Neuropathic Pain, a generalized condition.

In the past, there has often been an attempt to link specific pain with specific lesions. New PET studies show this is not always the case, and possibly never fully the case.

We have emphasized before that injury spreads. The release of chemicals from injured nerve tissue travels outward, apparently for quite a distance.

This was illustrated recently by Marrawi J etal Pain. 2006 Nov 28 “Differential brain opioid receptor availability in central and peripheral neuropathic pain.”

Marrawi used 11-C labeled diprenorphine (an opiate) and PET scans to show markedly decreased ability of opiate receptors to bind to opiate in nerve injury. The subjects were those with peripheral nerve injury and those with post stroke pain. No post SCI patients were included.

It was found that opiate receptors in the BRAIN were unable to bind opiate well BILATERALLY. By comparison, post stroke patients’ brain could not bind on the side of the brain opposite to the manifestations of pain. Pain crosses over after it enters cord, so the crossed hemialgesia is to be expected. (stroke on left brain causes skin burning on the right side of the body and vice versa).

The decreased binding was found to be present in:
“posterior midbrain, medial thalamus and the insular, temporal and prefrontal cortices contralateral to the painful side”.

Most importantly, the SIZE of the brain lesion did not correlate with the severity of the pain, NOR did the location of the pain co-locate with the area of the brain which was injured. In other words, something had been released into the brain generally on the side of the stroke which took its own course and affected opiate binding in a manner independent of other functions lost and also independent of how large the area affected by the stroke.

What this tells us is that our doctors will never be able to be anatomists, because there is too much chemistry going on. She will not be able to say, “You have pain here because you are injured there.” Instead, our doctor can only surmise how the cascade of pain chemicals has been altered by brain plasticity. In the past, too many patients were disbelieved or even mocked when their area of burning did not cleaning match the level of the lesion or the size of the lesion.

They were also disbelieved unless “the lesion” could be seen on MRI. We have already pointed out that MRI can only resolve about 1.5 mm. which is larger than the entire spinothalamic tract. Furthermore THE ST tract is not really in one place, it is more like telephone wire, winding up through the cord to the thalamus. Injury to one of those contributing branches would be sufficient to cause central pain but this would most certainly not show up on MRI. Dr. Pat Wall used to say that bright lesions on MRI, when they are present, may not even be showing the injury which is causing the central pain, which may be MRI invisible. The IASP has published a study by Dr. K. McHenry giving similar interpretations of the disconnect between anatomic location of injury/imaging study patterns and the anatomic location of some of the pain symptoms.

Again, the diagnosis is made by history, which is most unique, and not by imaging studies. The location of the pain will never quite seem anatomical and thus we have patients afraid to tell skeptical doctors what is really going on in their bodies, their memories, and their emotions. Studies like those of Marrawi will hopefully do much to assuage the misunderstanding. It will also explain why so many CP patients are unresponsive to opiates. Dr. Howeard Rowbotham has suggested that these same patients might respond to VERY HIGH levels of opiates, but who is going to prescribe them and how will side effects be handled.

Fortunately, binding is something which biochemists can play with and improve, leading to the possibility of help. We already have such drugs in the form of things like fentanyl but the addictive tendencies surely limit the usefulness of such drugs. We need strong binding, and less addictive tendency if opiates are to be of help to very many CP patients.