We have pointed out the inability of CP neurons to manufacture KCC2, the carrier of inhibitory chloride ions. Now, it appears a CP neuron cannot bind opioids.
Writing in Eur J Pain. 2004 Oct;8(5):479-85, AK Jones etal have shown a surprising inability of CP brain neurons to bind opioids. An opioid is any chemical which displays opiate like behavior. An opiate is a derivative of opium, which comes from the poppy flower. Opiates include things like morphine and codeine.
The authors used positron emission tomography (PET scans) to show that diprenorphine cannot bind well in the brains of those with CP. Thus, it is highly likely that such people cannot relieve their own pain with endogenous opioids, nor can their pain be relieved by the external administration of opioids.
The PET scans showed decreased binding in areas well known to be involved with pain, and at many levels. This deficiency was noted not only in thalamic areas of pain perception, but also in brain areas traditionally thought to be responsible for the “painfulness of pain”
(See article with contribution by Francis Crick on the insular cortex, at this site)
Jones and colleagues found decreased opioid binding in the anterior cingulum, the dorsolateral cingulum and other important pain areas. For the purist, they found this deficiency in opioid binding in Brodman areas 10 (DL cing.), 24 (Ant. Cing.), with some decrease in 23 (an extension of 24), 40 (Inf. Parietal Cortex), the insula and the thalamus.
This finding is very consistent with the repeated reports that opiates are ineffective in Central Pain. Elsewhere at this site, we have noted that it is primarily the pains carried in the spinothalamic tracts which do not respond to opioids. Anterior cord pain has shown little benefit from any therapy. Treatment is therefore commonly directed at simply quieting the CNS, such as through the use of sedatives, clonazepam and related muscle relaxants, anticonvulsants, or tricyclic antidepressants.
The pains of the posterior cord, so called lemniscal pains, are more amenable to opioids. However, even there, CP patients probably may require higher doess. Clinicians must sort this out, and you must work with your clinician on any decisions about treatment.
Still to be demonstrated is why CP nerve cells are not rendered painless by lidocaine. Studies have differed on this important topic. The work has been almost exclusively in animals, and even there the foot pad model predominates, so it is really periopheral neuropathy which has been studied. Bupivicaine, which is slower acting than lidocaine, seems to have greater effect, but this also is unproven.
It would appear that the gene protein factories just do not work well in injured neurons. We already know that injured pain neurons produce inappropriate Nav1.3 ion channels, which should only be present in a fetus. We also know injured neurons cannot manufacture the carrier for chloride ions, preventing inhibition. Injured neurons now appear also unable to bind opioids and perhaps unable to respond to lidocaine block. (This latter statement is not confirmed, but is suspected based on unimpressive lidocaine action at the VR1 channel) Other abnormalities in injured neurons will surely be found.
In the meantime, it is utterly inappropriate to speak of will or “pain behavior” in CP subjects, until the cellular physiology which controls pain is rendered normal. or else a block of the VR1 calcium channel is achieved, at which time we suspect all talk of psychological causes will cease. CP patients cannot stop spontaneous pain signals nor utilize the methods normals use to damp or prevent pain signals.
CP is the only disease where doctors accept NOTHING from the patient until molecular studies suggest what might be present clinically. Typically, a disease is known, and then molecular studies are conducted to explain the symptoms and pathophysiology. In CP, because the work of Mitchell, Dejerine, Roussy, Riddoch, and Tasker was ignored, we have to rediscover the wheel with each generation. For example, both Dejerine and Roussy noticed that opiates had no effect on CP. Yet, this lesson seems to require a new discovery in each generation, since some clinicians have a little success with posterior cord pain and fail to realize opiates are not helping anterior cord pain. This is where the myth of the uncooperative pain patient comes in, with failure to discriminate symptoms.
The instant article by Jones should be no surprise, but it will no doubt run into much resistance by diehards who have not read the old literature. Mitchell noted a twenty second delay before tough evoked burning dysesthesia in pain of central origin, but this touch pain was instantaneous in peripheral nerve injury. Only recently have scientists begun to speak again of temporal summation, which is nothing more than Mitchell’s delay. How many times do we have to keep learning these lessons? How long before clinicians credit the painstaking work of another generation, whom they have not read.
The clinical symptoms have always been there, it is just that they seem so different from normal pain, that they have been discounted Only with the discovery of molecular behavior do clinicians take another look at patients and discover they should have expected such symptoms all along. Such is the difficulty of penetrating the curtain of ignorance about pain which has no vocabulary.