Runx1 determines nociceptive sensory neuron phenotype and is required for thermal and neuropathic pain.
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.
Chen
Chih-Li
CL
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115, USA.
Broom
Daniel C
DC
Liu
Yang
Y
de Nooij
Joriene C
JC
Li
Zhe
Z
Cen
Chuan
C
Samad
Omar Abdel
OA
Jessell
Thomas M
TM
Woolf
Clifford J
CJ
Ma
Qiufu
Q
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D050676:Core Binding Factor Alpha 2 Subunit / Q000172:deficiency / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007473:Ion Channels / Q000145:classification / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D010812:Physical Stimulation / Q000009:adverse effects; D011493:Protein Kinase C / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D013697:Thermosensing / Q000502:physiology*; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases; D051155:Wnt1 Protein / Q000235:genetics; D000070584:Tripartite Motif Proteins
D015740:Calcitonin Gene-Related Peptide; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D007473:Ion Channels; D037102:Lectins; D009687:Nuclear Proteins; D011493:Protein Kinase C; D020917:Receptor, trkA; D044767:Ubiquitin-Protein Ligases; D051155:Wnt1 Protein; C493726:Runx1 protein, mouse; C489296:Trim27 protein, mouse; D000070584:Tripartite Motif Proteins; C087857:protein kinase C gamma