Biochemistry of pain relief with intracerebral stimulation. Few facts and many hypotheses.

On the basis of data obtained from subprimates subjected to acute pain stimuli, it has been hypothesized that the suppression of chronic pain in man during stimulation in the periventricular region involves endogenous opioid mechanisms. However, there is at present no direct and unequivocal proof that the pain relief in man is necessarily and entirely dependent upon such mechanisms. There exist several putative substances with opiate-like properties but they are difficult to identify. The assay methods lack specificity and cross-reactions are common. There are only a few studies published on the influence of intracerebral stimulation in man on the CSF-content of opioid substances; the changes observed are inconsistent, and data are only given on patients having satisfactory pain relief. Furthermore, measurements have been made only during the course of a few hours and nothing is reported on the relationship between the changing concentrations of the substance and the level of pain. The observation that Naloxone may reverse the effect of intracerebral stimulation has become the keystone in postulating common mechanisms for stimulation-produced pain relief and morphine analgesia. The fact, that Naloxone is sometime ineffective or has to be used in huge, and unphysiological, doses is generally disregarded. There are a number of substances which may serve as neurotransmittors in pain transmission and pain inhibition but their mode of action in the generation and suppression of chronic pain is entirely unknown. Data collected from various European clinics covering more than 200 patients subjected to intracerebral stimulation show that the outcome of this treatment is highly unpredictable. Intracerebral stimulation as a clinically useful treatment of chronic pain can not be further developed unless hard data on its biochemical background in man are provided.