Joshua Emrick
@jjemrick.bsky.social
Sensory biologist and dentist.
Pulp fact: The tooth sensory system functions to help protect these critical, irreplaceable organs. We have additional reason to keep our dental pulp (and nerves) healthy.
August 6, 2025 at 4:57 PM
Pulp fact: The tooth sensory system functions to help protect these critical, irreplaceable organs. We have additional reason to keep our dental pulp (and nerves) healthy.
Above all, we see the good in the intradental neurons. In fact, it seems that their conservation across mammals makes more sense. Tooth damage represents a fairly cataclysmic consequence for an animal in the wild (without options for dental care).
August 6, 2025 at 4:57 PM
Above all, we see the good in the intradental neurons. In fact, it seems that their conservation across mammals makes more sense. Tooth damage represents a fairly cataclysmic consequence for an animal in the wild (without options for dental care).
Key experiments with our collaborator (Peng and Karin) helped control for non-specific activation of sensory neurons and helped to confirm that even activation of the intradental neuron cell bodies (that were captured with AAV transduction) produced EMG activity in the muscle that opens the jaw.
August 6, 2025 at 4:57 PM
Key experiments with our collaborator (Peng and Karin) helped control for non-specific activation of sensory neurons and helped to confirm that even activation of the intradental neuron cell bodies (that were captured with AAV transduction) produced EMG activity in the muscle that opens the jaw.
There were many reasons why we may have failed to identify the reflex response. The anesthesia could have been too deep. The light wouldn't penetrate deeply enough. The response would only inhibit muscle contraction, not activate contraction.
August 6, 2025 at 4:57 PM
There were many reasons why we may have failed to identify the reflex response. The anesthesia could have been too deep. The light wouldn't penetrate deeply enough. The response would only inhibit muscle contraction, not activate contraction.
We put the mouse under light isoflurane and found that its jaw made the slightest opening, very briefly, when we activated the terminals in the tooth! I was in the room where it happened (holding the fiber).
August 6, 2025 at 4:57 PM
We put the mouse under light isoflurane and found that its jaw made the slightest opening, very briefly, when we activated the terminals in the tooth! I was in the room where it happened (holding the fiber).
So, if the intradental neurons fire immediately and transiently during superficial damage, what happens when they are transiently activated? This was a critical experiment for this project. We wanted to try to see what would happen if we activation of the intradental neurons using optogenetics.
August 6, 2025 at 4:57 PM
So, if the intradental neurons fire immediately and transiently during superficial damage, what happens when they are transiently activated? This was a critical experiment for this project. We wanted to try to see what would happen if we activation of the intradental neurons using optogenetics.
We are now considering how to use this model to explore what tooth pain further. It's now a 2nd tool (in addition to TG calcium imaging) for us to use to evaluate dental pain and analgesics.
August 6, 2025 at 4:57 PM
We are now considering how to use this model to explore what tooth pain further. It's now a 2nd tool (in addition to TG calcium imaging) for us to use to evaluate dental pain and analgesics.
Activation of the intradental neurons using chemogenetics gave us predictable, but key result... we found distinct behavior with features that indicated pain (corroborating previous reports). It was also stunning that the pain was on par with systemic, broad activation of nociceptors.
August 6, 2025 at 4:57 PM
Activation of the intradental neurons using chemogenetics gave us predictable, but key result... we found distinct behavior with features that indicated pain (corroborating previous reports). It was also stunning that the pain was on par with systemic, broad activation of nociceptors.
We were excited to test a genetic approach to delete Scn10a (which encodes the alpha-subunit of Nav1.8) because of new analgesics... did not prevent intradental responses... it seems as if newly-developed antagonists for Nav1.8 are unlikely to prevent any pain from intradental activation.
August 6, 2025 at 4:57 PM
We were excited to test a genetic approach to delete Scn10a (which encodes the alpha-subunit of Nav1.8) because of new analgesics... did not prevent intradental responses... it seems as if newly-developed antagonists for Nav1.8 are unlikely to prevent any pain from intradental activation.
There are some assumptions we are making in interpreting our results, but these data might hint that the molecular mechanoreceptor in question remains at-large (and represents a major unknown more broadly)...
August 6, 2025 at 4:57 PM
There are some assumptions we are making in interpreting our results, but these data might hint that the molecular mechanoreceptor in question remains at-large (and represents a major unknown more broadly)...
Many reports suggested that Piezo2 might be the major molecular mediator for dental sensation. Alas, as much as we would have loved to find the mechanoreceptor, when we knocked out Piezo2 from the intradental neurons, we still found their responses.
August 6, 2025 at 4:57 PM
Many reports suggested that Piezo2 might be the major molecular mediator for dental sensation. Alas, as much as we would have loved to find the mechanoreceptor, when we knocked out Piezo2 from the intradental neurons, we still found their responses.
We also linked our work to past reports because we found that our neurons of interest also responded once the dentin had been exposed. We also used genetic and viral labeling to confirm that the HTMRs provided dentin innervation (& define their terminal morphology and receptive fields).
August 6, 2025 at 4:57 PM
We also linked our work to past reports because we found that our neurons of interest also responded once the dentin had been exposed. We also used genetic and viral labeling to confirm that the HTMRs provided dentin innervation (& define their terminal morphology and receptive fields).
Our work links intradental neurons to our latest understanding of somatosensory neurons. Our prior report predicted these neurons would be specialized high-threshold mechanoreceptors (HTMRs) based on their transcriptional expression, but these new experiments confirmed this function.
August 6, 2025 at 4:57 PM
Our work links intradental neurons to our latest understanding of somatosensory neurons. Our prior report predicted these neurons would be specialized high-threshold mechanoreceptors (HTMRs) based on their transcriptional expression, but these new experiments confirmed this function.
We were surprised to find that a majority responded to even slight surface damage. More responded as the damage increased.
August 6, 2025 at 4:57 PM
We were surprised to find that a majority responded to even slight surface damage. More responded as the damage increased.
We used calcium imaging with electrical stimulation of the tooth to find the intradental neurons without physically damaging the tooth structure. This approach was technically-challenging (mouse mouth and teeth = small), but opened the door to understanding what exactly causes them to fire.
August 6, 2025 at 4:57 PM
We used calcium imaging with electrical stimulation of the tooth to find the intradental neurons without physically damaging the tooth structure. This approach was technically-challenging (mouse mouth and teeth = small), but opened the door to understanding what exactly causes them to fire.
These findings corresponded well to what we observed in the dental clinic - dentin stimulation triggered pain. The trouble was that most of these experiments had to shave off the enamel to stimulate the dentin - so almost none of these data were collected with the tooth intact.
August 6, 2025 at 4:57 PM
These findings corresponded well to what we observed in the dental clinic - dentin stimulation triggered pain. The trouble was that most of these experiments had to shave off the enamel to stimulate the dentin - so almost none of these data were collected with the tooth intact.
We were well aware that the tooth innervation was capable of causing pain. Previously, careful ephys experiments demonstrated that many other mammals had sensory innervation within the tooth that fired to mechanical stimulation.
August 6, 2025 at 4:57 PM
We were well aware that the tooth innervation was capable of causing pain. Previously, careful ephys experiments demonstrated that many other mammals had sensory innervation within the tooth that fired to mechanical stimulation.
TL;DR
Pulp fact: The tooth sensory system functions to help protect these critical, irreplaceable organs. We have additional reason to keep our dental pulp (and nerves) healthy.
See below for the deep cuts.
Pulp fact: The tooth sensory system functions to help protect these critical, irreplaceable organs. We have additional reason to keep our dental pulp (and nerves) healthy.
See below for the deep cuts.
August 6, 2025 at 4:57 PM
TL;DR
Pulp fact: The tooth sensory system functions to help protect these critical, irreplaceable organs. We have additional reason to keep our dental pulp (and nerves) healthy.
See below for the deep cuts.
Pulp fact: The tooth sensory system functions to help protect these critical, irreplaceable organs. We have additional reason to keep our dental pulp (and nerves) healthy.
See below for the deep cuts.
Please add me! Thanks!
July 30, 2025 at 7:33 PM
Please add me! Thanks!