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Addicrrve Bthavrors. Vo1. 9. pp. 211-225, 1984 0306-t603/84 S3.00 +.00 Prtnted tn the USA. All rights reserved. Copyright = 1984 Pergamon Press Ltd I a I I I I I I I I I I I I BRIEF REPORT SUBJECTIVE RESPONSE TO CIGARETTE SMOKING FOLLOWING AIRWAY ANESTHETIZATION J.E. ROSE The Neuropsychlatric Institute, University of California and V.A. Medical Center, West Los Angeles M.C. ZINSER V.A. Medical Center. West Los Antdes D.P. TASHKIN, R. NEWCOMB, and A. ERTLE School of Medicine, University of California Absttwct-Subjeaive response to cigarette smoking was assessed after partial blockade.of upper and lower airway sensations by the topical appiication of lidocaine. Pack-a-day smokers were yven one cigarette after each of four conditions: (1) mouth anesthesia, obtained by rins- ing the mouth with 2% lidocaine; (2) mouth and pharyngeal anesthesia. in which subjects rinsed their mouths and gargled with 2% lidocaine; (3) upper and lower airway anesthesia, in which subjects nnsed their mouths and gargled with a 2!% lidocaine solution, and inhaled a mist con- taininj 4% lidocaine (60 breaths): and (4) saline control, in which all solutions (rinse, targle and inhalation) were saline. A significant linear decline in cigarette craving occurred with in- creasing anesthesir, and desirability ratings over the first several puffs were also reduced by anesthesia,~These rssnlu su&eu that sertsory cues are important factors in smokinj satisfae- tion`.}utd their influence can be analyzed with the use of local anesthetia. Sensory factors in cigarette smoking have received relatively little investigation despite their potential motivational significance (Stepney, 1981). Smokers often report enjoy- ing the taste of cigarettes (Zagona & Zurcher, 1965), and taste stimuli are known to generate powerful preferences and aversions (Garcia, Hankins, & Coil, 1977). However, the study of these perceptual aspects of smoking has been largely over- shadowed by investigations into the pharmacologic actions of nicotine and behav- ioral regulation of nicotine intake by smokers (Gritz, 1980; McMorrow & Foxx, 1983). To the extent that smoking is a pharmacologic habit, equivalent to nicotine self- administration, selectively removing the sensory qualities of smoke should not have a profound impact on the desire to light a cigarette. Conversely, if the perceptual effects of smoke are important reinforcing stimuli, then eliminating them should substantially affect the enjoyment of smoking. We conducted the present experiment to determine whether the blockade of taste and related stimuli by a short-acting topical anesthetic would affect cigarette craving and smoking satisfaction. Additionally, we hoped to establish whether critical sensations could be localized in the mouth, pharynx or trachea in order to evaluate the sugiestion by Cain (1980) that pharyngeal and tracheal stimulation via the common chemical sense pathways (which convey pungency, warmth and pain), is a more important determinant of the sensory qualities of cigarette smoke than are the classic taste sensations of sweet, salty, sour and bitter. Our strategy i This research was supported in part by USPHS Grant No. DA 02663 from the National Inuitute on Drug w Abuse and by the Medical Research Service of the Veterans Administration. Requests for reprinu should be sent to Jed E. Rose. Veterans Administration Medial Center West Los Angeles. Brentwood Division (691/B151D), Los Angeles, CA 90073. ~ ~ 211 ~ CT ~ ° ~ ~ . a 0

I I I I I I I I I I I I I I I 212 J.E. ROSE et alL was to administer the local anesthesia using the procedures of mouth rinsing, gargling and inhalation in order to restrict the anesthesia to selected areas. SUBJECTS Subjects were screened to include only those smoking a pack a day or more of a cigarette brand delivering (FI'C) at least 0.7 mg nicotine, and to exclude anyone with cardiovascular or lung disease, asthma or known allergy to local anesthetics. Eighteen subjects participated in the study (7 females, 11 males). Their average age was 31 yrs, (SD = 7.2) and they smoked an average of 24 cigarettes per day (SD = 6.4), with a mean nicotine delivery of 1.0 mg (SD -.24). PROCEDURE The experimental session consisted of four periods presenting each of fo'ur anesthesia treatments. After each anesthesia condition subjects smoked one cigarette of their own brand. In each condition, subjects were asked to rinse their mouths three times for 90 sec each time with either lidocaine (2e/i) or saline. Mouth rinsing was followed immediately by gargling three times with a second solution (2010 lidocaine or saline). Over a subsequent (or preceding) 10 min period subjects inhaled 60 breaths from a nebulizer that delivered a mist containing either 4°1o lidocaine or saline. The lidocaine aerosol was generated by adding 4 cc 4474 lidocaine solution to a flow-through nebulizer (DeVilbiss, Model 646) attached to a compressor-driver aerosol generator (Pulmo-Aide DeVilbiss, 561 series; Somerset, PA 15501) operated at 30 PSI with a jet air flow of 20.9 Vrnin and an estimated median droplet diameter of 2.8 micron (Mercer, Tillery, & Chow, 1968). Subjects inhaled the aerosol by inspiring slowly from functional residual capacity to near total lung capacity with a breath-holding time of 2-3 seconds. For half of the subjects the inhalations followed the mouth rinse and gargle, whereas for the remaining subjects this order was reversed (results did not differ between these groups, so data were pooled in the analyses). The four anesthesia condi- tions comprised the following: (1) Saline control: in this condition the rinse, gargle, and inhalation were all saline; (2) Mouth anesthesia: for this condition subjects rinsed their mouths with the lidocaine solution; the gargle and inhalation solutions were saline; (3) Mouth and pharyrrgeal anesthesia: the rinse and gargle solutions contained lidocaine, whereas the inhalation mist was saline: (4) Mouth, pharyngeal and tracheo- brortchial anesthesia: all solutions contained lidocaine in this condition. The procedure for the four conditions was identical except for the nature of the solutions used (lido- caine vs. saline control). In a separate study involving eight additional subjects, we determined the intensity and duration of mouth, oropharyngeal and tracheo-bronchial anesthesia produced during the above conditions by measuring the threshold for tasting sucrose, subjectively grading the strength of the gag reflex, and determining the threshold concentration of a citric acid aerosol solution eliciting cough, respectively. Subjects also rated the degree of numbness in the mouth and throat on a 10 point scale. Immediately following the rinse, gargle and inhalation of lidocaine, substantial numbness was reported for the mouth and pharynx (average rating of 9.5 and 7.4, respectively), the threshold for detecting sweetness was more than doubled, the gag reflex was blunted by roughly 60e/o and the threshold for eliciting the cough reflex was increased more than twofold. In general, local anesthesia of the upper respiratory tract was found to dissipate within 15-30 min, so the interval between the end of one anesthesia condition and the begi t- ning of the next was controlled to be approximately 30 minutes. ~ ~ ~ O ~ O ~

r I I I I I I I I I Immediately before and after smoking each cigarette subjects rated their craving to smoke, and during each cigarette subjects rated each puff for strength, harshness and desirability, using 10-point scales. The change in •end-expired carbon monoxide (CO) after smoking was determined from samples of exhaled alveolar air obtained after 20 sec of breath-holding and exhalation of the initial 500 cc of the expirate to eliminate dead space air from the sample. CO was measured using an electrochemical analyzer (Ecolyzer, Model Al. Subjects were run in groups of three to five, and the order of the four anesthesia con- ditions was counterbalanced across subjects. RESULTS The mean ratings of puff strength, harshness and desirability, as well as precraving (craving before each cigarette) and change in craving (craving after each cigarette minus precraving) were assessed for possible effects of the anesthesia. Each of these five variables was analyzed in a one-way repeated measures ANOVA (BMDP P2V), partitioned into orthogonal components. Cigarette craving (before smoking) was significantly affected by the preceding anesthesia condition: F0,51) a 3.38, p < .03; Ft1,17)lin = 8.88, p < .01. Figure 1 shows the linear decline in cigarette craving with increasing anesthesia. Interestingly, the reduction in craving associated with upper and lower airway anesthesia (craving in Smokina after airway anestheuuuon 213 8-1 BEFORE SMOKING I I I I I I 2 W ,,-0°___ ° AFTER SMOKING~ SAI,INE MOIJTM MOUTM MOl1TM CONTRM RINSE RINSE RINSE + + GARCLE GARGI.E t INMALATION ANESTHES{A CONDITIONS Fig. 1. Mean reported cigarette craving before and after smoking in each of the four ex- perimental conditions. C:7 ~A. ~ ~

I I I I I I 1 I I I I I I I I I 214 J.E. ROSE et al. condition I minus craving in condition 4) was highly correlated (r = .78, p < .01) with the degree to which subjects reported smoking in social situations. The change in craving following each cigarette was also diminished by anesthesia; t(3,51) = 4.20, p<.01; f1;1,17)lin = 10.05, p < .01. However, this drop in craving was negatively correlated with the initial precraving value, and covariance analysis failed to reveal a significant difference in post-smoking craving between conditions when pre- craving was partialled out t(3,S1) : 1.62, p > .1. Average ratings of puff strength did not differ between conditions: F(3,S1) - .74, p>.S. Nor were harshness or desirability ratings affected by anesthesia: F0,S1) : 1.13, p>.3 for harshness; R3,S1) :.S9 p>.S for desirability. However, a strong trend was noted in the desirability ratings across puffs: Ft4,S6) = 6.11, p < .001 when the mean rating for each block of puffs (divided into fifths) was analyzed. There was also a significant anesthesia condition x puff interac- tion: P712,18) = 2.66, p<.01; desirability was initially lower in the active anesthesia conditions, but the difference vanished by the end of the smoking periods. Two indices of smoking behavior were also measured to evaluate the possibility of significant differences in smoking topography between conditions: number of puffs taken from each cigarette (estimated from the number of puff ratings), and increase in expired air carbon monoxide after smoking. Neither of these measures was significantly different after anesthesia: F(3,51) = .85, p > .4 for number of puffs; F(3,51) : 1.45, p>.2 for CO increase. DISCUSSION Contrary to the predictions of a strict pharmacologic hypothesis, partial blockade of the sensory input from tobacco smoke had a dramatic effect on self-reported cigarette craving. The graded reduction in craving with increasing sensory blockade of the pharnx and trachea argues for the importance of sensations other than taste, support- ing Cain's (1980) hypothesis. Since blood lidocaine concentrations were not measured, we cannot exclude the possibility that central nervous system effects of systemically absorbed lidocaine could have directly influenced cigarette craving. This possibility seems unlikely in that local anesthesia induced by the topical administration of lidocaine was more salient than any CNS effects. Furthermore, the central effects of lidocaine would be expected to resem- ble those of cocaine, which increases cigarette smoking (R.K. Siegel, personal com- munication, 1983). It also seems unlikely that the reduction in craving produced by lidocaine was due solely to a nonspecific suppression of behavior by the novelty of the anesthesia or anxiety about the procedure, since smokers consume cigarettes in a variety of situations, and to an even greater extent under anxiety-provoking or stressful condi- tions, (Ikard, Green, & Horn, 1969). It is somewhat puzzling that subjective ratings of strength and harshness during smoking were not affected by the anesthesia, and several interesting explanations may be considered for this negative result. First, the subjects were aware that they were smoking their customary brand of cigarette throughout the session, and hence may have been biased in their ratings. However, this possibility has been discounted by a second study in which puffs were presented in random sequences from different strength brands that were visually disguised. Subjects were able to discriminate high from low nicotine puffs equally well when anesthetized as when receiving a placebo. A second explanation is that subjects compensated behaviorally for the anesthesia by tak- ing bigger puffs or inhaling more deeply, thus producing the same sensory impact, but I

I I I I I I I I I I I Smoking after airway anesthetization 215 requiring a stronger physical stimulus (more smoke) to do so. Puff volume was not measured directly, so that it is not possible to ascertain whether any compensatory changes occurred. Controlling puff volume and inhalation depth with spirometry or other means will be necessary to more fully evaluate this possible explanation. A third explanation is that subjects perceived the strength of the smoke by the immediate cen- tral nervous system impact of each "bolus" (Russell & Feyerabend, 1978). This explana- tion merits rigorous testing'but is unlikely to account for the lack of effect of anesthesia on harshness ratings, since the latter explicitly referred to a local irritating property of the smoke. A more plausible explanation is suggested by the fact that even in the most extensive anesthesia condition, subjects reported that they still felt the smoke deep in the chest. This small region of unanesthetized tissue may have been sufficient for accurate discrimination of strength and harshness. When an individual is hot, for instance, it may be possible to discriminate the temperature of the water in a swimming pool equally well by touching it with only a finger as by touching it with the whole body; however, the enjoyment would be expected to be much greater in the latter case. Analogously, the ability to discriminate strength and harshness of cigarette smoke may remain intact if only a small region of sensitive tissue remains unanesthetized; however, the enjoy- ment of smoking and desire to smoke probably depend upon sensations arising from several areas. The results of the present study may have important clinical implications which merit further exploration. Blockade of reinforcing sensory aspects of smoking is superficially similar to the blockade of the reinforcing effects of heroin with the opiate receptor antagonist naloxone, which has been shown to significantly reduce craving for heroin in opiate addicts (Judson, Carney, & Goldstein, 1981). Although we did not block the central effects of nicotine and only a portion of the sensory effects of the smoke were eliminated, the blunting of sensory feedback was sufficient to reduce craving. Our results raise new possibilities for smoking cessation strategies and demonstrate that local anesthetics can be useful tools for evaluating the relative importance of sensory vs. pharmacologic factors in smoking motivation. , REFERENCES Cain, W.S. Sensory attributes of cigarette smoking. In G.B. Gori t F.G. Bock (Eds.). Banbury Repcrtl: A safe crjantte? New York: Cold Sprinj Harbor Laboratory, 1980. Garcia, J., Hankins, w.G., 6 Coil, J.D. Koalas, men, and other conditioned gastronomes. In N.W.  Milgram, L. Krattter. Jt T.M. Allowa (Eds.). Food aversion /eornrnj. New York: Plenum Preu, 1977. !- Gritz, E.R. Smoking behavior and tobacco abuse. !n N.K. Mello (Ed.), Advances in substance abuse, V. 1. Greenwich. CT: JAI Press, 19i0. lkard, F.F., Green, D.E., t Horn. O.A. acale to differentiate between types of smoking as related to the - management of affect. The Inrenratiotsd Jo+mtal of the Addicttons, 1969, 4, 649-639.  Judson, B.A., Carney, T.M., t Goldstein, A. Naltraone treatment of heroin addiction: Effiacy and safety in a double•bl'usd doaBe ooenparison. Dntf and Akoltol Drpenderies• 1981, 7, 325-346. McMorrow. M.J., & Fota R.M. Nicotine's rok in smoking: An analysis of ttieoeine regulation. Psyeholotiea/ dtrlktae, 1983. fs, 302-327. , Mercer, T.T. T'tikry, M.i., t Chow, H.Y. O9astinj chanaeristia of some compressed-air neublizas. Antericon Indwtrial Xy=ierie A.tsociarion Journal, '16l, 27, W7t. Russell. M.A.H., A Feyerabend. C. Cipreae stnokinj: A depesderxe on high•nieotine, boli. Drut Metabolirm Reviem 1978s a. 29-37. .. Russell, M.A.H., Peto, J., t Patd, tJ.A. The dassification of smokint by a factorial structure of motives. ~ Journal of the Royal Statistiaol Socsety. 1974, 137, 313-346. Stepney, R. Would a medium-nieotiae. low-tar cigarette be less hazardous to health' dritislr Medico! Jo+a- nal, 1981, 2i3, 1292-1296. ~ Zasona, S.v., A Zurcher, L.A., Jr. An analysis of some psychoo-soeial variables associated with smoking * behavior in a college sampk. PsYcholo=ical Reports, 15s 17, 967-97E. . µ~ CJ~ © ZZ i ~