Two Possible New Treatments, a Confirmation of the Surveys

The workhorses of pain research, so long hobbled by lack of technology, are proving to be the best guides for the young turks who handle the new machinery. We finally have dynamic radiologic imaging of pain to silence the scoffers and doubters. We express gratitude to both groups for sticking with it. We assure you, Central Pain is real, and it is torture. The pain you see on your MRI screens, we feel every moment. Please help us.

The number of articles at painonline on the links between fatty acids/lipids and pain is extensive. This work is now being played out in lipid studies.

For example, T. P. Malan, et al, writing in Prostaglandins and Other Lipid Mediators, Sept 2005 pp. 123-30, has now identified six specific lipids involved in pain modulation. Most importantly, they have also shown that the acylethanolamides inhibit pain response.

The strange thing is that whenever we find a chemical which does something in the body, there is generally a close structural mimic which blocks that chemical or even actively inhibits the same process.

The six lipids are,
2)phosphatidyl inositol biphosphate,
4 and 5)lipoxygenase metabolites of arachidonic acid(2) which come from triglycerides in the body released by lipases and in the pathway to form leukotrienes, which are found in the thalamus in central pain according to Tarek Samad’s work at Harvard,
6)and fatty acyl dopamines

Dont get mystified, these are just fatty acids with their hair combed differently. They curl back on themselves either due to the stiffness of sulfide bonds or the laxity of isoleucine which allows twisting around corners. Proline has a weird triangular bend which also allows the loops like folding hoses to lay on the grass. Isoelectric amino acids sit in the inner core of proteins to excape degredation by water. This is the opposite of membranes, where the fatty water avoiding parts stick out on the surface. The little domains that make up proteins make them take shapes that look like small machines, and in fact they are. The shape looks like a chinese puzzle, with helixes and ribbons here and there. These proteins are what make us tick, not our imagination. The pain lipids come from twenty long peptides of amino acids and then tend to turn into a circle. An amino acid typically has an amino group at the left which can supply a proton and an COO- group at the right end. Bonds from right of one to left of the next are called peptide bonds and they are strong, tending not to rotate. Even cooking these proteins tends NOT to affect the shape. Configuration of any protein, which is necessary for function depnds on other bonds. In the case of helical loops, each turn takes up about 3.6 amino acids and the loop above forms hydrogen bonds with the loop beneath, stabliizing the precarious looking structure. This is the alpha helix. Ribbon looking groups tend to fold en masse and are called beta configurations. They look like folded window shades. Human amino acids tend to trail off to the left in their structure (L), while bacterial amino acids are the mirror image, but trail off to the right (D). This difference allows potent antibiotics to be used against bacteria, which D structures have no effect on humans who can only use the D enantiomer. Mixes of D and L are called “racemic”. The newer better medicines purify the L from the D.

Most of these lipids are reviewed elsewhere at this site. We now believe that these six increase the pain response. We especially welcome the work on acylethanolamides, blockers of the action of the six, as giving promise of a new class of possible treatments for pain of nerve injury.

A second front in new research concerns the chemicals manufactured by the skin of certain frogs. L Negri et al Aug 22 2005 Brit J. Pharm, have found that Bombina variegate secrete a small BV-8 protein which modulates pain and causes MAPK phosphorylation and current in the Calcium 2+ channels. (See MAPK using search elsewhere at this site). Similar to the counterfeiting blockage mentioned above, attachment of a side chain stops the action of this pain process. Des-Alanine, Valine BV8 was capable of blocking pain activity. it remains to be seen what other pain processes might be blocked.



Central Pain has been broadly grouped into the spontaneous pains and the evoked ones. This differentiation was noted by Mitchell but specified in modern times by Ron Tasker. Other differentiations have been based on whether the pain was carried in the front of the cord or in the back of the cord. This latter differentiation is a presumption but so far we are batting a thousand on the fMRI and PET studies.

We have long indicated that the central pains differ, based solely on the answers to surveys in the Wall/McHenry database. Now Maihofner along with the famous pain researcher HO Handwerker, at Erlangen Germany, have shown a distinct difference between ongoing (spontaneous) and stimulus induced pain (evoked). Stimulus induced pain can be divided into PRIMARY and SECONDARY hyperalgesia (increased gene expression of pain exciter chemicals in the cord). The primary is associated with thermal or heat hyperalgesia while the secondary is associated with touch, mechanical, or pin prick hyperalgesia. Both of these modalities are thought to be carried in the front of the cord (spinothalamic tract) and to be set off by C fiber activity, which is related to TRPV-1 receptors, which use the Ca2+ channels.

What is remarkable is that these two hyperalgesias have now been separated from each other using functional MRI. It has never been settled which type of pain is carried in the anterior spinothalamic tracts and which is carried in the lateral spinothalamic tracts. These tracts are located in the front of the cord, and studies have been done in non humans. Because of this, most researchers speak as if there were only one tract. Perhaps tensor analysis tract tracing will finally answer this matter in humans, but the work has not been done.

Secondary or mechanical pin-prick hyperalgesia (before and after capsaicin exposure) led to