The neuronal circuit that resides in the spinal cord dorsal horn is responsible for accurately relaying and modulating sensory information such as the sensation of pain and itch. In states of persistent itch or pain, this system is imbalanced. To restore the balance in the dorsal horn in a targeted manner, we need to understand how this neuronal circuit is organized, i.e. which neuronal populations that reside there, what their characteristics are and how they can be targeted.
Primary afferent neurons detect changes in the environment through specific ligand-receptor interactions that enable labelled lines for different sensations. For instance, burning and icing pain are sensed by the transient potential receptors V1 and A1, respectively while mechanical pressure is detected by Piezo channels. Histamine receptor 1 expressing neurons on the other hand enables perception of the pruritic substance histamine whereas non-histaminergic itch; initiated for example by the malaria drug chloroquine, the peptide BAM8-22 or alanine, involves activation of MrgprA3, MrgC11 or MrgprD, respectively. While substantial efforts have been made to identify the initiators of pain and itch, little is known about the regulatory mechanisms of primary afferents, especially in itch transmission. We are now focused on identifying how different neurotransmitters regulates itch to identify novel peripheral targets to improve the treatment of persistent itch, which is a dominating symptom in atopic dermatitis and psoriasis.
In the spinal cord, primary afferents terminate on excitatory and inhibitory interneurons that enable regulation and further processing of the incoming signal. We use method development, electrophysiology, pharmacology and advanced transgenic techniques to decipher the regulatory mechanisms of spinal cord interneurons to further understand how sensory networks are regulated in health and disease and to develop novel treatment towards persistent sensory conditions. For further information about ongoing projects, please contact Malin Lagerström.
We are also organizing a 15 ECTS course at bachelor level in Neurobiology provided through the Department of Biology Education at Uppsala University.