Acid Keeps Coming Up, Sort Of

Because of the persistent comment by CP subjects that the burning feels like “acid under the skin”, (or like the “indian burn” which chlidren give each other) and the discovery of acidifying agents in the thalamus of experimental pain animal models, we have watched reports on acid effects and have reported them. Here is another in that series.

The acid watch at painonline continues. See Putnam, RW et al, Am J Physiol Cell Physiol. 2004 Dec;287(6):C1493-526.

Putnam has now theorized that the effects of acid on chemosenstive cells operates via the effects on a potassium (K+) channel. This depolarizes (makes more likely to fire) a chemosensitive (sensitive to changes in pH) neuron, making pain more likely or certain to occur.

This concept promises to result in closer scrutiny for the meaning of “pain”. Is pain a perception or is there a certain characteristic of signals which might be called pain. For example. other chemosensitive neurons in the body are not always consciously felt but mediate some sort of quasi-noxious signal. Examples include “peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors”.

The question arises whether unconscious chemosensitive cells might become hypersenstive to the point that something like central pain is occurring. If so, central pain will be a good model for understanding such processes as hypertension, irritable bowel, etc. Zhang et al in Dec 04 Brain Research have shown a role for Substance P in sleep. Is all sensation which monitors “negative” events, susceptible to hypersensitivity, as is pain? Could the “noxious” aspect of fatigue explain the tendency for brain damaged patients to sleep “too much” or for Central Pain patients to have sleep disturbance? Are their universals which result from proteins which change their shape and refuse to function in an acidic environment?

Putnam believes the role of pH sensitive (chemosensitive) cells will not be limited to one K+ channel, but will extend to many K(+) channels as well as Ca(2+) channels which are involved as targets of chemosensitive signals.

He believes the effects of acidity will be shown on extracellular pH, intracellular Ca(2+), gap junctions, oxidative stress, glial cells, bicarbonate, CO(2), and neurotransmitters. We add here that the effects of acidity will also be shown on protein folding, protein structure, protein shape, and configuration.

The role of acidifying chemicals is so pervasive in nerve injury pain that we hope the computing power necessary to describe changes in shape will soon be made available. The Stanford fils sharing system is currently the leader in protein folding studies. Given the extreme importance of shape in protein function, this is work which is long overdue and is foreshadowed by current work, such as that by Putnam.