Theophylline increased sensitivity to nociceptive stimulation and regional turnover of rat brain 5-HT, noradrenaline and dopamine.

: Theophylline is able to decrease the thresholds of nociceptive stimulation (motor response, vocalisation and vocalisation afterdischarge), the effects being maximal at 30 minutes after administration. At this time theophylline was found to increase the endogenous level of dopamine in the telencephalic cortex and decrease the level of noradrenaline in regions including the diencephalon and the striatum. After inhibition of tyrosine hydroxylase with α-methyl-p-tyrosine, theophylline was found to decrease the depletion of dopamine brought about by the inhibitor in the telencephalic cortex, indicating a decreased turnover of dopamine in this region. Theophylline was able to accelerate the decrease in noradrenaline concentration in the diencephalon-striatum region induced by the enzyme inhibition, indicating an increased turnover of nordarenaline. The 5-HIAA content in the telencephalic cortex was found to be decreased by theophylline and increased in the mesencephalon-pons-medulla oblongata region. After pre-treatment with probenecid the latter increase was more pronounced while the decrease in the cortical structures was abolished by the pretreatment. It was furthermore found that probenecid per se was able to increase the thresholds for nociceptive stimulation and was able to counteract the effect of theophylline on these thresholds, and in preliminary experiments probenecid was found to affect the brain concentrations of noradrenaline. Inhibition of tyrosine hydroxylase was also found to counteract the decrease in the threshold of vocalisation afterdischarge produced by theophylline. From the experiments it seems possible that there is a relationship between a reduced turnover of dopamine and serotonin in the telencephalic cortex and the theophylline-induced decrease of the threshold for vocalisation afterdischarge (affective component of the pain reactions) while the modulation of the vocalisation response may be related to the serotonin metabolism in lower brain stem structures.

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