Characterization of two Runx1-dependent nociceptor differentiation programs necessary for inflammatory versus neuropathic pain.
BACKGROUND
The cellular and molecular programs that control specific types of pain are poorly understood. We reported previously that the runt domain transcription factor Runx1 is initially expressed in most nociceptors and controls sensory neuron phenotypes necessary for inflammatory and neuropathic pain.


RESULTS
Here we show that expression of Runx1-dependent ion channels and receptors is distributed into two nociceptor populations that are distinguished by persistent or transient Runx1 expression. Conditional mutation of Runx1 at perinatal stages leads to preferential impairment of Runx1-persistent nociceptors and a selective defect in inflammatory pain. Conversely, constitutive Runx1 expression in Runx1-transient nociceptors leads to an impairment of Runx1-transient nociceptors and a selective deficit in neuropathic pain. Notably, the subdivision of Runx1-persistent and Runx1-transient nociceptors does not follow the classical nociceptor subdivision into IB4+ nonpeptidergic and IB4- peptidergic populations.


CONCLUSIONS
Altogether, we have uncovered two distinct Runx1-dependent nociceptor differentiation programs that are permissive for inflammatory versus neuropathic pain. These studies lend support to a transcription factor-based distinction of neuronal classes necessary for inflammatory versus neuropathic pain.
Abdel Samad
Omar
O
Department of Neurobiology, Dana-Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.
Liu
Yang
Y
Yang
Fu-Chia
FC
Kramer
Ina
I
Arber
Silvia
S
Ma
Qiufu
Q
D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology*; D055495:Neurogenesis; D009619:Nociceptors / Q000378:metabolism / Q000473:pathology*; D015222:Sodium Channels / Q000235:genetics
D050676:Core Binding Factor Alpha 2 Subunit; D062559:NAV1.8 Voltage-Gated Sodium Channel; C493726:Runx1 protein, mouse; C568318:Scn10a protein, mouse; D015222:Sodium Channels