar ensemble encoding the unpleasantness of pain, and the potential application of this discovery for blunting the emotional aspects of chronic pain /THREADpic.twitter.com/fopjcKo4Wq
2. First, this was an awesome 5.5 yr collaboration, led by Dr. Biafra Ahanonu (@syscarut) and myself (@FlyBottleEscape), with Drs. Benni Grewe and Dong Wang, and the guidance of Drs. Greg Scherrer and Mark Schnitzer @Stanford and support from @NIDAnews @NINDSnews @HHMINEWS @nyscfpic.twitter.com/x5l8QPW2h2
3. Pain doesn’t feel good but it’s a protective signal that helps heal injuries and avoid future harm. Terribly, millions worldwide suffer from excruciating and inescapable chronic pain, and there is an urgent need to find new, non-addictive alternatives to opioid analgesics
4. Since pain is not merely a sensation but an emotional experience, we went looking for the brain circuits that transform nociception (pain neural information) into an unpleasant and motivating perception. We began with a key emotional brain structure: the basolateral amygdalapic.twitter.com/jvDv6haK7b
5. Combining newly developed assays of affective-motivational pain behavior with miniscope calcium imaging, we identified that ~6% of basolateral amygdala (BLA) neurons encode all types of pain, regardless of sensory mechanisms (heat, cold, mechanical, opto-triggered nociception)pic.twitter.com/jvCeQnmXEt
6. This unconditioned BLA nociceptive ensemble did not encode any other aversive stimuli (footshock, odor, air puff, bitter taste) and was anatomically intermingled but separate from reward encoding neurons, demonstrating a pain-specific circuit-level target for pain reliefpic.twitter.com/y1t2miIKf4
7. Tracking <17,000 BLA neurons during 49d of chronic pain, prior innocuous stimuli engage this nociceptive ensemble, causing benign stimuli such as light touch to become unpleasant and painful. Thereby identifying a neural substrate for the clinical phenomenon of allodynia.pic.twitter.com/5LiMRAxgax
8. Using engineered pain-TRAP mice expressing chemogenetic neuromodulators in the BLA nociceptive ensemble we selectively alleviated the emotional and motivational aspects of chronic pain experiences, without altering pain’s sensory features or rewardpic.twitter.com/qWHznZU86C
9. Can there even be an experience of pain if that perception is devoid of an aversive quality? We urge that targeted treatments to disrupt the BLA nociceptive ensemble, or the broader affective circuits controlling the ensemble, will lead to more effective and safer analgesics.
10. Code use for calcium imaging analysis is available at: https://github.com/bahanonu/calciumImagingAnalysis …
All data relating to this paper are available upon request, because of the size of the data (43 TB)
Learn more at http://www.CorderLab.com @Pennpic.twitter.com/vFxLjI5CB1
11. Thank you to @JasmineDickinso @ktcinlex @CorderNathan and @danieldennett for all your critical and invaluable input on the projectpic.twitter.com/dBK3i0kTnt
And here’s an actual link to the paper 
http://science.sciencemag.org/content/363/6424/276 …
Wow, this is incredible work! Finally got a chance to read it this morning. Why do you think that CNO completely got rid of cold aversion (4F,G) in neuropathic mice, but only got rid of allodynic/hyperalgesic part of response to LT, nox pin, and nox cold (4E)?
Excellent point! The remainder of affective-like behavior in 4E exists largely from the first 2-3 s post stim. We think this is due to intact PB-CeA signaling. Distinction bet CeA v BLA theory address in Supp Note 2
Makes sense, thanks. I also wonder whether your choice to use an allodynic response (light touch) to express noci-TRAP created some selectivity for an allodynic pathway. Would be interesting to see what happens if you express noci-TRAP with noci stim before neuropathic injury
Done that too and it works. From imaging data in the paper we found same exact cells encode acute pain and allodynia Fig 4 and asso supp data. So it doesn’t matter if you TRAP pre or post SNI
Man, you have done it all! This is such excellent work. My hat is off to you and your coauthors.
Very kind of you to say. @syscarut was a beast on this project with me all the way!
Congratulations!! So excited to see where this story goes next!!
Thanks, Nora !!! I’m excited to see where you might take it next 
wow! this is fascinating and so impressive. great summary, too.
Thanks, Dave !! 
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