Cold sensing neural¹ circuits（神经回路） in newborn mice take around two weeks to become fully² active, according to a new study. The finding adds to understanding of the cold sensing protein TRPM8 (pronounced trip-em-ate), first identified in a Nature paper in 2002 by David McKemy of the University of Southern California.

McKemy's latest study, published online by Neuroscience, shows that the cold sensing circuit starts to develop in utero（在子宫内，出生前） but does not mature until well after birth.

"About three or four days before the animal is born, the protein is expressed. However, the axons（轴突） of these nerves going into the spinal³ cord are not fully formed until probably two weeks after birth," McKemy said.

The delay in development of cold sensing is plausible⁴（貌似真实的） , McKemy added.

"In the womb（子宫） , when would we ever feel cold?"

By contrast, mice are born with a keen sense of smell, which they need to breast feed successfully.

Direct study of the cold sensing protein TRPM8 in humans is not yet possible. While sensory⁵ development differs in mice and humans – mice are born blind, for example – the study suggests a possible biological basis for findings of altered cold sensitivity in children.

In a 2008 study of temperature sensation by the Institute of Child Health at University College London, researchers found that 11-year-old children born prematurely⁶（过早地，早熟地） were less sensitive to temperature than those born at term（到期） .

"This is consistent with our observations that the circuitry is not fully developed until after birth, thus anything that disrupts this formation at this important stage could have long term effects," McKemy noted⁷.

"There are other reports that injury and inflammation in rodent⁸（啮齿动物） models that occur during the (prenatal) period lead to altered temperature sensitivity as well as altered neural circuits."

The USC researchers tracked development of cold sensing through mice genetically⁹ engineered to express a green fluorescent¹⁰（荧光的） protein whenever TRPM8 was produced.

TRPM8 is one in a class of proteins known as ion channels（离子通道） . Their purpose is to "turn on the cell" when they receive a stimulus¹¹. TRPM8 senses both painful cold and the soothing¹²（使人宽心的，抚慰的） cold of menthol-based creams.

How one protein can convey both sensations is unknown. McKemy speculated that neurons differ in their internal architecture, with each tuned¹³ to accept either painful or pleasant cold signals from TRPM8.

One goal of TRPM8 research is to understand the molecular¹⁴（分子的） mechanisms¹⁵ of sensation, in the hope of developing better drugs for relief of chronic¹⁶（慢性的，长期的） pain states, such as the extreme sensitivity to cold experienced by some diabetes¹⁷（糖尿病） patients.

"If you want to understand conditions like cold allodynia（触摸痛，异常性疼痛） , which is cold pain, you need to find exactly what are the targets," McKemy said.

"If we understand the basic nuts and bolts（具体细节，基本要素） of the molecules¹⁸ and neurons and how they detect pain normally," McKemy said, "then perhaps we can figure out why we detect pain when we shouldn't."