This is the post excerpt.
The Montagna Symposium is held at Salishan with beautiful views of the Pacific Ocean and the picturesque Oregon coast. The setting induces congeniality and stimulating conversations among attendees that occurs after the sessions while enjoying the superb Oregon wines with hors d’oeuvres. This years’ symposium is focused on the skin as a sensory organ with a focus on itch, pain, and pleasure. This is my first year of attending the Montagna Symposium and I plan to attend regularly in the future.
Itch, pain and pleasure sensations are transmitted to the brain via afferent C fibers but there is still much to learn about the parallel pathways. Francis McGlone opened the symposium with a lecture on C tactile (CT) afferents, which transmit the sensation of a pleasurable touch, and describes the skin function as a social organ. He discussed experimental attachment disorders in primates as well as autism disorder as examples of this function gone awry. He also describes alterations in the perception of pleasurable touch. Using a microneurography in which single fibers can be recorded, and with functional MRI, he has shown that these fibers respond best to a gentle caressing touch, which is integral to social interactions in mammals. McGlone introduced the concept of a “hedonic homunculus” and has mapped the CT afferent distribution and interestingly these fibers do not appear in glabrous skin. Experiments in patients with induced spinothalamic tract lesions to ablate pain, show that affective touch was only somewhat attenuated compared to pain and itching which were completely abolished. The hypothesis is that affective touch may be transmitted via a second order pathway
Ethan Lerner chaired the session on itch and opened the session with his provocative hypothesis that the evolutionary purpose of itch is to remove insects as well as keep the immune system active. Are pruritigens antigens or vice versa? It has been demonstrated that removing sensory fibers decreases histologic inflammation in the skin in experimental models of dermatitis. Sarina Elmariah, working in the Lerner’s lab. has demonstrated that neural sprouting precedes inflammation in a mouse model of ovalbumin induced atopic dermatitis. Lerner also described problems in translating mouse experiments to humans and showed data that while neurokinin-1 receptor (NK-1R) antagonism in mice suppresses inflammation and itching, it does not do so in humans in whom Mas-related GPCRs (Mrgprs) mediates itch and inflammation.
As a clinician I am always interested in new ways to address itch. Data was presents showing that loss of GABA control increases itching and inflammation in IL-31 transgenic mouse model. Experiments using GABA receptor agonists baclofen and muscimol inhibited both histamine-dependent and independent itch pathways. Combined low doses of each had a synergistic inhibitory effect on itching in both acute and chronic itching.
The cytokine Thymic Stromal Lymphopoietin (TLSP) is known to be a proinflammatory signal between epithelial cells and the innate immune cells. Diana Bautista presented work that showed that TLSP receptors are also expressed on sensory neurons and injection of TLSP into the skin of mice induced itching and TSLP knock out mice to not itch, demonstrating that TLSP is likely a shared neural and inflammatory signal.
In my next post, I will discuss the puzzle of who itch and pain, which share pathways are experienced so differently and how we respond to each.