Without this Molecule, You Have No Memory

Another breakthrough in brain science which may explain loss of working memory in central pain.

This one was considered significant enough to make the major journal, Science.

Shema, et al at Science (2007) 317: 951-3 have determined that a blocker of PKMzeta can wipe out memory.

It was accepted as axiomatic that memory represented a wiring of sorts that memorized things so they could be recalled. There is probably some element of this, but it turns out that a protein kinase, PKMzeta, maintains memories. Without it, your long term memory is wiped out. You may recall that things are kept in short term memory, and then become long term memory.

Patients with central pain have been noted to have decreased working memory. The simplest test for working memory is counting backwards from 100. The normal patient can do this speedily. Someone with working memory impairment is slower than in going up from 1 to 100, because counting backwards requires the brain to calculate a subtracted sum, and then fix that sum in memory in order to perform the next calculation. This is a type of doing two things at once. Another test is called spontaneous alternation*, but is is bit more complicated and beyond the scope of this article.

Bogduk’s group has been the main authors on this aspect of central pain specifically. However, the information has not penetrated most of the pain clincs in the U.S. Consequently, many CP subjects have been hard pressed to make a case for it to their clinicians. Loss of working memory is sometimes defined as “distractability” but it is really more subtle than this. It has to do with the inability to do two things at once (eg. talk on the phone while someone else is talking to you in the background). Another aspect is less ability to concentrate, with decreased memory over the short term, as well as loss of long term memory. Central pain loss of working memory is not exactly like loss of working memory in certain other conditions. We are hoping the surveys will allow us to make some definitive statements about this.

The idea that pain chemicals could be associated with memory has always been hard to swallow, given the conventional idea about how memory works. No one suspected that a protein kinase maintained memories, just like worker bees maintain the hive.

An isoform of protein kinase C, (a well known pain chemical), which is known as protein kinase Mzeta, has been found to perform the perpetuation of long term memory. This is shocking because it was thought to be more a function of synapses and wiring than a chemical phenomena of such simple order.

This information may embolden you to speak of memory impairment as a consequence of alterations in your pain chemicals. Obviously it will be some time before this matter is studied in central pain. Still, it gives you a toehold, which is more than you have had in the past when trying to discuss this particular aspect of central pain.


Bingel et al 1: Neuron. 2007 Jul 5;55(1):157-67. Pain affects cognition. The modulatory unit affecting working memory is in the parietal cortex [probably the posterior parietal cortex, near the insular cortex--pain processing in SII is also located there].

Karp et al Pain Med. 2006 Sep-Oct;7(5):444-52. Pain decreases mental flexibility, as in number switching game.

Sarnthein et al Int J Psychophysiol. 2005 Aug;57(2):87-96. The thalamus is involved in working memory. When subjects activated their working memory by counting backwards, the local field potentials increased in the thalamux, as did theta waves measured at the scalp, as measured on electroencephalography (EEG).

Ellis et al Int J Neuropsychopharmacol. 2006 Apr;9(2):175-89. Muscarinic receptor antagonism with scopolamine resulted in deficits in working memory… Nicotinic antagonism with mecamylamine had no effect on any of the cognitive processes examined. Simultaneous antagonism of both muscarinic and nicotinic receptors with mecamylamine and scopolamine impaired all cognitive processes impaired by scopolamine and produced greater deficits than either muscarinic or nicotinic blockade alone, particularly on working memory, visual attention and psychomotor speed.

HIramatsu et al. Behav Brain Res. 2005 May 28;160(2): The chemical 374-81Be(-)-3-Acetyl-6beta-acetylthio-N-cyclopropylmethyl-normorphine induced improvement in scopolamine-induced impairment of *spontaneous alternation.

Dowman, Brain Topogr. 2004 Fall;17(1):3-12 Regarding somatosensory evoked potentials, the P2 wave is NOT a pain P3a variant. Rather it represents processing of pain in working memory.

Apkarian et al Pain. 2004 Mar;108(1-2):129- Chronic pain patients are impaired on an emotional decision-making task.

Houlihan Int J Psychophysiol. 2004 Jan;51(2):181-7. Pain affects an attention-switch mechanism.