In key experiments, the researchers measured the Runx1-deficient animals' response to four types of pain--thermal, mechanical, inflammatory, and neuropathic.
The researchers produced a pain response by subjecting the animals' hindpaw to either the cold of acetone or an uncomfortably warm plate (thermal); the uncomfortable prick of a filament (mechanical); an injection of an inflammation-inducing chemical (inflammatory); or nerve damage (neuropathic). They quantified the animals' response by measuring how long the animals lifted or licked their affected paw in response to the treatments.
Ma and his colleagues found that, while the deficient animals showed normal response to mechanical pain, they showed significantly lowered thermal, neuropathic, and inflammatory pain response.
The researchers concluded that while the diverse specialized components of the pain-sensing machinery could be established in a piecemeal fashion, "Our data, however, provide strong evidence that Runx1 is required to specify the receptive properties of a large cohort of nociceptive sensory neurons." They also concluded that the dual functions they discovered for Runx1--controlling specification of sensory neurons and regulating how they target their wiring--"form a genetic basis for the assembly of specific neural circuits for nociceptive information processing.
"Finally, the identification of a core transcriptional control program for many of the ion channels and receptors known to transduce noxious stimuli has intriguing implications for the design of more effective pain therapies," they wrote.