Monday, 11 December 2017

Temperature dependence of impulse conduction in optic nerve axons

Thanks for the comments
We were grateful when a number of readers responded to our enquiry regarding temperature dependent symptoms in MS, and we learned more about how people cope with the symptoms. Following this conversation, I thought it worthwhile to draw attention to a paper we recently published, that suggests that there are functional differences between normal peripheral and central axons, and these differences provide a new view on temperature sensitivity.   

Optic nerve amazingly sensitive to changes in temperature
A few years ago, my colleagues and I found unexpectedly that the function of rodent optic nerve axons, maintained in a nerve bath, is amazingly sensitive to temperature changes. The nerve bath that we use is a chamber in which a nerve can be maintained with nutrient and oxygen outside the body. The comparison we were subsequently able to make with normal sensory axons in the human hand in vivo, with a colleague at the University of Sydney, makes it look like the phenomenon is one that affects the optic nerve (and therefore potentially central axons more generally) but not the peripheral nerve. One of the advantages of doing experiments in a nerve bath is that one can control temperature really precisely, and also the application of drugs to the tissue. Since then we have tried to confirm that the temperature sensitivity really exists, and we have done it a number of ways now, so at least in terms of our experimental preparation there seems little doubt it exists, and secondly we have been trying to find out what the mechanism of such sensitivity might be. This is the paper: Diuretic-sensitive electroneutral Na+ movement and temperature effects on central axons by Meneka Kanagaratnam, Christopher Pendleton. Danilo Almeida Souza, Joseph Pettit, James Howells and Mark Baker. Journal of Physiology 595.11 (2017) 3471-3482.



Ideas about the mechanism of temperature sensitivity
The way I became aware of temperature dependent symptoms was initially through the work of Hugh Bostock, where he used a peripheral nerve model of demyelination, and demonstrated conduction failure in single axons when raising temperature acutely. There is a classical explanation for this, based on work done by the Nobel Prize winners, Alan Hodgkin and Bernard Katz. The classical explanation says that the nerve impulse gets briefer when the axon warms up, and this brevity means that the impulse is more likely to fail at sites along the axon that have been damaged by demyelination. Of course, there is every expectation that this principle is still likely applicable, but what we have found suggests that normally in central axons, as one warms up, the axons get less excitable in a way unrelated to the brevity of the impulse but for another reason. It is because the warming alters the resting properties of the axon, making an impulse harder to generate and also harder to propagate (ie to jump along). In normal axons, this effect of warming we would suggest is within the tolerance of the nervous system, and symptoms don’t appear. (That said, it is common knowledge that relatively minor rises or falls in core body temperature in fit and healthy people can dramatically alter properties of the nervous system, including causing loss of conscious for example with hypothermia). So we could now offer an additional insight and say that where impulse conduction is touch-and-go at sites in damaged axons, one possibility is that this newly described property could contribute to make the impulse fail, and so exacerbate symptoms. We are still working on the biophysical mechanism, and once we have more confidence in that mechanism it is our hope that a route to pharmacologically manipulating the property will become apparent, and so in the future more help may be offered to people experiencing temperature dependent symptoms. 


Do you have temperature dependent symptoms that affect your vision? Those were the first temperature dependent symptoms described. Perhaps you have double vision, perhaps altered acuity? How does getting too warm affect your vision? We would value your comments

Thank you!

Mark Baker

5 comments:

  1. This was one of the very first symptoms of my MS. I didn't know I had MS back then, but when playing soccer I realised that when I was running fast for a while my vision got blurry. Later I found out I had had an optic neuritis. I don't know if I still have it because now I can't run anymore.

    ReplyDelete
  2. Temperature used to affect color vision acuity early on. Also had one episode where I developed diplopia after a spinal tap, that lasted about a week.

    ReplyDelete
  3. I do not Know if it is directly realted to the temperature or not, but want to share one experience. When I drink a very cold (nearly ice) big glass of water (33-50 cl.) my sinthoms improve very much for 1 hour aprox. When I say improve it means around at least 30% better in speed and distance walking.

    Can it been explained by somethig, it juste because of the temperature?
    Has anybody experienced somethig similar? (if not try to do it, please)

    My neuro has not any axplanation.

    Thanks

    ReplyDelete
    Replies
    1. Yes, it's very likely that this is do do with temperature.
      I'm very surprised that your neuro sems to be unaware of Uhthoff's phenomenon, it was described in 1890 (though that might be rather too recent to be accepted by some neuros!).
      https://en.wikipedia.org/wiki/Uhthoff%27s_phenomenon

      Delete
  4. Elevated temperature affects (reduces) my acuity and contrast perception.

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.