Praise for Francis Crick

One of Dr. Crick’s first publications on the role of the insula in pain was here at painonline. His radical ideas are not radical any longer. He appears to have hit the nail on the head. What is astonishing is that when Crick was the “World’s Best” at DNA molecular biology (Nobel Prize) he left the field for brain science. When he wrote for us, he was in his late eighties, had terminal cancer, and was himself in PAIN, no doubt a factor in his condescension to contribute to our group. it is sad to lose our champions. Bonica, Wall, and Crick seem irreplacable, but they have blazed the way to the lair of pain. Hearing the pain hunters in the distance, it must surely sit skulking, damaged and sensing its final fate.

The dysesthesia of Central Pain is basically an acid pain, so we like to see articles which reduce pain to that elemental quality. Additionally, we credit scientists who spend time on study design to allow for their own mistakes before they publish. Both things are combined in this recent article:

“The unpleasantness of tonic pain is encoded by the insular cortex”
M. Schreckenberger, MD, et al. Johannes Gutenberg-University Mainz, Germany. NEUROLOGY 2005;64:1175-1183.

Although the authors use the term “tonic” through some convention familiar to them, it is not clear what is actually meant. Does it refer to pain related to muscle tone or does it refer to static pain? “Phasic” pain refers to pain from rubbing or brushing, so tonic probabably here means a state which resulted from injection of acid. We cannot settle this, but do take notice of the specifics of the muscle pain, as noted below.

We do love the Germans for their precision in things. Here is what Schreckenberger found. Using F-18 fluorodeoxyglucose PET activation scans, pain from injection of an acid were compared as to readable metabolic reactions in the brain. For decades we have heard that pain is in the anterior cingulum, the frontal cortex, even the parietal cortex.

Most of the articles claiming pain is psychological cite activity in the prefrontal cortex (where emotion is encoded) as evidence that chronic pain is emotional (verging on imaginary). Some imagers even cited effects on the prefrontal cortex as evidence of the effectiveness of placebo, drugs, or whatever. Now it appears that the prefrontal cortex doesn’t tell us much about the unpleasantness of pain and is certainly not the place to tell us if placebo does any good.

If they want to accuse us of malingering, they must now deal with the insular cortex. This is a study on nociceptive pain, but there is considerable evidence that similar pathways encode (express) the neuropathic central pains.

Dr. Francis Crick shook a few heads when he invited us to publish his opinion that the “painfulness” of pain is encoded in the INSULAR cortex. This is the area which is more or less hidden under areas of overgrowth by the parietal cortex. Is is an “island” of brain surface, which is “out of sight” but definitely not “out of mind” when it comes to pain.

In the instant study, Crick’s theory came out smelling like a rose. The investigators gave both real and sham injections of acidified phosphate buffer (pH 5.2, which is about equal to the pH of fluid under a blister) and sham injections of the same phosphate buffer, with pH adjusted to 7.3, or physiologic levels, both intramuscularly and subcutaneously.

Their results are surprising in a way. The cingulum, prefrontal, and parietal cortex lit up with both real and sham injections, but only the insula avoided the power of suggestion. Only with the real acid injection did the insula light up, it showing no particular interest in sham injections of a non painful chemical. The really interesting result was that the acid gave a greater response with IM injection than with skin injection. We have always felt that the sensory arm of the gamma motor system was too much ignored, despite the copious presence of C fibers (known to be associated with the anatomic substrates of Central Pain).

The authors concluded that “the data suggest that the insula represents one main structure where the unpleasantness of tonic pain perception is encoded.”

We love this kind of work and congratulate the authors. What makes us curious is the finding that muscle pain and skin pain probably differ in where the brain handles it. This is of no small interest to us since the survey results show unequivocally that the muscle pains of CP often respond to opiates while the dysesthetic burning in the skin does NOT.