ABSTRACT
The analgesic effects of the synthetic opiate fentanyl citrate (0.1 mg) on subjective pain reports (SPR) and late-wave event-related potentials (ERP) recorded during painful dental stimulation were examined in human subjects. Such waves have been shown to reflect the contribution of cognitive variables, such as expectancy and belief, to perception. In addition, the study was intended to demonstrate a dose-related narcotic antagonism with injection of naloxone (1.2 or 0.4 mg) or normal saline (double-blind) following IV fentanyl administration. Fentanyl reduced both ERP waveform amplitudes and SPR as have previously studied analgesic agents, such as nitrous oxide, acupuncture, and aspirin. Naloxone injection reversed both ERP and SPR changes, but surprisingly, a reversal of narcotic analgesia equal to that of 0.4 mg naloxone was seen with saline injection. By chance, all subjects were health-science students or professionals who were knowledgeable in opiate pharmacology, and so placebo reversal was hypothesized. Alternatively, it was hypothesized that fentanyl cleared more rapidly than predicted, thus, producing apparent reveal. In a second experiment involving similarly knowledgeable subjects with identical procedures and testing intervals, subjects received 0.1 mg fentanyl, but no reversal injection. The fentanyl effect was constant across this time period. The data, thus, support the hypothesis where the subjects were knowledgeable in opiate pharmacology, was placebo opiate antagonism.
Subject(s)
Analgesia , Narcotic Antagonists , Placebos , Tooth/physiology , Adult , Analysis of Variance , Dose-Response Relationship, Drug , Electric Stimulation , Electrophysiology , Humans , Male , Naloxone/pharmacologyABSTRACT
Vertex evoked potentials (40--500 ms) elicited by painful dental stimulation were compared with those elicited by innocuous auditory stimuli across three rates of stimulus repetition: one second, four seconds, and eight seconds. In both modalities peak amplitude of the major waveform components increased linearly over log rate as stimulus repetition was slowed, and latency of the latest positive component was increased. No changes in subjective stimulus intensity across rate of repetition were reported. These observations demonstrate that the normally close relationship between subjective pain report and EP amplitude is not variant, and they suggest that the development of EP methodology in human pain research should proceed conservatively.
Subject(s)
Auditory Perception/physiology , Cerebral Cortex/physiology , Dental Pulp/innervation , Nociceptors/physiology , Adult , Electric Stimulation , Evoked Potentials , Humans , MaleABSTRACT
Four experiments were conducted to examine the individual and combined effects of pargyline and tryptophan on the duration of tonic immobility in chickens. Injection of either compound alone produced a dose-dependent potentiation of tonic immobility. However, combined administration of pargyline and tryptophan resulted in a dramatic attenuation of the response and this effect was completely blocked by pretreatment with p-chlorophenylalanine. In addition to reducing the duration of tonic immobility, combined administration of pargyline and tryptophan produced a complex behavioral syndrome which may be analogous to that observed in mammals after similar drug treatment. These results suggest the need for a modification of the recently proposed serotonergic-raphe model of tonic immobility.
Subject(s)
Motor Activity/drug effects , Pargyline/pharmacology , Tryptophan/pharmacology , Animals , Chickens , Dose-Response Relationship, Drug , Drug Interactions , Fenclonine/pharmacology , Restraint, PhysicalABSTRACT
Consistent with a serotonergic-midbrain raphe model of tonic immobility, four experiments designed to affect changes in serum tryptophan produced reliable effects on the duration of the response in chickens. Systemic injections of tryptophan, the dietary precursor to serotonin, led to a dose-dependent increase in immobility, with optimal effects being observed within 30 min after injection. Dietary depletion of endogenous tryptophan served to attenuate the duration of immobility, and a diet completely free of tryptophan, but supplemented with niacin, practically abolished the reaction. Dietary replacement served to reinstate the response. In a fifth experiment, tryptamine, an alternative metabolic by-product of tryptophan, was found to have no effect on immobility. The data are discussed in light of evidence showing serotonergic involvement in tonic immobility.
