Tag: 17/3/25

Categories : Neurology Pain ManagementTags : Leave a comment

Innovative In Vivo Imaging Offers New Treatment and Hope for Chronic TMJ Pain

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Photo by engin akyurt on Unsplash

Facial pain and discomfort related to the temporomandibular joint (TMJ) is the second-leading musculoskeletal disorder, after chronic back pain, affecting 8% to 12% of Americans. Current treatments for TMJ disorders are not always sufficient, leading researchers to further explore the vast nerve and vessel network connected to this joint – the second largest in the human body.

In a study published in December 2024 in the journal Pain, a research team led by Yu Shin Kim, PhD, associate professor at the The University of Health Science Center at San Antonio (UT Health San Antonio), observed for the first time the simultaneous activity of more than 3000 trigeminal ganglion (TG) neurons, which are cells clustered at the base of the brain that transmit information about sensations to the face, mouth and head.

“With our novel imaging technique and tools, we can see each individual neuron’s activity, pattern and dynamics as well as 3000 neuronal populational ensemble, network pattern and activities in real time while we are giving different stimuli,” said Kim.

When the TMJ is injured or misaligned, it sends out signals to increase inflammation to protect the joint. However, this signaling can lead to long-term inflammation of the joint and other parts of the highly connected nerve network, leading to chronic pain and discomfort. About 80% to 90% of TMJ disorders occur in women, and most cases develop between the ages of 15–50.

Activation at the cellular level

Previous animal studies observed behavioural changes related to pain, but this study was the first to record reactions at the cellular level and their activities. To see which portions of the nerve pathway respond to various types of pain, Kim’s team created different models of pain and observed the neuronal activity with high-resolution confocal imaging, which uses a high-resolution camera and scanning system to observe neurons in action.

The team discovered that during TMJ activation, more than 100 neurons spontaneously fire at the same time. Activation was observed in localised areas of the TMJ innervated to TG neurons. The localisation of this activation highlights the specific neural pathways involved in TMJ pain, offering deeper insight into how pain develops and spreads to nearby areas. The study is also the first to quantify the degree of TG neuronal sensitivity and network activities.

Potential link to migraine, headaches

Chronic TMJ pain in humans is often linked to other pain comorbidity such as migraines and other headaches. Kim’s team observed this crossover in the in vivo model as inflammation of TG neurons spread to the nearby orofacial areas. Kim’s previous research demonstrated how stress-related migraine pain originates from a certain molecule, begins in the dura and innervates throughout the dura and TG neurons. This current study and novel imaging technique further reveals potential connections between the TMJ, migraines and other headaches.

Potential of CGRP treatment

Calcitonin gene-related peptides (CGRP), molecules involved in transmitting pain signals and regulating inflammation, are often found in higher amounts in synovial fluid of TMJ disorder patients. Synovial fluid surrounds joints in the body, helping to reduce friction between bones and cartilage. Higher amounts of CGRP are often associated with increased pain and inflammation. Kim hypothesised in this study that a reduction in CGRP may reduce TMJ disorder symptoms. He found that CGRP antagonist added to the synovial fluid relieved both TMJ pain and hypersensitivity of TG neurons.

Currently, there are no Federal Drug Administration-approved medications for TMJ disorders other than non-steroidal anti-inflammatory drugs (NSAIDS). While some CGRP antagonist medications are FDA-approved for treating migraines, this study suggests these drugs may also provide relief for TMJ disorders. Confirmation of the positive effect of the drug on TMJ pain is a major leap forward in understanding how CGRP affect TMJ pain, said Kim.

“This imaging technique and tool allows us to see pain at its source – down to the activity of individual neurons – offering unprecedented insights into how pain develops and spreads. Our hope is that this approach will not only advance treatments for TMJ disorders but also pave the way for understanding and managing various chronic pain conditions more effectively,” said Kim.

Source: University of Texas Health Science Center at San Antonio

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Dopamine has an Unexpected Role in Memory Devaluation

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Photo by Fakurian Design on Unsplash

New research out of Michigan State University expands on current understanding of the brain chemical dopamine, finding that it plays a role in reducing the value of memories associated with rewards. The study, published in Communications Biology, opens new avenues for understanding dopamine’s role in the brain.

The research team discovered that dopamine is involved in reshaping memories of past rewarding events – an unexpected function that challenges established theories of dopamine function.

“We discovered that dopamine plays a role in modifying how a reward-related memory is perceived over time,” said Alexander Johnson, associate professor in MSU’s Department of Psychology and lead researcher of the study.

In the study, mice were presented with an auditory cue that had previously been associated with a sweet-tasting food. This led to a retrieval of the memory associated with consuming the food. At this time, mice were made to feel temporarily unwell, similar to how you feel if you’ve eaten something that has upset your stomach.

When the mice had fully recovered, they displayed behaviour as if the sweet-tasting food had made them unwell. This occurred despite the fact that when mice were made to feel unwell, they had only retrieved the memory of the food, not the food itself. This initial finding suggests that devaluing the memory of food is sufficient to disrupt future eating of that food.

The research team next turned their attention to the brain mechanisms that could be controlling this phenomenon. Using an approach by which they could label and reactivate brain cells that were engaged when the food memory was retrieved, the researchers identified that cells producing the chemical dopamine appeared to play a particularly important role. This was confirmed through actions that manipulated and recorded dopamine neuron activity during the exercise.

“Our findings were surprising based on our prior understanding of dopamine’s function. We typically don’t tend to think of dopamine being involved in the level of detailed informational and memory processing that our study showed,” Johnson explained. “It’s a violation of what we expected, revealing that dopamine’s role is more complex than previously thought.”

The team also used computational modelling and were able to capture how dopamine signals would go about playing this role in reshaping reward memories.

“Understanding dopamine’s broader functions in the brain could provide new insights into how we approach conditions like addiction, depression and other neuropsychiatric disorders,” said Johnson. “Since dopamine is implicated in so many aspects of brain function, these insights have wide-ranging implications. In the future, we may be able to use these approaches to reduce the value of problematic memories and, as such, diminish their capacity to control unwanted behaviours.”

Source: Michigan State University