The puzzle is starting to show something. The pieces are fitting together.
During the fifties, there was an anticipation as scientists began to identify the sequence of the clotting factors. By the early sixties, it was no longer a mystery. It took thirteen steps for blood to clot. Each step had co-factors. However, when it was done, it was done. No more secrets. Lots of drugs emerged to manipulate the clotting scheme. Now, we can even inject medicine into a stroke victim and if it goes in within four hours, the clot can be dissolved and the patient will recover. Some interventionial radiologists are reporting recoveries when the drug is given within FIVE hours. It makes all that work on the clotting sequence worthwhile.
We are in pain research about where unraveling the clotting cascade was in the fifties. We know the players, but we don’t know the sequence and we don’t yet know the “cofactors” which are necessary for each step in the stepped chemical pain cascade.
One of the principles that had to be abandoned, and unfortunately KEEPS having to be abandoned, by those caught in disbelief and old medical journals, is that morphine stops nerve injury pain. Morphine CAUSES neuropathic pain. This idea is just so radical that people refuse to believe it. Some diehards believe if you have a white coat you can believe whatever you want. Their disbelief doesn’t change things however.
The pain which morphine causes is thermal hyperalgesia, a BIG, BIG part of central pain. Because the SCI sites include people who are dealing with other types of pain which ARE benefitted by morphine (opiates), such as posterior column (lemniscal) pain, such as the muscle and lightning pains, plus any nonneuropathic pain. Morphine at sufficient levels also sedates people and as anyone with Central Pain knows, sedation is beneficial to even the burning of CP. However, there are better and less addictive sedatives than opiates. It is not that we object to these patients getting whatever helps them.
As a stopgap, opiates are not so bad, but we get a lot of letters from people who find it doesn’t work in a legal environment where they cannot reliably continue to get opiates, so they have to go through detox, which is very difficult. Both patient and doctor risk going to jail if things don’t work out well in such a strategy. Ron Melzack reported a patient whose life was terrible. He got on opiates and began to work, had a girlfriend, etc. Then, when the opiates were cut off he sank back into terrible depression and pain, lost his girlfriend, job etc.
Dr. Melzack asked what was so bad about morphine if it could be medically regulated in severe CP cases, if it allowed function. Admittedly there was deep addiction. This was problemmatic mainly because the drug would eventually have to be stopped. And so, it is NOT a viable option socially, so why do physicians bother to start the drug. We are aware of patients in Canada who have relied on opiates for very long periods of time, but even there, eventually, they get cut off and at that point they are very vulnerable to ending their lives. They have carved out a method of coping and can think of no other. We want doctors to objectively realize that any benefit to BURNING pain is sedational in nature and not directly analgesic. It is just too hard for some clinicians to do a one-eighty and realize morphine is NOT the answer for burning dysesthesia. Those who use it get doped up and are sedated, but they confuse this with relief of the burning pain. This keeps the homefires burning of the diehard opioidophiles who just can’t quit pushing opiates for any and all pain. Sorry, Charlie, NO CIGAR.
We start by reminding you what is meant by neuroplasticity. It means “change in the neurons” generally hyperexcitability. This is accomplished by chemical change, usually associated with change in the rates at which genes in the cell produce peptides which become pain exciter proteins of various kinds.
We were among the first to report on Orexin’s role in neuropathic pain. Now Borgland at UCSF has learned that Orexin A in the ventral tegmental area (VTA) enhances n-methyl-D-aspartate receptor (NMDAR) transmission through a phopholipase C/protein kinase C dependent injection of NMDARs into the synapse of dopamine neurons in the VTA. VTA dopamine neurons are responsible for cocaine induced excitation, so of course this study gets funded, and of course the role of Orexin signalling in pain neurons has NOT gotten funded. The “War on Drugs” is politically correct, the war on pain is not. However, we can figure out that something comparable goes on in pain. (See prior article at this site on Orexin and pain)
You can see Borgland et al’s report in Neuron. 2006 Feb 16;49(4):589-601.
The really exciting thing about these articles is that it helps us fit pieces of the puzzle together. The Purine 2x receptor is also being widely studied and almost certainly is also amenable as a place at which pain could be blocked. The frustrating thing is that once we see the big picture, there will be dozens if not hundreds of pain medicines developed, some of which will emerge as the most effective at treating chronic nerve injury pain. We may well ALREADY HAVE the treatments, but we need funding to flesh out the findings.
We believe it is inhuman to allow unnecessary suffering and wrong to be indifferent. It is time to worry a little less about the snail darter and a little more about human beings in terrible pain. We are all for biodiversity, but knowledge in the biological sciences spreads around rather quickly. DNA work is so strong that the time is not so far away when we can MAKE snail darters. However, we can never undo the agony and suffering of those with severe Central Pain. Isn’t it time these studies began being funded for their pain value, rather than some war on drugs. How about a war on pain?
And just in case you missed it early in the article, morphine excites thermal hyperalgesia, so don’t get off on the wrong track. Opiates are not a cure all for pain. You are not a loser if morphine doesn’t help you. We need to improve on what the Egyptians knew four thousand years ago, that poppy extract helps pain. Surprisingly, we may do it by learning what the Romans knew 3500 years ago, that Euphorbia helps pain, Euphorbia being the little dwarf cactus which grows at the edge of the Sahara in Morocco, and whose latex sap yields resiniferatoxin (RTX).
Pain has never been very important except to those who had it, and for them, it was the ONLY thing that was important. Odd, isn’t it. The pain cascade…the pain cascade! Once we have it, pain will no longer have us. Pain will not be missed, and “God’s will” will not have been frustrated. You know, the pseudo-God’s will which misguided clerics imagine is God’s wish for his children at all times and in all places. The scriptures teach the exact opposite of course, but this has never deterred those who smugly saw the suffering and concluded the sufferers deserved it and needed it. We KNOW what God’s will is concerning that point of view. Hypocrisy, self-righteousness, ingratitude, and piety are not big on HIS list of valued attributes.
