Controlled Test of the Analgesic and Relaxant Properties of Nitrous Oxide

Transcription

1 Reprinted from the JOURNAL OF DENTAL RESEARCH, Vol. 53, No. 2, Pages: g American Dental Association, All Rights Reserved. Controlled Test of the Analgesic and Relaxant Properties of Nitrous Oxide VERNON DEVINE,* RICHARD ADELSON, JOEL GOLDSTEIN, STUART VALINS, and GERALD C. DAVISON Slate University of New York at Stony Brook, Stony Brook, New York 11790, USA The pain reducing and calming properties of nitrous oxide mixed with oxygen were evaluated with the use of placebo and standard control groups. Subjects under nitrous oxide had higher pain thresholds and a higher tolerance for shock than placebo and control subjects. They also reported themselves as more relaxed than did placebo and control subjects. Nitrous oxide combined with oxygen has been described as an effective analgesic and relaxant in dentistry.) its routine use in dentistry is limited, however, because of several :actors. Historically, nitrous oxide was used is an anesthetic; in the high doses necessary For such application, patients typically pro-g r ess through an excitement phase that is unpleasant for the patient and difficult for the professional to manage. However, as innovators such as Langa 1 have documented, clinical experience indicates that judicious use of this drug as an analgesic and relaxant can he useful to the dentist in working with the fearful dental patient and in making the dental experience for the normal patient relatively painless and even pleasant. What seem to be totally lacking in the literature are reports of controlled studies in which the analgesic and calming properties of lower doses of nitrous oxide mixed with oxygen arc evaluated carefully in controlled designs. This lack of studies leaves open the possibility that patient and dentist expectation play a major role in the clinical findings. The history of the placebo eflect 2 document: This research was supported by the National Institute of Mental Health, National Institutes of Health, Bethesda, Md. Received for publication September 18, Present address: Department of Psychology, University of Minnesota, Minneapolis, Minn the important role that is played in changing behavior, even unwittingly, by attitude and expectations of both patient and dentist. This paper presents the results of a study that was designed to deal with these issues by objective assessment of the pain-reducing and calming properties of nitrous oxide in a design that permitted evaluation of any placebo response that might exist in its use. The initial part of this study assigned subjects to three conditions: drug (nitrous oxide and oxygen); placebo (oxygen only); and control (no mention of drugs). All subjects were given a standard series of shocks of increasing amperage. We hypothesized that subjects under nitrous oxide would report that a shock was painful at a higher amperage than subjects in the placebo and control groups, and that subjects under nitrous oxide would take shocks of higher amperage before reporting that they could take no more. It also was hypothesized that subjects under nitrous oxide would report that they were more relaxed than placebo or control subjects. To assess the effects of suggestion, a placebo condition was devised in which subjects received a dosage of nitrous oxide and oxygen that resulted in the report of feeling a drug effect, after which the nitrous oxide was surreptitiously turned off; therefore, tests for pain and tolerance took place while subjects breathed only oxygen. Our intention with this procedure was to instill in placebo subjects the belief that they were in fact breathing nitrous oxide; if such subjects behaved no differently from subjects who did not receive the drug, yet behaved differently from subjects who received nitrous oxide, the evidence would suggest that nitrous oxide had a specific effect greater than that of the placebo. 486

2 Vol 53 No. 2 NITROUS OXIDE TESTS 487 Materials and Methods The participants were 54 undergraduates enrolled in an introductory psychology course at a large university who signed up for an experiment entitled "the interpretation of stimuli." They were given one hour of credit toward a three-hour experimental participation requirement of the course. There were three experimenters; two were dentists and one was a psychologist. One dentist was present for each drug and placebo subject but was not present for subjects in the control group. For the control condition, no mention of drugs was made. The psychologist. merely informed control subjects that the experiment was being done to test subjects for thresholds of electric stimulation. The actual shock series was run identically to that of the other groups. For the placebo and drug groups, the psychologist greeted each subject and explained that the experiment was being done to investigate the effect nitrous oxide has on interpretation of stimuli. "The subject was told that his sensitivity to electric stimulation would be determined by means of a specially const r ucted apparatus that was capable of administering electric shocks of various intensities. The subject first was given shocks below his threshold for sensation; these shocks were raised gradually in small increments. The subject was told to report when he first perceived the shock, when he first felt that it was "painful or unpleasant," and when he perceived the shock to be so painful or unpleasant that he couldn't tolerate it any more. Brass, silver-plated, cuptype electrodes, 5/16 inch in diameter, were taped (using electrode paste) to the first and third fingers of the nondominant hand. The shock generator delivered 60-cycle shocks, 500 msec in duration. The shock intensities began with 0 ma and was increased by 0m a at each step. Before each shock the subject was told: "Here comes the stimulus." After a delay of ten seconds, the next shock was announced in the same manner. The psychologist recorded the intensity of the shock after which the subject reported sensation, pain, and tolerance. While the subject filled out a health checklist, the psychologist summoned the dentist, and after he introduced the dentist, he left the room. The dentist then explained the use of nitrous oxide as he customarily did in his dental practice. He emphasized that it would make the subject feel comfortable and relaxed, but made no mention of its effects on pain perception. After he fitted the gas mask on the subject's face, the dentist administered a mixture that both dentists used routinely in their practice, that is, 3 liters oxygen per minute and 2 liters nitrous oxide per minute; this was done with a Foregger analgesia apparatus. a The subject sat in a reclining lounge chair with his eyes closed, and was told to inform the dentist as soon as he began to feel differently, especially when he felt sensations such as tingling in his arms and legs. Only after the subject began to breathe the mixture did the dentist turn over a file card that indicated whether this was to he a placebo or drug subject. When the subject reported that he felt differently (usually within three minutes), the dentist told him he was adjusting the dosage to that required for the experiment. For drug subjects, he actually left the dials where they were. For placebo subjects. he turned the nitrous oxide off, leaving the oxygen on. After three more minutes, the dentist summoned the psychologist to begin the shock series. This procedure for a placebo condition was adopted to ensure that subjects believed that they were getting a drug (that is, subjects actually "felt" something happen). This was necessary because of the sophistication of the subjects, most of whom were in their second semester of introductory psychology and had learned about placebo research in the course and had participated in other experiments, many of which involved deception. The procedure was highly effective; no placebo subjects reported that they did not believe the manipulation. included in this group were two subjects who had nitrous oxide previously in a dentist's office. To summarize the experimental conditions so far, the drug and placebo subjects were treated identically, with the exception that the nitrous oxide was turned off for the placebo subjects; thus, both groups thought they were receiving a drug and that the experiment was concerned with the effects of this drug on their interpretation of shock stimuli. No mention of drugs was made to the control subjects, and they believed that the experiment was concerned solely with the determination of their thresholds for. Foregger Co., Allentown, 1'a.

3 488 DEVINE ET AL J Dent Res March April 1974 electric stimulation. They received the same instructions for the shock series as described for the drug and placebo subjects)) The shock series actually began with 0 ma, and each shock increased at the rate of 0 ma for each trial. Duration was 0.5 seconds. The subject reported when he could first feel the stimulus, when it first became painful, and when he could no longer take any more. He also was asked to rare the terminal shock on a 0 to 0 scale of painfulness, with 0 as no pain; 25, slight pain: 50, painful; 75, very painful; and 0. most painful of anything experienced. After this rating, the subject rated his degree of relaxation on a 0 to 0 scale as follows: 0, not relaxed; 25 slightly relaxed: 50, relaxed; 75, very relaxed; and 0, most relaxed ever been. Results The series trial number (disregarding the first trial on which no shock was given) on which the subject first reported feeling the stimulus, first reported pain, and asked to stop the series (tolerance), combined with the ratings on painfulness of last stimulus and degree of relaxation, are the data for this study. A one-way analysis of variance was used to test for significant differences between groups. SENSATION THRESTOLD. The three groups > did not differ significantly (F = 2.18; P 0.) in sensation threshold, although means were in the expected direction (Table 1). It is possible that a shock series in which smaller increments were used from trial to trial would show a significant difference; this study was hampered by the fact that 76% of all subjects reported feeling the second shock, with a range of only one to four. PAIN THRESHOLD. The three groups differed significantly in regard to pain threshold (F = 8.01: P < 0.01). The three groups were compared with each other by Duncan's b Preliminary tests indicated that the psychologist could not differentiate drug from placebo subjects at better than a chance level during the shock series. Hence, he was essentially blind regarding the subject's condition when comparisons were made between placebo and drug groups, although not when comparing control subjects and other groups (control subjects did not wear the mask at any time). The procedure also made it possible for the dentist to prepare the subject without knowing which subjects were actually going to have the drug during the shock series. This ensured that there would he no systematic differences between drug and placebo groups in preparation for the drug by the dentist, thus eliminating another possible source of experimenter bias., TABLE 1 MEAN SHOCK TRIALS BEFORE SUBJECTS REPORTED FEELING SHOCK Trials Control Placebo Drug multiple-range test, a test that allows assessment of the significance of differences between groups after an overall significant difference has been found by an analysis of variance. These comparisons showed that both placebo and control groups were significantly inferior to the drug group (P < 0.01) but were not significantly different from each other (Table 2). TOLERANCE THRESHOLD.The three groups TABLE 2 MEAN NUMBER OF SHOCKS BEFORE SUBJECTS REPORTED PAIN Shocks Control Placebo Drug

4 Vol 53 No. 2 NITROUS OXIDE TESTS 489 TABLE 3 MEAN NUMBER OF SHOCKS RECEIVED BY SUBJECTS BEFORE TERMINATING THE SERIFS Shocks Control Placebo Drug differed significantly in tolerance threshold (F = 5.69; P < 0.01). Again, comparisons by use of Duncan's multiple-range test indicated that control and placebo groups were significantly inferior to the drug group (P < 0.05), but were no different from each other (Table 3). PAINFULNESS OF LAST SHOCK. The painfulness rating of the last shock did not differ significantly among the three groups (F = 1.8; P > 0.). This result indicates that TABLE 4 SUBJECTS ' MEAN RATING OF PAINFULNESS OF TERMINAL SHOCK (0 to 0 scale) Scale Control Placebo Drug TABLE 5 SUBJECTS ' MEAN RATING OF RELAXATION AT END OF SHOCK SERIES (0 to 1 00 scale) Scale Control Placebo Drug nitrous oxide subjects rated their last shock no more painful than placebo or control subjects did, despite the fact that the nitrous oxide subjects were rating shocks of much larger magnitude (Table 4). RELAXATION RATING. The three groups differed significantly in their self-report of relaxation at the end of the shock series (F = 9.40; P < 0.01). The data indicate a progression in reported relaxation from control through placebo to drug group (Table 5). The Duncan test showed that control and placebo groups were significantly less relaxed than the drug group, but the difference between the control and placebo groups reached only marginal significance (P < 0.). Discussion Nitrous oxide, when mixed with oxygen, clearly influences a person to perceive a painful stimulus as being less painful. It also induces a relaxation effect greater than a placebo condition. By measuring the perception of pain in two ways, one hypothesis about the effects of nitrous oxide was tested and not supported. It has been suggested that nitrous oxide influences a person's willingness to endure pain without influencing the perception of pain. One might report, "Yes, it's hurting but I don't care." By asking subjects to report when the shock was first painful and by seeing how much amperage the subject was willing to endure, we attempted to separate willingness to endure pain from the perception of pain. However, both measures yielded significant differences. The "I don't

5 49 0 DEVINE ET AL J Dent Res March-April 1974 care" hypothesis also would predict that nitrous oxide subjects would report the terminal shock as more painful than the other two groups. However, the self-reported painfulness measure of the terminal shock showed no significant differences among groups. Conclusions These results suggest that nitrous oxide combined with oxygen reduces the perception of pain. Also, an increase in subjective feelings of relaxation while under the influence of the drug is indicated. Thus, nitrous oxide may he useful in dentistry for two reasons. First, it should reduce the occasional or even frequent pain or discomfort invol v ed in dental work (for example, the pain or discomfort involved in injection of an anesthetic or having the mouth open in an uncomfortable position). Secondly, the sensation of relaxation that nitrous oxide produces should reduce the anxiety that patients frequently report to he associated with the dental situation; thereby, it might improve general manageability. This combination of effects should make the dental situation more pleasant for patients who are highly anxious in the dental situation or who complain about the minor irritations that accompany dental work. References 1. LANGA, H.: Relative Analgesia in Dental Practices Inhalation Analgesia with Nitrous Oxide, Philadelphia: W. B. Saunders & Co., SHAPIRO, A.K.: A Contribution to the History of the Placebo Effect, Behav Sci 5: 9-135, ROSENTHAL, R.: Experimenter Effects in Behavioral Research, New York: Appleton-Century-Crofts, 1966.