⚡️GREG_CORDER⚡️
@flybottleescape.bsky.social
Assistant Professor @ Penn | Dept Psychiatry + Dept Neuroscience + Dept Anesthesiology | Pain • Placebo • Poppies • Psychedelics
https://corderlab.com/
https://corderlab.com/
Pinned
Researchers identify the neurons involved in the emotional distress associated with pain
go.nature.com/4qIKkB8
go.nature.com/4qIKkB8
Chronic pain could be eased by uncoupling the sensory and emotional experiences
Researchers identify the neurons involved in the emotional distress associated with pain, and design a genetic approach that could soothe suffering without opioid drugs.
go.nature.com
🧠⚡️💊New @nature.com publication !
Mimicking opioid analgesia in cortical pain circuits
We built a brain-behavior framework to decode spontaneous chronic pain in mice—and to biologically mimic morphine with a synthetic opioid gene therapy
nature.com/articles/s41...
@pennmedicine.bsky.social
Mimicking opioid analgesia in cortical pain circuits
We built a brain-behavior framework to decode spontaneous chronic pain in mice—and to biologically mimic morphine with a synthetic opioid gene therapy
nature.com/articles/s41...
@pennmedicine.bsky.social
thank you! we didnt try the combo therapy+morphine .... could be intersting to look at something like cross-tolerance, or is there something else you think we should try out
January 15, 2026 at 7:33 PM
thank you! we didnt try the combo therapy+morphine .... could be intersting to look at something like cross-tolerance, or is there something else you think we should try out
Please check out the Peer Review file to see how our publication process unfolded
... as well as the Supplementary Information file for expanded Discussion Notes 1-7
👇
nature.com/articles/s41...
... as well as the Supplementary Information file for expanded Discussion Notes 1-7
👇
nature.com/articles/s41...
January 8, 2026 at 6:18 PM
Please check out the Peer Review file to see how our publication process unfolded
... as well as the Supplementary Information file for expanded Discussion Notes 1-7
👇
nature.com/articles/s41...
... as well as the Supplementary Information file for expanded Discussion Notes 1-7
👇
nature.com/articles/s41...
Brought to you by the 6+ years of dedication from these amazing scientists ...
Huge congrats to the co-First authors:
Corinna Oswell, Sophie Rogers, Justin James
... and co-Senior authors:
Eric Yttri, Karl Deisseroth, Ben Reiner
Huge congrats to the co-First authors:
Corinna Oswell, Sophie Rogers, Justin James
... and co-Senior authors:
Eric Yttri, Karl Deisseroth, Ben Reiner
January 8, 2026 at 6:10 PM
Brought to you by the 6+ years of dedication from these amazing scientists ...
Huge congrats to the co-First authors:
Corinna Oswell, Sophie Rogers, Justin James
... and co-Senior authors:
Eric Yttri, Karl Deisseroth, Ben Reiner
Huge congrats to the co-First authors:
Corinna Oswell, Sophie Rogers, Justin James
... and co-Senior authors:
Eric Yttri, Karl Deisseroth, Ben Reiner
15/ 🚀 LUPE + AMPS + ACC pLick neurons + mMORp = blueprint for decoding and treating affective pain
Spontaneous behavior is the readout
Cortex is the control panel
And we just built a new switch
nature.com/articles/s41...
#Neuroscience #Pain #DeepLearning #GeneTherapy
Spontaneous behavior is the readout
Cortex is the control panel
And we just built a new switch
nature.com/articles/s41...
#Neuroscience #Pain #DeepLearning #GeneTherapy
January 8, 2026 at 6:08 PM
15/ 🚀 LUPE + AMPS + ACC pLick neurons + mMORp = blueprint for decoding and treating affective pain
Spontaneous behavior is the readout
Cortex is the control panel
And we just built a new switch
nature.com/articles/s41...
#Neuroscience #Pain #DeepLearning #GeneTherapy
Spontaneous behavior is the readout
Cortex is the control panel
And we just built a new switch
nature.com/articles/s41...
#Neuroscience #Pain #DeepLearning #GeneTherapy
14/ 💥 Key insight: Spontaneous pain isn’t random—it’s structured, stateful, and encoded in affective brain circuits
The ACC selects actions to reduce pain unpleasantness
And now, we can decode those states, track their dynamics, and intervene in real time
The ACC selects actions to reduce pain unpleasantness
And now, we can decode those states, track their dynamics, and intervene in real time
January 8, 2026 at 6:07 PM
14/ 💥 Key insight: Spontaneous pain isn’t random—it’s structured, stateful, and encoded in affective brain circuits
The ACC selects actions to reduce pain unpleasantness
And now, we can decode those states, track their dynamics, and intervene in real time
The ACC selects actions to reduce pain unpleasantness
And now, we can decode those states, track their dynamics, and intervene in real time
13/ 🧠📷 Activating this therapy silenced pain-related ACC activity and reduced LUPE-AMPS pain behaviors—just like morphine
But there was no reinforcment (less risk of addiction)
A new, non-opioid way to control cortical pain dynamics
But there was no reinforcment (less risk of addiction)
A new, non-opioid way to control cortical pain dynamics
January 8, 2026 at 6:06 PM
13/ 🧠📷 Activating this therapy silenced pain-related ACC activity and reduced LUPE-AMPS pain behaviors—just like morphine
But there was no reinforcment (less risk of addiction)
A new, non-opioid way to control cortical pain dynamics
But there was no reinforcment (less risk of addiction)
A new, non-opioid way to control cortical pain dynamics
12/ 🧬 Could we mimic morphine’s effects—but without opioids?
We engineered a synthetic MOR promoter (mMORp) that drives chemogenetic inhibition only in opioid-sensitive, pain-encoding ACC neurons
A targeted, biologically informed strategy for precision pain managment
We engineered a synthetic MOR promoter (mMORp) that drives chemogenetic inhibition only in opioid-sensitive, pain-encoding ACC neurons
A targeted, biologically informed strategy for precision pain managment
January 8, 2026 at 6:06 PM
12/ 🧬 Could we mimic morphine’s effects—but without opioids?
We engineered a synthetic MOR promoter (mMORp) that drives chemogenetic inhibition only in opioid-sensitive, pain-encoding ACC neurons
A targeted, biologically informed strategy for precision pain managment
We engineered a synthetic MOR promoter (mMORp) that drives chemogenetic inhibition only in opioid-sensitive, pain-encoding ACC neurons
A targeted, biologically informed strategy for precision pain managment
11/ ⏱️ In chronic pain, yes, mice show spontaneous licking behavior (no need to do CPP) pLick neurons became less selective and less responsive
Morphine rescued this—restoring lick-locked activity and state decoding
The better the neural rescue, the lower the pain scores
Morphine rescued this—restoring lick-locked activity and state decoding
The better the neural rescue, the lower the pain scores
January 8, 2026 at 6:06 PM
11/ ⏱️ In chronic pain, yes, mice show spontaneous licking behavior (no need to do CPP) pLick neurons became less selective and less responsive
Morphine rescued this—restoring lick-locked activity and state decoding
The better the neural rescue, the lower the pain scores
Morphine rescued this—restoring lick-locked activity and state decoding
The better the neural rescue, the lower the pain scores
10/ 📉 Morphine didn’t just reduce behavior—it silenced specific ACC neurons active during pain states
We discovered “pLick neurons” whose activity predicts licking probability
Morphine suppressed pLick neurons in a state- and behavior-dependent manner
We discovered “pLick neurons” whose activity predicts licking probability
Morphine suppressed pLick neurons in a state- and behavior-dependent manner
January 8, 2026 at 6:05 PM
10/ 📉 Morphine didn’t just reduce behavior—it silenced specific ACC neurons active during pain states
We discovered “pLick neurons” whose activity predicts licking probability
Morphine suppressed pLick neurons in a state- and behavior-dependent manner
We discovered “pLick neurons” whose activity predicts licking probability
Morphine suppressed pLick neurons in a state- and behavior-dependent manner
9/ 🧠 LUPE-AMPS tracking + neural data revealed that ACC activity predicts transitions between latent pain states
We could decode spontaneous behaviors like licking directly from ACC population activity
Spontaneous neural activity is not noise—it encodes affective decisions
We could decode spontaneous behaviors like licking directly from ACC population activity
Spontaneous neural activity is not noise—it encodes affective decisions
January 8, 2026 at 6:05 PM
9/ 🧠 LUPE-AMPS tracking + neural data revealed that ACC activity predicts transitions between latent pain states
We could decode spontaneous behaviors like licking directly from ACC population activity
Spontaneous neural activity is not noise—it encodes affective decisions
We could decode spontaneous behaviors like licking directly from ACC population activity
Spontaneous neural activity is not noise—it encodes affective decisions
8/ 🏛️ Enter the ACC: a cortical hub for affective pain
We did in vivo calcium imaging with miniscopes in freely behaving mice across acute capsaicin injury and SNI chronic neuropathic injury
This let us track how ACC neural ensembles reorganize as pain becomes chronic
We did in vivo calcium imaging with miniscopes in freely behaving mice across acute capsaicin injury and SNI chronic neuropathic injury
This let us track how ACC neural ensembles reorganize as pain becomes chronic
January 8, 2026 at 6:04 PM
8/ 🏛️ Enter the ACC: a cortical hub for affective pain
We did in vivo calcium imaging with miniscopes in freely behaving mice across acute capsaicin injury and SNI chronic neuropathic injury
This let us track how ACC neural ensembles reorganize as pain becomes chronic
We did in vivo calcium imaging with miniscopes in freely behaving mice across acute capsaicin injury and SNI chronic neuropathic injury
This let us track how ACC neural ensembles reorganize as pain becomes chronic
7/ 👅Licking is an affective-motivational behavior emerging during Pain States
This structure supports the original Gate Control Theory that rubbing/licking is an antinociceptive negative feedback loop to reduce pain
Pain drives licking → licking reduces pain → licking stops
This structure supports the original Gate Control Theory that rubbing/licking is an antinociceptive negative feedback loop to reduce pain
Pain drives licking → licking reduces pain → licking stops
January 8, 2026 at 6:04 PM
7/ 👅Licking is an affective-motivational behavior emerging during Pain States
This structure supports the original Gate Control Theory that rubbing/licking is an antinociceptive negative feedback loop to reduce pain
Pain drives licking → licking reduces pain → licking stops
This structure supports the original Gate Control Theory that rubbing/licking is an antinociceptive negative feedback loop to reduce pain
Pain drives licking → licking reduces pain → licking stops
6/ 📈 To quantify this, we built a new metric: the Affective-Motivational Pain Scale (AMPS)
AMPS captures the bidirectional effects of both injury and analgesia
A single, continuous index of spontaneous pain state occupancy across models (formalin, capsaicin, SNI)
AMPS captures the bidirectional effects of both injury and analgesia
A single, continuous index of spontaneous pain state occupancy across models (formalin, capsaicin, SNI)
January 8, 2026 at 6:03 PM
6/ 📈 To quantify this, we built a new metric: the Affective-Motivational Pain Scale (AMPS)
AMPS captures the bidirectional effects of both injury and analgesia
A single, continuous index of spontaneous pain state occupancy across models (formalin, capsaicin, SNI)
AMPS captures the bidirectional effects of both injury and analgesia
A single, continuous index of spontaneous pain state occupancy across models (formalin, capsaicin, SNI)
5/ 🔍 Using Markov modeling + unsupervised clustering, we identified 6 reproducible latent states in pain models
Some states (like Pain State-4) were selectively increased by injury and suppressed by morphine
Pain is not binary—it’s multivalent, dynamic, and opioid-sensitive
Some states (like Pain State-4) were selectively increased by injury and suppressed by morphine
Pain is not binary—it’s multivalent, dynamic, and opioid-sensitive
January 8, 2026 at 6:03 PM
5/ 🔍 Using Markov modeling + unsupervised clustering, we identified 6 reproducible latent states in pain models
Some states (like Pain State-4) were selectively increased by injury and suppressed by morphine
Pain is not binary—it’s multivalent, dynamic, and opioid-sensitive
Some states (like Pain State-4) were selectively increased by injury and suppressed by morphine
Pain is not binary—it’s multivalent, dynamic, and opioid-sensitive
4/ 📊 LUPE revealed a constellation of pain-related behaviors—especially recuperative paw licking
We used these to define latent behavioral states that evolve over seconds to minutes
Each state reflects a distinct pain “mode”—not a single action, but a strategy
We used these to define latent behavioral states that evolve over seconds to minutes
Each state reflects a distinct pain “mode”—not a single action, but a strategy
January 8, 2026 at 6:02 PM
4/ 📊 LUPE revealed a constellation of pain-related behaviors—especially recuperative paw licking
We used these to define latent behavioral states that evolve over seconds to minutes
Each state reflects a distinct pain “mode”—not a single action, but a strategy
We used these to define latent behavioral states that evolve over seconds to minutes
Each state reflects a distinct pain “mode”—not a single action, but a strategy
3/ 🐭 We built LUPE: a deep-learning system that tracks spontaneous, naturalistic behaviors in mice at high resolution
No pokes, no prods—just the animal alone with its pain
This allows us to ask: how does pain actually change what an animal does?
No pokes, no prods—just the animal alone with its pain
This allows us to ask: how does pain actually change what an animal does?
January 8, 2026 at 6:02 PM
3/ 🐭 We built LUPE: a deep-learning system that tracks spontaneous, naturalistic behaviors in mice at high resolution
No pokes, no prods—just the animal alone with its pain
This allows us to ask: how does pain actually change what an animal does?
No pokes, no prods—just the animal alone with its pain
This allows us to ask: how does pain actually change what an animal does?
2/ 🧠 Chronic pain is more than a sensory perception—it’s an affective state that disrupts behavior, motivation, and mood
But internal states like pain are hard to observe directly
We tackled this by decoding spontaneous behavior + brain activity in mice
But internal states like pain are hard to observe directly
We tackled this by decoding spontaneous behavior + brain activity in mice
January 8, 2026 at 6:01 PM
2/ 🧠 Chronic pain is more than a sensory perception—it’s an affective state that disrupts behavior, motivation, and mood
But internal states like pain are hard to observe directly
We tackled this by decoding spontaneous behavior + brain activity in mice
But internal states like pain are hard to observe directly
We tackled this by decoding spontaneous behavior + brain activity in mice
🧠⚡️💊New @nature.com publication !
Mimicking opioid analgesia in cortical pain circuits
We built a brain-behavior framework to decode spontaneous chronic pain in mice—and to biologically mimic morphine with a synthetic opioid gene therapy
nature.com/articles/s41...
@pennmedicine.bsky.social
Mimicking opioid analgesia in cortical pain circuits
We built a brain-behavior framework to decode spontaneous chronic pain in mice—and to biologically mimic morphine with a synthetic opioid gene therapy
nature.com/articles/s41...
@pennmedicine.bsky.social
Researchers identify the neurons involved in the emotional distress associated with pain
go.nature.com/4qIKkB8
go.nature.com/4qIKkB8
Chronic pain could be eased by uncoupling the sensory and emotional experiences
Researchers identify the neurons involved in the emotional distress associated with pain, and design a genetic approach that could soothe suffering without opioid drugs.
go.nature.com
January 8, 2026 at 6:01 PM
🧠⚡️💊New @nature.com publication !
Mimicking opioid analgesia in cortical pain circuits
We built a brain-behavior framework to decode spontaneous chronic pain in mice—and to biologically mimic morphine with a synthetic opioid gene therapy
nature.com/articles/s41...
@pennmedicine.bsky.social
Mimicking opioid analgesia in cortical pain circuits
We built a brain-behavior framework to decode spontaneous chronic pain in mice—and to biologically mimic morphine with a synthetic opioid gene therapy
nature.com/articles/s41...
@pennmedicine.bsky.social
Reposted by ⚡️GREG_CORDER⚡️
Researchers identify the neurons involved in the emotional distress associated with pain
go.nature.com/4qIKkB8
go.nature.com/4qIKkB8
Chronic pain could be eased by uncoupling the sensory and emotional experiences
Researchers identify the neurons involved in the emotional distress associated with pain, and design a genetic approach that could soothe suffering without opioid drugs.
go.nature.com
January 8, 2026 at 9:12 AM
Researchers identify the neurons involved in the emotional distress associated with pain
go.nature.com/4qIKkB8
go.nature.com/4qIKkB8