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Scientists Create Mice That Can’t Feel Cold

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[Source: Wikimedia Commons]

Hate the cold? Always feel like the room's chilly while others inexplicably seem nice and comfortably cozy warm? Here's one extreme solution to take the chill off. Scientists created a group of mice that were incapable of feeling cold by killing off the neurons in the body whose specific job it is to transmit cold sensation from the skin to the brain. Rather than an attempt to create an X-men-like mutation, the study sheds light on how the nervous system transmits sensory information from the body to the brain and may help to develop more sophisticated pain medicines.

Our sensations are transmitted from our skin through different neurons that are fine-tuned for specific sensations, such as hot or cold, touch, or pain. Which sensation or sensations a neuron transmits is determined by the type of protein receptors it expresses. And while there are several types of receptors that respond to heat, it turns out that mammals have one main receptor for cold detection called TRPM8, part of the transient receptor potential (TRP; pronounced “trip”) family of proteins that act as molecular thermo-detectors.

To study how cold is processed by the nervous system, the scientists used a toxin to kill all TRPM8-containing neurons in the mice. To test how the absence of the neurons affected their ability to detect cold, the mice were placed on a surface that ranged from 0 degrees Celsius at one end to 50 degrees at the other (32 to 122 degrees Fahrenheit) where they were allowed to move freely. Normal mice with all their neurons, not liking it too hot or too cold but just right, would tend to end up at an area where the temperature was a cozy 30 degrees Celsius (86 degrees Fahrenheit). The mice without TRPM8 neurons, however, avoided the hot area of the surface but did not avoid the colder areas, even areas near freezing where the surface should have been painful. Without the proper neurons, the mice couldn’t detect the cold. In another set of experiments, the scientists showed that cold no longer relieved pain in the TRPM8-lacking mice. Importantly, the mice’s ability to sense touch, heat and body position remained normal.

David McKemy hopes that his group's research will one day lead to pain medication that treats pain in a more targeted way. [Source: USC Dornsife]

The study was published in the February 13 issue of the Journal of Neuroscience. Led by David McKemy, associate professor of neurobiology at the University of Southern California Dornsife College of Letters, Arts and Sciences, the study was motivated by a desire to disentangle how different types of sensory information – hot, cold, pain – are processed by the neurons under our skin and then later by higher centers in the brain. McKemy hopes the research will help develop more nuanced pain treatments. “The problem with pain drugs now is that they typically just reduce inflammation, which is just one potential cause of pain,” he said in a press release, “or they knock out all sensation, which often is not desirable. One of our goals is to pave the way for medications that address the pain directly in a way that does not leave the patients completely numb.”

It’s probably up in the brain’s higher processing centers where the explanation for bizarre cases like Wim Hof and Lynne Cox exist. Hof, aka “The Ice Man,” is a Dutch man with an extraordinary ability to control his body’s normal responses with his mind. It allowed him to trek up Mount Everest wearing only shorts. “It was easy,” he says. And Cox, who crossed the English Channel in record time and, in 1987, became the first person to swim across the Bering Strait through near freezing waters (less than 4 degrees Celsius, 38 degrees Fahrenheit). Scientists continue to study these X-men-like phenoms, but with few new insights. Scientists can only guess that there’s some strange wiring in Hof’s brain that explains his ability to control, not only his own body temperature but his autonomic nervous and immune systems as well.

Pain is a good thing, it tells us when we’re likely to be injured and so helps us to avoid it. Chronic pain, however, serves no useful purpose and can drastically reduce a person’s quality of life. By studying pain at the extremities, as in the current study, and the higher brain centers of people with extraordinary abilities to suppress pain, we maximize the chances of finding pain relief for everyone.

Peter Murray

Peter Murray was born in Boston in 1973. He earned a PhD in neuroscience at the University of Maryland, Baltimore studying gene expression in the neocortex. Following his dissertation work he spent three years as a post-doctoral fellow at the same university studying brain mechanisms of pain and motor control. He completed a collection of short stories in 2010 and has been writing for Singularity Hub since March 2011.

Discussion — 3 Responses

  • DigitalGalaxy February 25, 2013 on 2:43 pm

    Not a fan of this research. We need to stop doing animal testing for everything but the most life-saving medications. Sure we might get something useful out of this, like better pain medications, but we have to balance the results we get from the suffering and harm we are inflicting on the animals we test. Right now we don’t really take that into account, and we are willing to inflict extreme pain and harm for something as non-life threatening as cosmetics.

    I’m certainly not against better pain medications, but I am against this moral blind spot that we as a people still have towards lower animals. If at least there was some calculation that we make in the future, such as “we are attempting to extract X benefit for humanity from this animal torture”, and “we are going to inflict Y amount of suffering”, is this research able to proceed? Some way to examine our behavior. Right now we treat animals like they cannot feel the pain we inflict in our experiments, like disposable machines. They are not.

    Our computer models are only getting more an more powerful and more and more accurate. Soon we will be able to simulate direct protein interaction with good enough models, and we are still testing on lab rats? Killing cold receptor neurons? I know it’s in the preliminary stages, and could lead to more tangible results, but that doesn’t sound like its gathering any useful information to me, at least at this stage.

    Besides, half the time these treatments work on animals and then fail in the human body, simply because they physiology is so different.

    I would rather see human testing on patients that are fully informed of the risks, the consequences, and are rewarded accordingly before they consent to experimental treatments.

    Would you take a $150,000 reward to submit yourself to a radical procedure with no knowledge of the outcome? I wouldn’t, but I bet a lot of older people on their last legs would, as a way to finance an extravagant “bucket list” at 70.

    That might have a chilling effect on research, since it would drive the price up, but maybe the biomedical sector needs that chilling effect. I don’t think we SHOULD be experimenting on animals just because it is economical. I think we should move increasingly to computer models to do this sort of research. Our attitude towards animals is something that needs to change dramatically if we as a society want to progress. Right now we treat other species as disposable. We need to treat them with respect, instead.

    If we don’t, then what is to stop us, ultimately, from treating ourselves as disposable? If we don’t re-discover the reverence for life that we had long ago, we might end up losing our focus, and finding humans on the dissection table instead of animals. Many modern intellectual movements, (Peter Singer comes to mind) already advocate for the destruction of the mentally or physically handicapped at the early stages of life. It’s eugenics 2.0. The best way to combat that intellectually is to re-engage respect for lower life forms. And the first step in that direction is to ban animal testing, on all but the most life-saving medication.

    Sorry, Dr. Mckemy. You may one day discover a better pain medication, or more insights into neurology. But you, and the rest of the scientific community, are going about your research in a morally blind manner. You have computer models at your disposal, use them instead; even if they aren’t as good, or need constant tuning to more accurately represent reality.

    The rest of us need to stand up and tell the government NO to animal testing.

    The Singularity is not only about technology. It’s about how our moral systems are hopelessly archaic, and have no means to guide us in this era, no way to tell us whether what we are doing is right or wrong. We need those moral systems as much as we need faster processors, Mars colonies, and brain-computer interfaces. If we don’t get them…we run the risk of finding ourselves in a dystopia instead of a utopia.

    • Håkon Tjeldnes DigitalGalaxy February 28, 2013 on 3:12 pm

      Mice do experience the qualia of pain as we do, but I do, and someday I might want have this medicine. Therefor it is morally correct science.

      Hitting a mice is like hitting a computer programed to say “ouch,” when it is touched. There is no qualia, only stimuli and respons.

      • DigitalGalaxy Håkon Tjeldnes March 1, 2013 on 12:55 am

        I beg to differ. Do you have some way of proving that mice, or lower animals in general, have no qualia? It seems irrational, for instance, to claim that monkeys, only one evolutionary step down from us, have no qualia. What is so special about humans? At what point do animals stop having the qualia that we have? Which step in the evolutionary chain breaks that continuity?

        Ask any pet owner if thier dog, cat (or even mouse!) has feelings, emotions, and sensations. They will probably say yes.

        There is no brain structure that we can point to to say, “This produces qualia here, by this chemical reaction”. No brain wave that will turn a nerve signal into the sensation of pain. The existence of qualia is something that we have no material explanation for.

        However, mice and other animals certainly act as though they have qualia. There is certainly stimuli and response, and in humans that produces pain qualia. Therefore the burden of proof is on those who claim that animals do not have qualia, to prove they do not posess them. Since there is no way to detect qualia at present, that is a burden of proof that cannot be met at this time.

        Thus, animal research remains immoral, for all but life-saving medication. We are causing suffering to animals simply for our own comfort. We should be researching this pain medicine, but not by causing animal torture. We can use computer models and well informed, well-compensated human test subjects instead.

        When you hit a comptuer programmed to say “ouch”, we know exactly what is going on inside that computer, becuase we programmed it down to the last electron, and so we can say the computer has no qualia. We did not program the mouse, we have no idea what goes on in its brain or what gives it consciousness or “soul”, if you want to put it that way.

        We have no way to tell how a pain signal turns into pain qualia. Until we do, we cannot say that animals have no qualia, so we have to treat them like respected life forms. That’s my opinion, anyway!