I’ve never been able to find a proper reference for it, but I’ve read somewhere that there is something like 72 kilometres of peripheral nerves in the adult human body. Whether this number is accurate or not, it’s safe to say that there is a lot, but with the increasing trendiness of the brain in pain research, this continuous, mechanical, dynamic, neuroimmune structure often gets forgotten.
There’s a pervasive conceptualisation out there in the general public (and large sections of the clinical community too) that equates nerves to power cords – ‘dumb’ wires that simply carry electrical signals to and from the brain. But the cord on your toaster is nothing like your peripheral nerves, which are alive, moving, always changing and constantly adapting.
If you cut the cord on the toaster, there won’t be any toast – nothing; you might as well put your vegemite and peanut butter back in the cupboard and throw the toaster away. But if you cut or damage a nerve, it will react with a complex cascade of neuroimmune responses – there will never be one molecular mechanism involved; it will be a combination of processes such local inflammation, neurogenic inflammation, immune responses, endoneurial fluid pressure changes and ion channel changes.
Additionally, there will be changes in the brain as the cut bit still tries to represent what it innervates and the brain tries to compensate and adapt. Some of these brain changes will remain long after the injury, with epigenetic changes in a number of brain areas evident 6 months after peripheral nerve injury (Tajerian et al 2013) and glial cells remaining ‘experienced’ and on alert for years (Banati et al 2001).
Nasty pain and stress states may ensue.
But there is so much rich, therapeutic narrative in the story of the peripheral nerves – take ion channels for example- there is around a million in a neurone, mostly at the terminal and nodes of Ranvier (that is how the action potential can jump over myelin). After an injury a nerve will make heaps more of these at the site of damage, all ready to act in response to mechanical, stress, immune or environmental stimuli. But these channels are turned over every few days and numbers can reflect the perceived need for protection of the human. This changeability should be a cause for hope that symptoms can and will change.
The broader stories of the peripheral nerves can help explain symptoms, inform clinical reasoning and engender wonder for the neuroimmune system as a therapeutic target.
Imagine a toaster that could repair its own cord, reorganise its heating elements and make the toast for you!
-David Butler and Tim Cocks
Banati RB, Cagnin A, Brooks DJ, Gunn RN, Myers R, Jones T, Birch R and Anand P et al (2001). Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury. Neuroreport 12(16) 3439-3442.
Tajerian M, Alvarado S, Millecamps M, Vachon P, Crosby C, Bushnell MC, et al. (2013) Peripheral Nerve Injury Is Associated with Chronic, Reversible Changes in Global DNA Methylation in the Mouse Prefrontal Cortex. PLoS ONE 8(1).
(Full references available at links above)