⚡️GREG_CORDER⚡️

Research Highlight: Targeting the affective dimension of pain www.nature.com/articles/s41...

Good

The Stanford Encyclopedia of Philosophy just published a revised entry on Animal Consciousness! By Michael Trestman, Jonathan Birch, Colin Allen @wileyprof.bsky.social @birchlse.bsky.social plato.stanford.edu/entries/cons...

A consensus spinal cord cell type atlas across mouse, macaque, and human https://www.biorxiv.org/content/10.64898/2026.02.04.703852v1

!!!!! TENURE !!!!!

i am always shocked at the number of papers without verification of fiber placement or check if their AAV expressed etc ... and when i am a reviewer and ask for it then sometimes i have gotten wildly "offended" resposnes from authors

actually, someone in lab sent me this: AAVretro inject into ~ Cg2 ... those look like labeled anterior insula in this iamge ... but we do not see posterior insula

After a gentle touch to a mouse’s injured paw, a brain region involved in the emotional side of pain lights up, as seen in this mouse brain cross-section. The blue and pink signals mark genes that switch on when neurons become active. This allowed the researchers to map a pain-responsive hotspot and then target a specific opioid-related circuit. Image credit: Gregory Corder, Corinna Oswell, and Nora McCall

By splitting #pain into its component parts, researchers provide pain relief in #mice. In PNAS Journal Club: https://ow.ly/eHT750Y1eGh

#ChronicPain #opioid #MachineLearning #AnteriorCingulateCortex

!!! Same… also the histology in this part’s gig 1 just looks like bleed thru?

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

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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...

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

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

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

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

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

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

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

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

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

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

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)

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

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