Posted by franco neuro on May 13, 2005, at 22:46:42
In reply to Desipramine in neuropathic pain » franco neuro, posted by ed_uk on May 13, 2005, at 11:35:49
Yes, I like the fact that it's not particularly anticholinergic. I want to dull the pain, not my intellect. I'm really trying to get at the heart of how this all happened. No one has explained it better that Jay Goldstein in "Tuning the Brain". I read that book and it was as though he was describing my life. Here are some excerpts:
"If an individual is temperamentally, developmentally, and/or environmentally predisposed to interpret too many stimuli as possibly threatening, then attentional resources, which require increased secretion of neurotransmitters norepinephrine (NE) and dopamine (DA) (among others), will be consumed locally at too rapid a rate, and the brain will develop a deficit in them sooner or later. Then, an overt neurosomatic disorder will occur."
"It has taken me twenty years of thinking to succinctly synthesize what is described here, i.e., improper selection of salience produces overuse of the 'attentional spotlight,' which raises signal-to-noise ratio by overly frequent secretion of dopamine and norepinephrine. At some time during a person's life, a neural network orchestrated by the prefrontal cortex may be unable to induce sufficient production of these transmitter substances. This inability may be sporadic or virtually constant, but the result will be neurosomatic symptoms."
"A postulate to which I shall continually refer in this book is that patients with neurosomatic disorders have overly learned and overly generalized associative responses and that the primary molecular basis of this memory dysfunction involves the NMDA receptor."
Me again. Basically, an oversensitized NMDA receptor for glutamate and/or an over secretion of glutamate causes the brain to be in a state of overexcitability or hypervigilance (i.e. overactive fight or flight response, increased startle response, anxiety, poor response to stress, perceiving non-threatening situations as threatening, etc., etc.) This state of perpetually being stressed out ultimately leads to a depletion of DA and NE.
"Inhibiting the NMDA receptor, the presynaptic release of glutamate, and facilitating NE and DA secretion should be effective ways of treating neurosomatic disorders."
That's it in a nutshell. The man is a genius. I love this book. He has a whole list of his favorite medications. But what he considered the best treatments and also the best tools for predicting which medications would work best for his patients, are IV ketamine (NMDA antagonist) and IV lidocaine (primarily suppresses glutamate release). Now all of this makes perfect sense to me. But I can't seem to find a doctor who knows his *ss from his elbow, let alone what the function of the NMDA receptor is!
poster:franco neuro
thread:473033
URL: http://www.dr-bob.org/babble/20050510/msgs/497565.html