Neramexane makes an appearance

An antagonist of NMDA receptors and a potassium channel blocker make an appearance in Germany.

Klein, et al, writing in Eur J Pain. 2007 Apr 19 report that neramexane, which blocks the N-methyl-d-aspartate (NMDA) receptor shows effectiveness against neuropathic pain.

There is a problem with the report. The authors do not fully differentiate between central pain, central sensitization, and pain from peripheral nerve injury. However, the principle still holds. Blockade of the NMDA receptor helps pain. We are curious about side effects and if this drug moves further along, there will undoubtedly be more on that. NMDA also drives memory.

The authors also make mention of a potassium channel blocker flupirtine in the intradermal capsaicin injection model.

The authors state:

“Pain evoked by intradermal capsaicin injection as well as pain evoked by pinpricks was significantly reduced by neramexane (-22% to -30% vs. placebo) in the non-sensitized skin indicating a marked analgesic effect. Moreover, dynamic mechanical allodynia (pain to light touch) was also significantly attenuated by neramexane (-28% vs. placebo). However, static secondary hyperalgesia to pinprick stimuli after capsaicin injection was not significantly reduced (-9% vs. placebo).”

There are two ways to look at this data. One is to say central pain is so severe (at least the evoked variety is) that a 22% decrease from hell pretty much still leaves you in hell–why can’t they do better than 22%. Secondly, was the decrease accurately measured?

Then, there is the analytic approach which says, “Since evoked CP is so terribly severe, even a modest 22% decrease would be appreciated.” The question is whether 22% would be sufficient to make the person functional. If the burning were 22% less would that allow patients to wear shoes, for example. We think not. Twenty two percent reduction is about what you get if you can keep stress completely (or mostly) out of life. The pain will always create its own stress so we are speaking about adrenaline raising stress of other varieties.

Those with really terrible central pain are in agony and would still be in agony down twenty two percent later. For moderate cases, they probably struggle along. If the study had differentiated spontaneous from evoked pain adequately, then maybe we would know what to expect.

Frankly, we were sort of hoping for a 100% reduction in pain.

Notice that this drug strongly suggests a difference in the way the body perceives static, unmoving touch and that which might involve a tiny degree of friction or motion (dynamic) touch. There is no explanation in existing anatomic theory for this finding.

Flupirtane, the potassium blocker, didn’t make the grade. It was not effective.

In case you don’t know it, the Germans are the leading pharmaceutical manufacturing country in the world. It is good to see they are interested in neuropathic pain. If the U.S. has anything to offer, it is that we are hopefully a little further along in discriminating among the various types of neuropathic pain. The Canadian, American and British literature have been a little better in sorting out anterior cord pain, posterior cord pain, visceral pain, evoked pain, and spontaneous pain.’The legacy for this is owed to S. Weir Mitchell who was making distinctions clear back at the time of the Civil War.

Radiologists around the world are attempting to image pain, but until they understand the VARIETIES, they may not be able to make sense of their data.

Another way to approach the differentiation is to observe the effects of drugs on the various pains. Of course, this approach also risks giving such drugs to EVERYONE with neuropathic pain, with benefit perhaps only going to a few.

Nevertheless, we are grateful for any progress, and this new German article represents progress in the study of drugs for treating neuropathic pain. We are especially impressed that the authors differentiated between an analgesic effect and an anti-hyperalgesic effect. It is not common for scientists to credit the possible differences between pain and hypersensitization pain. These researchers did so credit.

The profit motive will drive research into pain of peripherhal origin which will hopefully spill over into something which can be used against CENTRAL pain.