426 Brain Research, 215 (1981) 426~29 ~) Elsevier/North-Holland Biomedical Press The influence of naloxone on dental pain threshold elevation produced by peripheral conditioning stimulation at high frequency ANTTI PERTOVAARA and PENTTI KEMPPAINEN Department of Physiology, University of Helsinki, Siltavuorenpenger 20 J, SF-O0170 Helsinki 17 (Finland) (Accepted February 19th, 1981) Key words: dental pain -- naloxone -- stimulation-produced analgesia -- transcutaneous nerve stimulation The phasic dental pain threshold elevation produced by high-frequency transcutaneous electrical nerve stimulation (TENS) in healthy humans was not abolished by naloxone. A prolonged (20 min) high-frequency TENS did not cause any tonic pain threshold elevation. The results indicate that opioid-dependent systems have only a minor if any contribution to alleviation of experimental pain during high-frequency TENS. Pain alleviation induced by transcutaneous electrical nerve stimulation (TENS) at high frequency (10-100 Hz) has proved effective in many clinical studies. However, the mechanism causing this effect is still a matter of debate. Many investigators have suggested that activation of afferent inhibition at spinal or even more central levels of the nervous system is the major factor (cf. ref. 1). Concomitantly, a recent experimen- tal study with rats suggested that opioid-dependent pathways at both spinal and supraspinal levels contribute to pain threshold elevation during high-frequency TENS 14. On the contrary, some studies have suggested that a peripheral electrogenic blockade or fatigue of pain mediating primary afferents may explain the pain relief or at least part of it 4,5,8. Moreover, in clinical studies with human patients opioid- dependent systems seem to have only a minor role in pain alleviation induced by high- frequency TENS 11. The purpose of the present study was to find out if the phasic dental pain threshold elevation found previously in experimental conditions with humans could be abolished by naloxone (a specific narcotic antagonist) 3. Moreover, it was intended to find out if high-frequency TENS of long duration causes not only a phasic but also a tonic dental pain threshold elevation indicating activation of similar mechanisms as during acupuncture or during low-frequency TENS2,L Six trained, unpaid volunteers (age range 23-37 years, all males) were tested. The experiment was fully explained to each subject and a written consent form signed. TENS was applied from a conventional portable stimulator (EMSET-stimulator, Nissen, Helsinki) which produced biphasic impulses (Fig. 1) at a frequency of 100 Hz. Standard carbon rubber electrodes (20 sq. cm), coated with electrode gel, were firmly