Runx1 Determines Nociceptive Sensory Neuron Phenotype and Is Required for Thermal and Neuropathic Pain

Abstract

In mammals, the perception of pain is initiated by the transduction of noxious stimuli through specialized ion channels and receptors expressed by nociceptive sensory neurons. The molecular mechanisms responsible for the specification of distinct sensory modality are, however, largely unknown. We show here that Runx1, a Runt domain transcription factor, is expressed in most nociceptors during embryonic development but in adult mice, becomes restricted to nociceptors marked by expression of the neurotrophin receptor Ret. In these neurons, Runx1 regulates the expression of many ion channels and receptors, including TRP class thermal receptors, Na+-gated, ATP-gated, and H+-gated channels, the opioid receptor MOR, and Mrgpr class G protein coupled receptors. Runx1 also controls the lamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. Thus, Runx1 coordinates the phenotype of a large cohort of nociceptors, a finding with implications for pain therapy.

Runx1 Directly Promotes Proliferation of Hair Follicle Stem Cells and Epithelial Tumor Formation in Mouse Skin

“…Here we confirm this Runx1 expression pattern in human anagen HFs using the anti-Runx1 antibody created in the Thomas Jessell laboratory (Fig. 14A) (10). In addition, we showed that Runx1 was expressed in human telogen HFs in epithelial cells at the base of the bulge and in the secondary hair germ, just as we had previously reported in the mouse (Fig.…”

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

“…Another study also demonstrated mRNA and functional -opioid receptors in rat pups between P6 and P14 (Takeda et al, 2004). In mouse, the postnatal expression of -receptors in a subset of DRG neurons seems to be regulated by the transcription factor Runx1 (Chen et al, 2006). There are some phylogenetic differences in opioid receptor expression in the spinal cord and DRG across mammalian species.…”

Plasticity of DNA methylation in a nerve injury model of pain

“…Runx1 determines the nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain. 25 Other Runx proteins have been reported to control the axonal projection of proprioceptive DRG neurons. 26 Hypermethylated alive deserts were enriched for SOX gene family (P < 10 ¡51 ) and neurofibromin 1 (NF1) binding sites (P < 10 ¡22 ).…”