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View Delete Self-reported management of pain in hospitalized patients: link between process and outcome.Bovier PA - Am J Med - 15-OCT-2004; 117(8): 569-74From NIH/NLM MEDLINE NLM Citation ID:15465505 (PubMed)Full Source Title:American Journal of MedicinePublication Type:Journal ArticleLanguage:EnglishAuthor Affiliation:Quality of Care Unit, Geneva University Hospitals, Switzerland. patrick.bovier@hcuge.chAuthors:Bovier PA; Charvet A; Cleopas A; Vogt N; Perneger TVAbstract:PURPOSE: Hospitalized patients commonly experience pain. We investigated the association between patients' reported use of recommended pain management practices and overall pain relief. METHODS: All adult patients discharged during a 1-month period from a Swiss teaching hospital were invited to complete a mailed survey that included the Picker patient experience questionnaire, questions on pain relief during hospitalization, and questions on various procedures that are recommended as standards of pain management. RESULTS: Of 2156 eligible patients, 1518 (70%) participated. Sixty-nine percent (n = 1050) had experienced pain during their hospital stay, of whom 71% (n = 697/978) reported complete pain relief. After adjustment for sex, age, general health, and hospital department, pain relief was associated independently with availability of physicians (odds ratio [OR] = 11; 95% confidence interval [CI]: 3.3 to 36 for excellent vs. poor availability), having received information about pain and its management (OR = 2.8; 95% CI: 1.8 to 4.2), regular pain assessment (OR = 1.8; 95% CI: 1.2 to 2.8), modification of pain treatment when ineffective (OR = 3.0; 95% CI: 1.6 to 5.6), and waiting less than 10 minutes for pain medications (OR = 3.5; 95% CI: 1.9 to 6.6). CONCLUSION: Patient reports that recommended pain management procedures had been used were associated with better self-reported pain relief among hospitalized patienPATIENT-REPORTED USE OF RECOMMENDED PRACTICES Reported use of recommended pain management practices varied substantially (Table 1). Of the 564 patients who asked for pain medication, 20% received it immediately, 41% waited 1 to 5 minutes, 20% waited 6 to 10 minutes, and 19% waited 11 minutes or more. Forty-four percent of patients rated the availability of doctors as very good to excellent, and 49% thought the same of nurses. The majority of patients (53%) received enough information about pain and its management, 60% reported regular pain assessment, and 53% were always relieved. When pain was not relieved by treatment, 72% of patients had their treatment changed. Systematic use of a pain assessment tool was reported by only 33% of patients.ASSOCIATIONS WITH PAIN RELIEF Reported use of most pain management recommendations, except for access to a patient-controlled analgesic device, was associated with self-reported complete pain relief (Table 1). Shorter waiting time and better availability of doctors and nurses were also associated with a higher likelihood of complete pain relief.After adjustment for sex, age, general health, and hospital department, five medical care factors remained associated with self-reported complete pain relief, including availability of doctors, information about pain and its management, regular pain assessment, modification of treatment, and short average waiting time before receiving a pain killer (Table 3). When none of the five factors was reported, only 11% of patients noted pain relief, but when all were reported, 95% of patients did (Figure).Table 3 . Medical Care Factors Associated with Self-Reported Complete Pain Relief in a Multivariate Logistic Regression Model Characteristic Odds Ratio* (95% Confidence Interval) Availability of medical doctor Poor 1.0 – Fair 2.3 (0.8–7.0) Good 4.0 (1.4–11) Very good 5.9 (2.0–17) Excellent 11 (3.3–36) Received information about pain and its management (definitely vs. to some extent or did not receive) 2.8 (1.8–4.2) Regular assessment of pain (vs. irregular or none) 1.8 (1.2–2.8) Treatment modification (vs. no modification) Pain was always relieved 11 (5.8–20) Treatment was modified 3.0 (1.6–5.6) Average waiting time before receiving a pain medication Never asked 3.7 (1.9–7.2) 0–10 minutes 3.5 (1.9–6.6) >10 minutes 1.0 – * Adjusted for age, sex, general health, and type of medical service. Figure Relation between the number of recommended pain management processes reported by patients and self-reported pain relief among hospitalized patients. Factors included very good or excellent availability of medical doctor; definitely received information about pain and its management; regular assessment of pain; modification of treatment or pain always relieved; never asked for a pain medication; and waiting time of 10 minutes or less. DISCUSSIONWe found that reported use of recommended pain management procedures during routine care was associated with better self-reported pain relief among hospitalized patients. A majority of patients (69%) said they had experienced pain, many of whom had inadequate pain relief. Pain relief was more common in patients who reported they had received information about pain and its management, regular pain assessment, modification of pain treatment when necessary, and short average waiting time before receiving a requested pain medication. These results confirm that several of the pain management processes recommended by international guidelines are associated with better self-reported pain relief among patients. However, one process indicator—use of a patient-controlled analgesic device (23)—was not associated with pain relief. We believe that process indicators associated with good outcomes are most useful for monitoring quality of care.We also found that women, patients who reported being in poor health, and patients who felt depressed at the time of the survey were more likely to report unsatisfactory pain relief. We cannot determine whether these characteristics identify patients who are less tolerant of pain or who are less likely to receive effective analgesia in the hospital.From the patient's standpoint, the availability of doctors and nurses appears to affect pain management. In our study, perceived availability of doctors was associated significantly with pain relief, whereas the availability of nurses was related to pain relief in univariate analysis but not after adjustment for specific medical care variables. A likely explanation is that medical care is mostly carried out by nurses, who perform regular pain assessments and respond to patients who request a pain medication. Thus, nurse availability matters because it is a requirement for successful implementation of pain management guidelines.Previous studies suggest that a good relationship between patient and physician is linked with successful pain management (24, 25). For a patient, being given undivided attention and being shown empathy by one's doctor can have an analgesic effect (24). Our results suggest that the availability of doctors may influence pain relief through mechanisms that were not captured by the questionnaire, such as the prescription of effective doses of analgesics.We relied exclusively on patient reports of pain relief and pain-related processes using a survey that was administered several weeks after hospitalization. This raises the issue of recall bias. Nevertheless, retrospective pain assessments appear to be valid for a 3-month period (26). Because we relied on patient reports, we were not able to measure some important pain management processes, such as type of analgesia or dosage used. Furthermore, our questions may not have allowed patients to discriminate between pain and other types of suffering, such as emotional distress, which are unlikely to be alleviated by analgesics. Finally, as with any cross-sectional study, causal interpretation of our findings must be done cautiously.However, we studied a large sample of patients from several services at a general hospital, and the participation rate was reasonable. Finally, our results were based on the views of patients, whose judgment is essential when dealing with pain management (9).In conclusion, we found that at a large general teaching hospital, the majority of patients experienced pain during hospitalization. Pain relief was inadequate in a substantial minority. Recommended pain management practices were applied inconsistently, even though many were associated with better pain relief. Hospitals should be encouraged to apply these practices more consistently.Acknowledgment The authors wish to thank the Quality of Care Program of Geneva University HospitalsPAIN AND REGIONAL ANESTHESIA--------------------------------------------------------------------------------Experimental Pain Models Reveal No Sex Differences in Pentazocine Analgesia in HumansRoger B. Fillingim, Ph.D.,*Timothy J. Ness, M.D., Ph.D.,†Toni L. Glover, M.A., R.N.,‡Claudia M. Campbell, B.A.,§Donald D. Price, Ph.D.,‖Roland Staud, M.D.#* Associate Professor, University of Florida College of Dentistry, Public Health Services and Research, and Gainesville Veterans Affairs Medical Center. † Professor, University of Alabama at Birmingham, Department of Anesthesiology, Birmingham, Alabama. ‡ Research Nurse, University of Florida College of Dentistry, Public Health Services and Research. § Graduate Assistant, University of Florida College of Dentistry, Public Health Services and Research, and University of Florida, Department of Clinical and Health Psychology. ‖ Professor, University of Florida College of Dentistry, Department of Oral Surgery. # Associate Professor, University of Florida, Department of Medicine.Received from the University of Florida and the Gainesville Veterans Affairs Medical Center, Gainesville, Florida.Submitted for publication October 17, 2003.Accepted for publication January 22, 2004.--------------------------------------------------------------------------------This material is the result of work supported with resources and the use of facilities at the Malcom Randall Veterans Affairs Medical Center, Gainesville, Florida. Supported by grant No. NS41670 and General Clinical Research Center Grant No. RR00082 from the National Institutes of Health, Bethesda, Maryland.Address reprint requests to Dr. Fillingim: University of Florida College of Dentistry, Public Health Services and Research, 1600 Southwest Archer Road, Room D8-44A, P. O. Box 100404, Gainesville, Florida 32610-0404. Address electronic mail to: rfilling@ufl.edu. Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org.Background: Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to κ-agonist–antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in κ-agonist–antagonist effects from studies of experimentally induced pain in humans is lacking.Methods: Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order.Results: Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain.Conclusions: These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.IntroductionOPIOID analgesic responses are characterized by substantial individual differences, and an understanding of the factors contributing to this variability is of tremendous clinical and scientific importance. In this regard, sex-related influences on responses to opioids have received increasing attention in recent years. A recent review indicated that women consume significantly less opioid medication postoperatively than men do. [1] However, because many of these studies failed to assess pain, it is difficult to determine whether the lower opioid consumption in women was due to enhanced analgesia or other factors (e.g., side effects). A more recent investigation of nearly 2,300 patients found that female patients had similar or lower postsurgical pain ratings than male patients even though they consumed 23.5, 37.5, and 43% less opioid than the male patients on postoperative days 1, 2, and 3, respectively. [2] In addition to these findings from postoperative studies, which almost exclusively involve μ opioids, sex differences in μ-opioid analgesia have been demonstrated using experimental pain models. Sarton et al. [3] examined morphine analgesia among 10 healthy women and 10 healthy men using an electrical pain model. Women showed greater analgesic potency but slower onset and offset of analgesia. These authors had previously reported greater morphine-induced respiratory depression among women than among men. [4] [5] Zacny [6] used two experimental pain models (pressure and cold pressor pain) to determine sex differences in analgesic responses to three μ-opioid agonists, morphine, meperidine, and hydromorphone, in a sample of 16 male and 15 female patients. No sex differences in analgesia emerged for pressure pain; however, analgesic responses for all three drugs were greater among female patients for cold pressor pain. Therefore, evidence from both laboratory and clinical studies suggests that women may experience greater μ-opioid analgesia than men.A series of studies that have garnered considerable scientific and media attention has investigated sex differences in analgesic responses to κ-agonist–antagonist medications using an oral surgery model. These investigators first reported greater analgesic responses among female patients compared with male patients for pentazocine but not morphine. [7] [8] Subsequently, they demonstrated more prolonged analgesia among female patients than among male patients with the κ-agonist–antagonists nalbuphine and butorphanol. [9] More recently, they have demonstrated that after low-dose nalbuphine (5 mg), pain ratings increased in men but showed no change in women, whereas higher doses (10 and 20 mg) produced analgesia of longer duration in women than in men. [10] These results indicate more robust analgesic responses to κ-agonist–antagonist medications among women but no differences in morphine analgesia. We recently demonstrated that the melanocortin-1 receptor gene (MC1R) moderated analgesic responses to pentazocine among women but not among men; however, there was no overall sex difference in pentazocine analgesia. [11] Therefore, sex differences in responses to κ-agonist–antagonists have yet to be replicated in other clinical assays or using experimental pain models.The main purpose of the current study was to investigate sex differences in pentazocine analgesia using multiple, well-validated experimental pain models. Healthy women and men underwent three experimental pain procedures (heat pain, pressure pain, and ischemic pain) before and after double-blind administration of pentazocine and saline placebo. Laboratory pain models were used because they allow greater stimulus control and the effects of pentazocine could be tested in the absence of other medications that are administered in most postoperative pain models. Based on the previous findings of Gear et al., [7] [8] we hypothesized that women would show greater analgesic responses than men.Materials and MethodsSubjectsSubjects included 41 women and 38 men recruited via posted advertisements. All participants were healthy nonsmokers and were free of clinical pain, psychiatric disturbance, substance abuse, or use of centrally acting medications. Subjects refrained from any over-the-counter medication use for at least 24 h before testing. Nineteen (46.3%) of the women were taking oral contraceptives. Based on our previous findings, [11] subjects (five women, nine men) with two variant alleles on the MC1R gene were excluded from the analyses. Subjects were paid $50 per experimental session for their participation.General Experimental ProceduresAll subjects participated in two experimental sessions, one involving administration of pentazocine and the other involving saline placebo, in randomly counterbalanced order. For women, all sessions were conducted during the follicular phase of the menstrual cycle, between days 4 and 10 after the onset of menses. Half of the women participated in the two experimental sessions within the a single menstrual cycle, separated by 2–7 days, and the other half participated across two sequential menstrual cycles, in which case the sessions were separated by approximately 28 days. To maintain consistent intervals across sex, 19 men participated in the two sessions within 1 week, and 16 men participated with the longer interval (i.e., 4 weeks).Before the experimental sessions began, all subjects provided verbal and written informed consent and completed a series of health and psychological questionnaires to ensure that all subjects were free of any medical conditions, psychological conditions, or both. The two experimental sessions were identical, except that pentazocine was administered in one session and saline was administered in the other. All sessions were conducted by two experimenters, either two women or one woman and one man. Each experimental session started with insertion of an intravenous cannula for drug administration followed by a 15-min rest period, during which blood pressure and heart rate were monitored. Next, predrug experimental pain testing was performed, including assessment of thermal pain, pressure pain, and ischemic pain (described in detail in the next section, Pain Testing Procedures). After the predrug pain testing, a 15-min rest period was observed, followed by double-blind intravenous bolus administration of either pentazocine (0.5 mg/kg) or saline, in randomized order. Fifteen minutes after drug administration, pain testing was repeated in a manner identical to the predrug testing. A timeline depicting the experimental session is presented in figure 1. Adverse effects reported by subjects, observed by experimenters, or both were also recorded. All procedures were approved by the University of Florida Health Science Center’s Institutional Review Board (Gainesville, Florida).Fig. 1. Timeline of the experimental session. The boxed text presents the components of the experimental session, and the numbers below the timeline indicate the approximate time in minutes at which experimental procedures were conducted. The lines linking thermal pain to pressure pain indicate that these two procedures were conducted in counterbalanced order.Pain Testing ProceduresThe following experimental pain procedures were conducted before and after drug administration. Pressure and thermal pain were delivered first in counterbalanced order, separated by a 5-min rest period. Ischemic pain always occurred last to reduce the possibility of carryover effects. Before each pain procedure, digitally recorded instructions were played for the subject.Pressure Pain Threshold. A handheld algometer (Pain Diagnostics and Therapeutics, Great Neck, NY) was used to assess pressure pain threshold (PPT). Mechanical pressure was applied using a 1-cm2 probe. A relatively slow application rate of 1 kg/s was used to reduce artifact associated with reaction time. Subjects were instructed to report when the pressure first became painful. PPTs were assessed at three sites: the center of the right upper trapezius (posterior to the clavicle), the right masseter (approximately midway between the ear opening and the corner of the mouth), and the right ulna (on the dorsal forearm, approximately 8 cm distal to the elbow), with the order of site presentation counterbalanced. PPTs were assessed three times at each site, and the average of the three assessments was determined and used in subsequent analyses.Thermal Pain ProceduresThreshold and Tolerance. The first thermal procedure involved assessment of heat pain threshold and tolerance. Contact heat stimuli were delivered using a computer-controlled Medoc Thermal Sensory Analyzer (TSA-2001; Ramat Yishai, Israel), which is a Peltier element-based stimulator. Temperature levels were monitored by a contactor-contained thermistor and returned to a preset baseline of 32°C by active cooling at a rate of 10°C/s. The 3 × 3-cm contact probe was applied to the right ventral forearm. In separate series of trials, warmth thresholds, heat pain thresholds, and heat pain tolerances were assessed using an ascending method of limits. From a baseline of 32°C, probe temperature increased at a rate of 0.5°C/s until the subject responded by pressing a button to indicate when he or she first felt pain and when he or she no longer felt able to tolerate the pain. This slow rise time was selected as a test of pain evoked mainly by stimulation of C-nociceptive afferents, as has been previously demonstrated. [12] [13] Four trials of heat pain threshold (HPTh) and heat pain tolerance (HPTo) were presented to each subject. The position of the thermode was altered slightly between trials (although it remained on the ventral forearm) to avoid either sensitization or response suppression of cutaneous heat nociceptors. For each measure, the average of all four trials was computed for use in subsequent analyses.Temporal Summation of Thermal Pain. After a 5-min rest period, the temporal summation procedure was conducted. This procedure involved administration of brief, repetitive, suprathreshold heat pulses to assess first and second pain and temporal summation of the latter. [14] Subjects rated thermal pain intensity of 10 repetitive heat pulses applied to the right dorsal forearm. The target temperatures were delivered for less than 1 s, with a 2.5-s interpulse interval during which the temperature of the contactor returned to a baseline of 40°C. Subjects were asked to rate the peak pain for each of the 10 heat pulses. Because subjects vary in their responses to heat pain, we examined temporal summation at two different stimulus intensities. This increased the likelihood that at least one set of stimuli would be at least moderately painful but tolerable for the majority of subjects. Therefore, two sets of target temperatures, 49° and 52°C, were used. Subjects were instructed to verbally rate the intensity of each thermal pulse using a numerical rating scale as previously described, [15] on which 0 represented no sensation, 20 represented a barely painful sensation, and 100 represented the most intense pain imaginable. Subjects were told that the procedure would be terminated when they reported a rating of 100, when 10 trials had elapsed, or when they wished to stop. Two measures from the temporal summation procedure at each temperature were used in subsequent analyses. The rating of the first trial was selected to represent a measure of first pain, and the rating of the fourth trial was selected to reflect summated second pain. These ratings were chosen for two reasons. First, using similar methods, it has been established that the most intense pain from the first pulse is that of “first pain” and that the most intense pain from the third or fourth pulse is that of “second pain.” [14] [16] This pattern results from a progressive suppression of first pain and temporal summation of second pain throughout a train of four heat pulses. Second, inspection of the mean ratings for each trial indicated that the increase in ratings was most robust through trial 4, suggesting that trial 4 best reflected temporal summation.Modified Submaximal Tourniquet ProcedureAfter the first two pain procedures, a 5-min rest period was observed, after which subjects underwent the modified submaximal tourniquet procedure. [17] [18] Next, the right arm was exsanguinated by elevating it above heart level for 30 s, after which the arm was occluded with a standard blood pressure cuff positioned proximal to the elbow and inflated to 240 mmHg using a Hokanson E20 Rapid Cuff Inflator (D.E. Hokanson, Bellevue, WA). Subjects then performed 20 handgrip exercises of 2-s duration at 4-s intervals at 50% of their maximum grip strength. Subjects were instructed to report when they first felt pain (ischemic pain threshold [IPTh]) and then to continue until the pain became intolerable (ischemic pain tolerance [IPTo]), and these time points were recorded. Every 30 s, subjects were prompted to alternately rate either the intensity or the unpleasantness of their pain using joint numerical (0–20) and verbal descriptor box scales. [19] An uninformed 15-min time limit was observed. In addition to IPTh and IPTo, two total pain scores were created, one for pain intensity and one for pain unpleasantness, by summing all ratings obtained during the procedure. To replace missing values created by subjects terminating the procedure before the time limit, the last rating provided was carried forward.DiscussionThis study examined sex differences in pain perception and pentazocine analgesia using three commonly used experimental pain models. The results indicate sex differences in baseline thermal and pressure pain responses but no differences in ischemic pain measures. This is generally consistent with previous research on sex differences in experimental pain perception, which have reported greater pain sensitivity among female subjects, with the magnitude of the difference varying across pain stimuli. [20] [21] [22] The current results suggest that 0.5 mg/kg intravenous pentazocine produced significant analgesic responses on most pain measures for both women and men; however, in contrast to our hypotheses, no sex differences in pentazocine analgesia emerged on any of the pain tasks. Similarly, no sex differences in adverse effects were observed. Although the analgesic effects of pentazocine have been demonstrated in other experimental pain models, sex differences in pentazocine analgesia were not addressed in these previous studies. Two of the four previous investigations included only male subjects, [23] [24] and the two that included both women and men did not comment on sex differences in analgesic responses. [25] [26] Interestingly, Kobal et al. [25] found sex differences in the pharmacokinetics of pentazocine, with a longer half-life and mean residence time among women than men. However, they did not report on sex differences in analgesic responses. The most compelling evidence for sex differences in pentazocine analgesia comes from two clinical studies conducted at the University of California at San Francisco using an oral surgery pain model. Gordon et al. [8] reported that women (n = 22) experienced greater analgesia from 30 mg intravenous pentazocine compared with men (n = 12), and there was a trend toward more prolonged analgesia among women. In a subsequent study using the same methodology, Gear et al. [7] reported more robust pentazocine analgesia among women (n = 10) than among men (n = 8) at 10 and 30 min after medication administration.Multiple factors may explain the discrepancy between the current findings and those of Gear et al. Perhaps the most obvious difference is the pain assay used. The pain after oral surgery differs from our experimental pain procedures in several substantial ways. First, postoperative dental pain includes a strong inflammatory component, and κ-opioid agonists produce peripheral antiinflammatory effects [27] [28] [29] [30] ; therefore, sex differences in the antiinflammatory action of pentazocine could contribute to the differences in opioid analgesia in postoperative pain models. Second, the oral surgery model involved premedication with diazepam, nitrous oxide, and a local anesthetic, and these drugs could influence pentazocine analgesia. For example, diazepam has been found to bind to κ-opioid receptors in vitro, [31] and systemically administered diazepam can attenuate both μ- and κ-opioid analgesia. [32] Moreover, benzodiazepine antagonism potentiated morphine analgesia in the oral surgery model. [33] In addition to benzodiazepines, nitrous oxide is thought to produce analgesia at least in part by activating κ-opioid receptors. [34] [35] Whether these drug interactions contribute to sex differences in pentazocine analgesia is not known. Third, in the oral surgery model, drug was delivered when the patients were experiencing at least moderate pain, whereas our subjects were pain free at the time of drug administration. This is potentially important because the effects of opioids may differ when administered in the presence of pain and inflammation versus the pain-free state.Other methodologic factors could also contribute to the discrepancy in findings. For example, we dosed by weight (0.5 mg/kg), which resulted in men receiving higher amounts of pentazocine in our study compared with the fixed dosage (30 mg) used in the University of California at San Francisco studies. Differences in the timing of postdrug assessments are unlikely to account for the conflicting results because we started our postdrug pain testing 15 min after drug administration, and it was completed within 60 min of drug administration. This timing is consistent with the period reported on in the University of California at San Francisco studies because they reported sex differences at 10 min and at 30 min in one study [7] and from 30 to 170 min in another. [8] However, Kobal et al. [25] reported that 30 mg intravenous pentazocine had a longer half-life among women than among men, although their fixed dosing resulted in women receiving a higher dose per unit body weight. Nonetheless, the longer residence time of pentazocine among women is interesting given that the only tendency toward greater analgesia for women in our data emerged for ischemic pain, the pain task that was conducted after the longest postdrug delay. In addition, previous research with morphine has shown more rapid onset of analgesia in men and longer duration of analgesia in women, [3] and nalbuphine, another κ-agonist–antagonist, produced more prolonged analgesia in women compared with men. [9] Therefore, future research exploring sex differences in opioid analgesia should evaluate sex differences in the onset and offset of drug effects.In addition, sample selection may contribute to the different study outcomes. Participants in our protocol were recruited specifically for a study involving experimental pain testing and analgesics and may represent a different population than patients presenting for third molar extraction, who are then offered participation in a clinical protocol. These additional methodologic differences notwithstanding, variability in the pain assays seems most likely to account for the differences in findings. This could be an important finding because it indicates that sex differences in analgesic responses to pentazocine and perhaps other opioids may be limited to certain types of pain. Additional research is needed to determine the conditions under which sex differences in opioid analgesia are most likely to emerge.The use of multiple pain assays in the current study yielded additional important results. First, consistent with studies of μ-opioid agonists on multiple pain tests, [16] [36] pentazocine produced larger and more reliable effects on pain predominantly associated with C-nociceptor stimulation (HPTh, HPTo, ratings of the fourth heat pulse) than pain predominantly associated with A-δ nociceptor stimulation (ratings of the first heat pulse). Also, the largest analgesic effects emerged on measures of ischemic pain, a form of tonic muscle pain that reflects a combination of A and C nociceptors from deep tissue. This form of tonic pain may better simulate many types of clinical pain, as argued by Smith et al. [37] In addition, analgesic responses showed low correlations across pain modalities (table 3). For women, analgesic responses assessed using heat pain measures were significantly correlated with analgesia determined via ischemic and pressure pain assays; however, these correlations were low in magnitude and not significantly different from the correlations in men, and no other significant correlations emerged. A similar pattern of results has been reported for baseline pain responses, in which measures based on different pain modalities are modestly correlated at best. [38] [39] This suggests that despite significant analgesic responses across all pain modalities, analgesic sensitivity determined using one type of pain is a poor predictor of analgesic response to other types of pain and that different mechanisms underlie analgesic responses for different types of pain. An important practical implication of these findings is that multiple pain assays will be required to fully characterize the analgesic effects of many drugs.Several limitations of the current study deserve mention. First, analgesic responses assessed using experimental pain models may not accurately reflect the analgesic responses that occur in the clinical setting. Experimental models offer several advantages, including control over stimulus parameters, the ability to test multiple pain modalities in the same sample, and freedom to examine analgesic responses in the absence of other medications or tissue pathology. However, the clinical relevance of analgesic responses measured against experimentally induced pain has yet to be empirically determined. As discussed in the third paragraph of the Discussion, sex differences in the analgesic effects of pentazocine may differ for inflammatory postoperative pain compared with nociceptive experimental pain. Therefore, these results do not refute the existence of sex differences in the analgesic effects of pentazocine for postoperative pain; rather, these findings suggest that sex differences in pentazocine analgesia may be specific to postoperative pain and do not represent a general phenomenon. To test this hypothesis, one would need to evaluate pentazocine analgesia against both experimental and postoperative pain in the same sample of women and men.Second, our sample consisted of healthy young adults whose responses may not generalize to other populations that may differ in health status, age, or other relevant variables. Third, we only tested one dose of pentazocine over a limited time period and were unable to determine whether sex differences are present at other doses or whether time course influences sex differences. Similarly, we did not collect any pharmacokinetic or pharmacodynamic data; therefore, we were unable to determine whether there were sex differences in duration of action or plasma concentrations of the drug. As mentioned above, our doses and timing were similar to those reported previously in studies that demonstrated sex differences in pentazocine analgesia [7] [8] ; however, these investigators have also demonstrated that sex differences in responses to other κ-agonist–antagonists are dose dependent, [10] and others have reported sex differences in the kinetics of pentazocine. [25] Additional research to determine the importance of dose as well as pharmacokinetic and pharmacodynamic factors to sex differences in opioid analgesia is needed.ConclusionThese limitations notwithstanding, we tested a substantially larger sample than did previous studies, which provided sufficient power to detect a sex difference of moderate magnitude. 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Gear RW , Miaskowski C , Heller PH , Paul SM , Gordon NC , Levine JD : Benzodiazepine mediated antagonism of opioid analgesia . Pain 1997 ; 71 : 25–9 Abstract 34. Quock RM , Best JA , Chen DC , Vaughn LK , Portoghese PS , Takemori AE : Mediation of nitrous oxide analgesia in mice by spinal and supraspinal kappa-opioid receptors . Eur J Pharmacol 1990 ; 175 : 97–100 Abstract 35. Quock RM , Mueller J : Protection by U-50,488H against beta-chlornaltrexamine antagonism of nitrous oxide antinociception in mice . Brain Res 1991 ; 549 : 162–4 Abstract 36. Price DD , Staud R , Robinson ME , Mauderli AP , Cannon R , Vierck CJ : Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients . Pain 2002 ; 99 : 49–59 Abstract 37. Smith GM , Egbert LD , Markowtiz RA , Mosteller F , Beecher HK : An experimental pain method sensitive to morphine in man : The submaximum effort tourniquet technique . J Pharmacol Exp Ther 1966 ; 154 : 324–32 Citation 38. Janal MN , Glusman M , Kuhl JP , Clark WC : On the absence of correlation between responses to noxious heat, cold, electrical and ischemic stimulation . Pain 1994 ; 58 : 403–11 Abstract 39. Lautenbacher S , Rollman GB : Sex differences in responsiveness to painful and non-painful stimuli are dependent upon the stimulation method . Pain 1993 ; 53 : 255–64 Abstract Patient expectations for pain relief in the ED.Fosnocht DE - Am J Emerg Med - 01-JUL-2004; 22(4): 286-8From NIH/NLM MEDLINE Results A total of 752 patients were enrolled in the study. Complete data were available for 522 patients with pain and 144 patients without pain. The patient group without pain tended to be older and had a higher percentage of men than the patient group presenting with pain. Patient demographics are displayed in Table 1 . TABLE 1. Demographics for Patients With Pain and Patients Without Pain Total Age 18–54 yrs Age >54 yrs Mean Age (95% CI) Female Male Patients with pain 522 453 (87%) 69 (13%) 38 (±1.3) 269 (52%) 253 (48%) Patients without pain 144 106 (74%) 38 (26%) 45 (±3.1) 64 (44%) 80 (56%) Patients presenting to the ED with pain had a mean expectation for pain relief of 72% (95% CI 70 to 74). This was not significantly different from patients presenting to the ED without pain who had a mean expectation for pain relief of 74%, (95% CI 71 to 77) if they had presented with a painful injury or illness. Ninety-four of 522 (18%) patients with pain and 22 of 144 (15%) patients without pain expected complete relief of pain in the ED (VAS measurement of pain RELIEF = 100 mm). Of those patients presenting with pain, there was no difference in the mean expectation for pain relief in those with mild (VAS 1–33 mm), moderate (VAS 34–66 mm), or severe (VAS > 66 mm) pain. Mean expectations for pain relief for those patients presenting with mild, moderate, and severe pain are reported in Table 2 . Pain intensity at presentation correlated poorly with patient expectations for pain relief R = 0.150 (95% CI 0.07 to 0.23).TABLE 2. Expectations for Pain Relief VAS (95% CI) Those With Mild, Moderate, and Severe Pain * Mild pain VAS 1–33 mm, moderate pain VAS 34–66 mm and severe pain VAS >66 mm. Initial Pain Severity* Number Mean % Expectation for Pain Relief Range Mild pain 94 68 (63–73) 2 to 100 Moderate pain 157 71 (68–74) 15 to 100 Severe pain 271 75 (73–78) 1 to 100 Age and gender were not associated with differences in patient expectations for pain relief in the ED for patients with or without pain. Patient expectations for pain relief by age and gender are displayed in Table 3 . TABLE 3. Mean % Expectation for Pain Relief VAS (95% CI) by Age and Gender Age 18–54 Age >54 Females Males Patients without pain 74 (70–78) 73 (66–80) 76 (72–80) 73 (68–78) Patients with pain 73 (71–75) 70 (64–76) 73 (70–76) 72 (69–75) Discussion Relieving pain is one of the oldest and most basic principles of medicine. Despite an increasingly scientific understanding of pain and the availability of effective analgesics, inadequate pain relief is common for patients in the ED. Poor understanding of patient expectations for pain relief may contribute to poor analgesia in the ED. In addition, patient expectations for pain relief may play an important role in the development of standardized outcomes measures for pain relief in the ED setting. Various authors have suggested that patient expectations strongly influence patient’s experience of pain and satisfaction with care.[17] [18] [23] We found that ED patients have high expectations for pain relief. Patients with pain reported a mean expectation for pain relief of 72% with 18 % of patients expecting complete relief of their pain. This contrasts with studies performed in the surgical setting where postoperative patients have low expectations for pain relief.[14] [24] However, the number of patients expecting complete relief of pain is consistent with a report by Beel et al who found that in an ED population with acute fractures, 25% of patients wanted complete relief of their pain.[25] Surprisingly, ED patients’ expectations for pain relief do not appear to vary based on their initial pain intensity. Patients’ mean expectation for pain relief increased from 68% for those with mild pain to 71% for moderate pain and 75% for severe pain. These differences were not statistically significant and the corresponding correlation of pain intensity at presentation with expectations for pain relief was only slight at R = 0.150. In addition, the difference in expectations for pain relief was only 7 % (7 mm) between those with mild and those with severe pain. This difference is unlikely to be clinically significant based on the work of Todd et al and Gallagher et al who have established that 13 mm is the threshold for clinically significant differences in pain relief using a 100 mm VAS.[26] [27] ED patient expectations for pain relief may in fact be independent of an acute painful injury or illness. Our evaluation of ED patients presenting without pain revealed that they would expect 74% of their pain to be relieved if they had presented with a painful injury or illness. This is similar to those patients presenting with pain and suggests patients’ expectations for pain relief may be determined before the acute event that brings them to the ED. Factors such as previous pain experience and prior treatment of pain in an ED or other medical setting that may influence patient expectations for pain relief are deserving of further study.Age has been shown to influence patient perceptions of pain and may have an impact on patient expectations for pain relief in the ED. Studies in surgical settings show that differences exist in patient expectations for pain treatment between younger and older patients, with older patients having less pain, but requiring the same amount of analgesia as younger patients.[28] In an ED setting elderly patients were found to report lower pain intensity to a standardized painful stimulus than younger patients.[29] However, we found no significant differences in patient expectations for pain relief between younger and older patients.Gender has also been reported to impact patient’s experience of pain in various studies. Nevin has evaluated the relationship between pain and gender and concluded that women have lower pain thresholds, lower pain tolerance, and report greater pain intensity than men.[30] Beel et al studied 107 adults with acute long-bone fractures and reported that men were more likely than women to prefer no pain treatment in the ED.[25] However, gender-related expectations for pain relief were not formally quantified in any of these studies. Our study of ED patients shows no differences in patient expectations for pain relief between men and women, with both groups expecting a high degree of pain relief in the ED.This study has several limitations. First, this study represents a convenience sample of patients. This may have led to selection bias in the enrollment of patients and may limit the extent to which the results may be generalized. The total number of patients presenting to the ED with and without pain during the study period is unknown. However, an attempt was made to enroll all patients meeting the study criteria when research associates were available for data collection. The rate of refusal for patients approached to be enrolled in the study was less than 1%. Second, demographics between patients with pain and patients without pain are similar, but not identical. This may have led to inaccurate conclusions about the similarities or differences in expectations for pain relief between these subgroups. Third, we made no attempt to limit inclusion by acuity of pain or type of injury or illness. Pain duration and chief complaint may impact patient expectations for pain relief in the ED. Although our results are likely to be representative of an overall ED population, they may not accurately reflect expectations for pain relief of patients with specific injuries or illnesses. Finally, this study was conducted in a single university ED and the results may not be applicable to other practice settings.In summary, patients expect a high degree of pain relief in the ED with a mean expectation of 72 % relief of their pain. Eighteen percent of patients expect complete relief of pain. Patient expectations for pain relief are poorly correlated with initial pain intensity. ED patients without pain reported similar expectations for pain relief if they had presented with pain, suggesting that patient expectations for pain relief may be independent of the presence of an acute injury or illness. Patient age and gender do not appear to influence patient expectations for pain relief in the ED.References1. JCAHO. Pain Management Standards for 2001 Joint Commission on Accreditation of Healthcare Organizations; 2001. p. 1.2.7-8. 2. Goodacre SW, Roden RK. A protocol to improve analgesia use in the accident and emergency department. J Accid Emerg Med 1996;13:177-9. Abstract 3. 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