The National Institutes of Health has stated that since no satisfactory treatment exists for central pain, the CP subject should avoid stress wherever possible. Ever wonder what mechanism might lie behind this?
Remember the Eagles’ song, “Taking it Easy, taking it easy, don’t let the sound of your own voice drive you crazy”. Peace, silence, repose, and calm are often better than a bucket of pills.
There are a lot of things to get worked up about in central pain. The burning pain is the most obvious one, (along with all the other punishing and ghastly central pains). The sensory/motor losses which accompany CP and cause fumbling and immobility are also heartbreaking.
Some of the unobvious irritants seem to crop up fairly often and land pretty hard. In CP patients with loss of working memory, there is also mental agitation when required to change mental directions suddenly by the movement or speech of another individual, not unlike the agitation experienced when a routine must be broken by those with Asperger’s autism (see ilnks between autism and CP using SEARCH at this site) or in schizophrenia (see using SEARCH).
WHAT PART OF ME GETS EXCITED?
The sympathetic nervous system is one arm of the autonomic or unconsious nervous system (the other wing is the parasympathetic). Autonomics are not to be confused with the vagus nerve, the tenth cranial nerve, confused with autonomics because it also supplies the heart and gut and seems uncnnscious (are you really conscious of it when your heart slows down). The vagus (and possibly also the autonomic system) is thought to be a BYPASS for cord injury, and therefore a possible route for evoked central pain to reach the brain when the cord has been severed. (It may also be the initial bypass which brought injury to the thalamus, but that happens and then stays in place). “Vagus” means “wanderer” in Latin and this nerve certainly does do that. Generations of medical students have wondered how a cranial nerve winds up supplying heart, gut, etc.
The sympathetics are divided into several types of receptors (which also have their subtypes). the adrenergic (for adrenaline) and muscarinic. There are also cholinergic and serotonergic receptors, but we are not dealing with them here.
The adrenergic is then divided and here we are concerned with the alpha(2) adrenergics. The sympathetics are the “flight and fright” system, and of course adrenaline is what is released when you get all worked up. Actually adrenaline cannot do anything without Angiotensin II (comes from liver and lung converting enzyme), which is linked to prostaglandins. Prostaglandin is the precursor or arachidonic acid (one of the well known eicosanoid pain chemicals), from which are derived some of the acidifiers which hypersensitize the dorasl root (sesnory root) ganlgion and the dorsal horn of the cord in Central Pain.
Forget about that for a while and just remember that if you get stressed, or do anything that causes adrenaline release, your central pain will be WORSE. More adrenalin, more activity in the nervous system, and that spells trouble for someone who needs to keep the CNS QUIET!
Here we review an article on alpha(2) adrenergic pain inhibition which may shed some light on just why that might be. Sometimes we use big words but you can look past them for the useful concept. Here we must use the word “adrenergic”. Students of physiology will recognize this as one type of receptor in the sympathetic nervous system.
We have written here before on a descending pain inhibitory (antinociceptive) area which lies in the brainstem.
We explain this article in some detail because it is essential when reading drug manufacturs product information not to get taken in by claims which have never been proven clinically in double blind studies.
When medicine is injected directly or locally into nervous tissue, the effect can sometimes be the opposite of injecting it intravenously or even intrathecally (into the spinal fluid). The reason is that the neurotransmitter is NOT the story, the receptor is. Furthermore, there are usually several types of receptor for the same chemical. This concept cannot be overstressed. It is not enough to say that a drug blocks NMDA, because such a vague statement is just not specific enough. What ELSE might that drug do? Ditto for stimulating GABA. We must know which receptor the drug is directed at before we jump on the bandwagon and start spending loads of cash, assured that some drug is the answer. We need to know WHICH receptor is being blocked and WHERE.
Noradrengergic receptors are those which repond to noradrenaline, also known as norepinephrine. Wei and Pertovaara in Eur J Pharmacol. 2006 Sep 8 (in Finland) found that the pons (part of the brainstem) has an area near the locus coeruleus and lateral parabrachial nucleus where noradrenergic receptors (specifically, the adrenoreceptor type 2) exert a marked antinociceptive (pain relieving) effect. This can be blocked with Atipamezole.
Here comes the interesting part. Pay careful attention. Atimpamezole injected directly into the pons and surrounding areas had an antinociceptive effect. HOWEVER, when atimpamezole was injected IV or even intrathecally, this blocked pain relief and even reversed the antinoiception caused by injecting the drug into the pons! The brain stem and cord are thus at odds. That is why we need to know WHERE the drug is acting. The classic mistake is to assume that something which blocks pain in the cord (eg opium) will block it in the brain, Peripheral nerve injury pain relief is NOT assurance that central pain will be helped, and in fact, the opposite may be the case.
What was interesting was the DIFFERENCE between rats given nerve injury and those NOT give nerve injury. In non-neuropathic rats Atipamezole produced reduction of thermal hyperalgesia in the NON NERUOPATHIC segment of the cord in nerve injured rats, but had no effect in non injured rats. The authors concluded that:
“…nerve injury induces a tonic (ongoing) activation of pontine alpha(2)-adrenoceptors that promotes neuropathic hypersensitivity by attenuating descending inhibition. Thus, spinal and pontine alpha(2)-adrenoceptors have opposite effects on pain-related behavior in neuropathic animals.”
We first like the article because it establishes a way a neuropathic nervous system differs from a normal one. In discussing pain relief it is important to avoid extrapolation from normals to neuropathic individuals. This distinction should head off some of the behaviorists at the pass, who attempt to use nociceptive pain studies to generalize about neuropathic pain.
Again, the Atimpamezole had NO effect on normal rats.
What this study also may mean in practical terms is that if you get very excited, your spinal alpha2 adrenoreceptors may override the efforts of the pons to exert antinociceptive effect. Becoming aware of greater pain during agitation is a common experience for central pain people and will come as no surprise. What we may be looking at here is the mechanism. One would expect emotionality or excitement to block pain awareness, and perhaps it does for a brief period, but in the aftermath, the CP sufferer will wish the excitement had been avoided. Severe central pain is the most severe pain state known to man. CP subjects live on the edge, and with the risk of self being a factor, CP patients simply must stay as far from the breaking point as possible.
CP sufferers, who generally retain some motor function, frequently encounter the unthinking remark that “You are lucky, you could be paralyzed. This ignores the obvious. Wheelchair individuals can achieve remarkable things. One of the most inspirational individuals was Franklin D. Roosevelt, paralyzed by polio, but still able to be President of the United States, in a difficult time during WWII. Those with severe CP cling to life, unsteady, halting, and grimly determined. Central Pain is worse than paralysis. Unending severe pain is worse than anything. That is why such pain is always used as a metaphor for hell (we hope it is a metaphor!). Many religions also rate severe physical suffering as the test of tests. Having brains, we don’t really need religion to tell us that.
However, there is no excuse for not vigorously researching spinal cord injury either. We have the word of nearly one thousand survey respondents on that. No one who rates their central pain as severe puts any paralysis on the same plain. As Beric has pointed out, when severe CP is in the muscles, it may CAUSE paralysis because the pain of movement is too great. There are leagues of CP subjects who are not paralyzed but pay a price in muscle pain for every movement.
What is important is that you learn NOT to accept articles which fail to differentiate routes of infusion, area of infusion, and recheck with blockers in all circumstances. This is so important but is a step omitted all to frequently in drugs pushed to the public with glib mention that it works by “affecting” NMDA, GABA, alpha 2 adrenoreceptors, or whatever.