Organ Identified Within Dermal-Epidermal Border Adds a New Layer to the Anatomy of Pain

Researchers at the Karolinska Institutet in Stockholm, Sweden, have discovered a previously unknown mesh-like organ covering the skin in mice that senses dangerous environmental stimuli. This organ is built from specialized glial cells located in the epidermal-dermal border and is sufficient and required for initiation of mechanical pain transduction, the authors report in the journal Science.1

After discovering the organ in mice, the team tested its functionality by measuring the rodents' responses to different pain stimuli. When the cells in the organ were turned off via gene editing, all of the mice showed a reduced response to mechanical pain. However, they still showed normal responses to thermal pain.

The newly identified "nociceptive glio-neural complex" is a simple organ made up of a network of glial cells, which are already known to surround and support nerve cells. These glial cells are now reported to form a mesh-like structure between the skin's outer and inner layers, with filament-like protrusions that extend into the skin's outer layer.

"We have been thinking for probably a hundred years that pain is started from nerves in the skin," study coauthor Patrik Ernfors, PhD, Professor of Tissue Biology and a molecular neurobiologist at the Karolinska Institutet in Sweden, told National Geographic. "But what we show now is that pain can also be started in these glial cells."2

The findings change the way scientists think about how pain begins and progresses-at least in mice. The scientists have not yet checked that the organ exists in humans, but Ernfors says the probability is high.

"Considering that all other previously known sensory organs in [mice] also exist in humans, it is possible if not likely that this sensory organ also is present in our skin," Ernfors told the magazine.

Another New Organ Hiding in Plain Sight

In 2018, a study published in the journal Scientific Reports by researchers from the New York University School of Medicine, University of Pennsylvania, Beth Israel Medical Center, and others described a new organ the authors call the "interstitium."3

"The interstitium is a layer of fluid-filled compartments strung together in a web of collagen and a flexible protein called elastin. Previously, scientists thought the layer was simply dense connective tissue," according to an article in National Geographic describing the new study.3

That mesh-like organ exists throughout the human body, surrounding blood vessels, encasing the tissue between muscles, and lining the digestive, respiratory, and urinary systems.

Like the glial network, the interstitium had seemingly been hidden in plain sight. Scientists may have missed it because of the way tissue is studied-samples are thinly sliced and treated with chemicals to identify key components more easily. But that process drains fluid from the sample.

Devoid of their fluid, the compartments of the interstitium collapse, leaving the whole structure to flatten. To find these pockets of interstitial fluid, medical researchers looked at living tissue instead of sampling dead tissue samples, using a probing technique called confocal laser endomicroscopy.3

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