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From pain research to pain treatment: the role of human experimental pain models.

There is no objective measure of a complete pain perception; we can, however, measure different aspects of nociceptive processing and pain perception. Earlier, experimental pain models often only involved induction of cutaneous pain using a single stimulus modality. Recently new experimental models have been developed eliciting various modalities of deep and visceral pain which more closely resemble clinical pain conditions. It is imperative to use multi-modal and multi-structure pain induction and assessment techniques, because a simple model cannot describe the very complex and multi-factorial aspects of clinical pain. Furthermore, it is important to assess pain under normal and pathophysiological conditions. The importance of peripheral and central hyperexcitability for acute and chronic pain has been demonstrated in animals and, to some extent, in humans. However, in spite of our immense knowledge, we still do not know how to prevent and treat this hyperexcitability efficiently. Our understanding of nociceptive mechanisms involved in acute and chronic pain and the effects of anaesthetic drugs or combinations of drugs on these mechanisms in humans may also be expanded using human experimental models. This mechanism-based approach may help us to develop and test therapeutic regimes in patients with acute and chronic pain.

Animals↗

Association between quantitative sensory testing, treatment choice, and subsequent pain reduction in vulvar vestibulitis syndrome.

UNLABELLED: The chronic pain syndrome of vulvar vestibulitis is a major cause of sexual dysfunction, and complete cure is not always achieved. The aim of the study was to determine whether the psychophysical characteristics of systemic pain perception predict treatment choice and outcome. Ninety women with vulvar vestibulitis syndrome were evaluated by using quantitative sensory testing with heat pain threshold measurements and pain scores for suprathreshold stimuli applied to the forearm, blood pressure measurements, and an assessment of the number of other pain disorders. Women were free to choose a surgical procedure (ie, vestibulectomy), one of the possible nonsurgical treatments (eg, biofeedback, cognitive-behavioral therapy, or hypoallergic agents), or to avoid treatment entirely. Eight months later, women reported the success of the treatment on the basis of reduction in the level of vulvar pain. Vestibulectomy demonstrated the best therapeutic effectiveness (chi2, 26.4; P <.0001). Women who chose this type of treatment had lower pain scores (P =.038) and fewer pain syndromes other than the vulvar pain (P =.025). Logistic regression analysis, controlling for the effect of vestibulectomy, indicated that lower experimental pain scores (P =.044), fewer pain disorders (P =.023), and higher systolic blood pressure (P =.039) are predictive variables for reduction of vulvar pain. An assessment of systemic pain perception might be helpful in choosing the optimal treatment and in predicting its success. PERSPECTIVE: The present study suggests that pain perception variables might be of value in the prediction of treatment choice and outcome among women with vulvar vestibulitis.

Adolescent↗

Patients' perceptions of pain management after cardiac surgery in an Australian critical care unit.

OBJECTIVE: The purpose of this study was to investigate patients' perceptions of the effectiveness of a pain management regimen, which consisted of intermittent prn bolus doses of morphine, in a critical care unit after cardiac surgery. DESIGN: This was a escriptive and correlational study. SETTING: This study took place at the cardiothoracic intensive care unit of a major teaching hospital in Sydney, Australia. PATIENTS: The subjects were 102 patients who underwent cardiac surgical procedures. The mean age of the group was 61 years, and 24.5% were females and 75.5% were males. RESULTS: Analysis revealed that patients received limited total amounts of morphine during their critical care stay (mean = 26.7 mg; SD = 13.3; range: 0-68). All activities were associated with increased pain sensation. Patients requiring an internal mammary artery graft experienced increased pain despite receiving greater amounts of morphine. Elderly patients received less morphine and were refused pain killers more often than younger patients. Females found their overall pain experience to be less acceptable than did males. Less than half the participants always communicated their experience of pain to nurses. CONCLUSION: Overall, the majority of participants were reasonably satisfied with their pain experience. However, the following areas need improvement: the assessment and management of pain in relation to gender and age differences and the type of graft/s used; the administration of morphine before activity; and the communication of pain experience by patients.

Adult↗

A comparison of cocaine vs. lidocaine with oxymetazoline for use in nasal procedures.

This study compared the degree of vasoconstriction and anesthesia obtained with cocaine vs. that obtained with a mixture of lidocaine and oxymetazoline (lido/oxy) in healthy, male volunteers. Blood flow was evaluated by laser Doppler flowmetry. Anesthesia was measured with Semmes-Weinstein monofilaments, testing both sensation threshold and pain perception. A greater decrease in blood flow was seen after the administration of lido/oxy than after the administration of cocaine. Pain perception change was not significantly different between treatment groups at 10 minutes after removal of the medication-soaked pledget, but lido/oxy caused a greater decrease in pain perception than cocaine after 50 minutes. No significant difference in sensation threshold change was seen between treatment groups. Lidocaine with oxymetazoline is, therefore, believed to be an effective alternative to cocaine for nasal procedures.

Adult↗

The importance of early recognition of condylar fractures in children: a study of 2 cases.

Maxillofacial fractures in general and mandibular fractures in particular seem to be less common in children than in adults; however, this finding might be influenced by the fact that condylar fractures in children are often undiagnosed and so the true incidence is likely to be higher than that reported in literature. Traumatic lesions of the temporomandibular joint often are overlooked as they can apparently occur with relatively little pain, few clinical signs, and insufficient reaction by the child to alert an adult to the seriousness of the injury. Only 1 to 2 years later, when growth disturbances appear, are they perceived as a problem, but by that time, the dysplastic growth pattern has stabilized and will continue over a period of years. The problem is frequently underestimated because of the difficulties inherent in pediatric pain assessment. The fact that the mechanisms of pain perception in children differ somewhat from adult pain perception mechanisms is one factor that can make pediatric pain assessment difficult. This paper outlines 2 case reports that draw attention to pain in children in the case of temporomandibular joint injury. The inability to assess pain adequately may lead to a delay in diagnosis and treatment and possibly result in future growth disturbances and facial asymmetries.

Child↗

Injectable versus topical anesthesia for cataract surgery: patient perceptions of pain and side effects. The Study of Medical Testing for Cataract Surgery study team.

OBJECTIVE: To compare patient reports of intraoperative pain and postoperative side effects by different anesthesia strategies for cataract surgery. DESIGN: Prospective cohort study. PARTICIPANTS: Men and women 50 years of age and older undergoing 19,250 cataract surgeries at nine centers in the United States and Canada from June 1995 through June 1997. INTERVENTION: Topical anesthesia or anesthesia with injection, with or without sedatives, opioid analgesia, hypnotics, and diphenhydramine (Benadryl). MAIN OUTCOME MEASURES: Patient ratings of intraoperative pain, satisfaction with pain management, and early postoperative side effects (drowsiness, nausea, vomiting, or a combination thereof). RESULTS: Twenty-six percent of surgeries were performed using topical anesthesia alone, and the remainder were performed with peribulbar, retrobulbar, or facial nerve block, or a combination thereof. Local anesthesia by injection with sedatives and diphenhydramine resulted in the lowest reporting of any intraoperative pain (1.3%), with postoperative drowsiness (9.6%) and nausea, vomiting, or both (1.5%) comparable with those administered topical anesthesia alone. Among those receiving topical anesthesia, use of sedatives and opioids reduced reports of any pain during surgery by 56% (95% confidence interval [CI], 34%, 70%), but increased nausea and vomiting (odds ratio, 2.27; 95% CI, 1.26, 4.09) compared with those administered topical anesthesia alone, after adjusting for age, gender, race, American Society of Anesthesiologists risk class, self-reported health status, and duration of surgery. Among those receiving local injections, use of opioids reduced reports of any pain among those receiving sedatives by 37% (95% CI, 15%, 54%), but did not increase postoperative side effects. The use of diphenhydramine among those receiving sedatives decreased reports of any pain by 59% (95% CI, 33%, 75%) and also reduced drowsiness and nausea and vomiting by 57% (95% CI, 48%, 65%) and by 60% (95% CI, 36%, 75%), respectively. Use of hypnotics with sedatives was associated with increased reports of any pain during surgery and increased nausea and vomiting after surgery. CONCLUSIONS: Patient reports of any pain during cataract surgery (5%) and postoperative side effects (16% drowsiness and 4% nausea and vomiting) were low, but varied by anesthesia strategy. Patient perceptions of pain and side effects can be helpful in guiding the appropriate choice of anesthesia strategy.

Administration, Topical↗

The effect of hypnotically induced emotional states on brain potentials evoked by painful argon laser stimulation.

The relationship between pain perception and emotional states is well known. However, the nature of this relationship and how different emotional states affect sensory and cognitive dimensions of pain remains uncertain. Results from experimental investigations are often contradictory, which may be due to methodological difficulties in inducing pain and monitoring physiological responses. In addition, most studies have focused on a single emotion, and data on the relative effects of different emotional states are lacking. In the present study we attempted to eliminate some of these methodological problems. Laser evoked potentials were used as a quantitative correlate to pain perception and were measured in 12 highly hypnotically susceptible subjects during seven conditions: (a) a prehypnotic baseline condition; (b) a neutral hypnotic control condition; (c-e) hypnotically recalled anger, fear, and depression in randomized order; (f) a hypnotically recalled happy condition, and (g) a posthypnotic awake control condition. The pain evoked potentials were significantly decreased in the angry condition and significantly increased in the depressed condition compared with baseline. No differences could be detected for either the happy or the fear-related condition compared with the baseline or neutral hypnotic condition. A significant positive correlation between the subjective intensity of depression and the increase in evoked potentials was found, but none for the other three emotions. The results support earlier findings that clinical depression is related to increased pain perception, and findings that the expression of anger can inhibit the experience of pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Perception of pain and exertion during exercise on a cycle ergometer in chronic pain patients.

HYPOTHESIS: Chronic pain patients (CPP) are generally thought to present with reduced fitness in relation with pain enhancement during exercise. A distortion of exertion perception may coexist, which could lead CPP to reduce physical activities. DESIGN: Case-control study, with a nonrandomized consecutive sample that was age matched. SETTING: A Chronic Pain Unit in a Multidisciplinary Pain Center of a university hospital in a city of > 1,000,000 inhabitants. SUBJECTS: 42 CPP referred for evaluation and 34 controls (staff members and relatives). OUTCOME MEASURES: Fitness index and exertion perception index was obtained by a cycle ergometer test. Trend analysis was performed on pain scores reported on a visual analogue scale during exertion. RESULTS: Male CPP mean fitness index was found to be significantly reduced. No difference in exertion perception was found between groups. Trend analysis of reported pain revealed that 49% of CPP showed a positive trend, 5% a negative trend, and 46% showed no significant trend as exercise intensity increased. There was no significant relation between type of trend and fitness nor exertion perception index. CONCLUSIONS: Only male CPP have a reduced work capacity. Exertion perception seems normal among CPP. The possible distortion of exertion perception as a causal factor in the reduced fitness of CPP has to be rejected. Lack of significant correlation between type of trend of pain while exercising on a cycle ergometer and fitness index shows that one should be careful in proposing that reduced fitness is only related to pain enhancement during exercise in CPP.

Adult↗

Is pain-related fear a predictor of somatosensory hypervigilance in chronic low back pain patients?

Pain-related fear has been found to be associated with increased disability and increased pain perception in patients with chronic low back pain. A possible mechanism by which pain-related fear could lead to increased pain perception is heightened attention to somatosensory sensations. In the present study, chronic pain patients reporting either a high or low level of pain related fear and control participants performed an auditory reaction time task, while occasionally non-painful electrical stimuli--accompanied by threatening instructions--were given to the arm or back. In the primary task condition, participants had to perform the auditory task while ignoring the electrical stimuli. Next, the task was presented under dual task conditions in which participants had to respond both to tones as well as to detection of electrical stimuli. It was hypothesized that for the primary task, high fearful patients would show greater disruption of performance on the auditory task than low fearful patients and controls when stimuli were presented to the back. For the dual task, slower reaction times for the auditory task, in combination with faster detection of electrical stimuli was expected. The hypotheses were not confirmed but patients scoring high on pain-related fear did show an overall increase in reaction time for all conditions of the primary task, with or without simultaneous stimulation. Regression analyses demonstrated that high pain-related fear was associated with increased reaction time to tones both in patients and healthy controls, and that within patients pain-related fear was a better predictor of reaction time to tones than present pain intensity. The findings may be interpreted as showing that patients with elevated levels of pain-related fear habitually attend to somatic sensations, giving less priority to other attention-demanding tasks.

Adult↗

Psychosocial contributions to sex-correlated differences in pain.

Sex-correlated differences in pain perception and behavior have been reported in several studies. Where such differences are found, they are most often in the direction of girls and women reporting more pain than is reported by boys and men. Although biologic, psychologic, and sociocultural factors act interdependently to influence pain responding, most efforts to explain sex-correlated differences in pain have focused on first-order biologic differences between the sexes. The current paper discusses empirical and theoretical literature addressing gender role socialization, cognitive factors, and affective factors associated with sex-correlated differences in pain. We affirm that there is convincing evidence that such psychosocial factors must be taken into account in research on sex-correlated differences in pain. We contend that the use of the dichotomous variable sex as a proxy for presumed biologic aspects of being female or male may obscure the contribution to sex-correlated differences that could be ascribed to the ways in which women and men are socialized with respect to pain perception and pain reporting.

Cognition↗

Dissociation of sensory and affective dimensions of pain using hypnotic modulation.

Understanding the complex nature of pain perception requires the ability to separately analyze its psychological dimensions and their interaction, and relate them to specific variables and responses. The present study, therefore, attempted to selectively modulate the sensory and affective dimensions of pain, using a cognitive intervention, and to assess the possible relationship between these psychological dimensions of pain and changes in physiological responses to the noxious stimuli. In three experiments, normal subjects trained in hypnosis rated pain intensity and pain unpleasantness produced by a tonic heat-pain stimulus (1-min immersion of the hand in 45.0-47.5 degrees C water). Two experiments were designed to test hypnotic suggestions to decrease (Experiment one (Section 2.5.1)), or increase and decrease (Experiment two (Section 2.5.2)) pain affect. Suggestions in Experiment three (Section 2.5.3) were directed towards an increase or decrease in pain sensation. In Experiments one and two (Sections 2.5.1 and 2.5.2), the significant modulation in pain unpleasantness ratings was largely independent of variations in perceived pain intensity. Moreover, in Experiment two (Section 2.5.2), there was a significant correlation between the stimulus-evoked heart-rate increase and ratings of pain unpleasantness, but not of pain intensity, suggesting a direct functional interaction between pain affect and autonomic activation. In Experiment three (Section 2.5.3), suggestions to modulate the sensory aspect of pain produced significant modulation of pain intensity ratings, with secondary changes in pain unpleasantness ratings. Hypnotic susceptibility (Stanford Hypnotic Susceptibility Scale form A) was specifically correlated to pain unpleasantness modulation in Experiment two (Section 2.5.2) and to pain intensity modulation in Experiment three (Section 2.5.3), suggesting that this factor relates to the primary process toward which hypnotic suggestions are directed. The specific pain dimension on which hypnotic suggestions act depends on the content of the instructions and is not a characteristic of hypnosis itself. Results are consistent with a successive-stage model of pain perception (e.g. Wade JB, Dougherty LM, Archer CR, Price DD. Assessing the stages of pain processing: a multivariate analytical approach. Pain 1996;68:157-167) which provides a conceptual framework necessary to study the cerebral representation of pain perception.

Affective Symptoms↗

Multimeasure pain assessment in an ethnically diverse group of patients with cancer.

The purposes of this study were (a) to describe the relationship between pain perception and ethnic identity and socioeconomic status, (b) to evaluate the intercorrelations between pain measures in different ethnic groups, and (c) to determine whether ethnicity or socioeconomic status influences patient's pain control beliefs and satisfaction with the pain management provided. The sample consisted of 51 English-, Korean-, or Spanish-speaking participants experiencing cancer pain who were 18 years and older and were having a Karnofsky score of no less than 30. The Visual Analogue Scale (VAS), Memorial Pain Scale (MPS), and Face Scale (FS) were used to measure pain perception. In all pain analyses, Hispanics, African Americans, and Anglos did not differ significantly. The data suggest that the pain scales used in this study are appropriate for use in a multicultural population.

Adult↗

[Cortical representation of pain].

Contrary to the traditional view that the cerebral cortex is not involved in pain perception an extensive cortical network associated with pain processing has been revealed during the past decades. This network consistently includes the primary (S1) and secondary somatosensory cortices (S2), the insular cortex, and the anterior cingulate cortex (ACC). These cortical areas are organized in parallel and contribute to different dimensions of pain experience. The S1 cortex is mainly involved in discriminative aspects of pain, while the S2 cortex seems to have an important role in cognitive aspects of pain perception. The insula has been proposed to be involved in autonomic reactions to noxious stimuli and in pain-related learning and memory. The ACC is closely related to pain affect and may subserve the integration of general affect, cognition, and response selection. Furthermore, first pain appears to be particularly related to activation of S1 whereas second pain is closely related to ACC activation.

Animals↗

Inhibition by transcutaneous electrical stimulation of noxious heat elicited in human Gasserian ganglion.

During percutaneous thermocoagulation of the Gasserian ganglion for trigeminal pain, the pain perception threshold was established in a series of 25 awake patients by measuring the temperature at the electrode tip within the ganglion during slow increase of the radiofrequency current. Between 42 and 48 degress C pain perception was regularly reported by the patients. A cutaneous-stimulating system was then applied to the trigeminal area which was reported to be painful during the heating. The external stimulation attempted to preferentially stimulate the A afferent nerve fibres. When external stimulation was applied during the heating of the Gasserian ganglion, the pain perception threshold was enhanced in about half of the cases. A transcutaneous electrical stimulation of part of the body not related with the investigated pain sensation did not produce the same inhibitory action in 3 out of 5 cases.

Adult↗

Feasibility and pain control in outpatient hysteroscopy in postmenopausal women: a randomized trial.

BACKGROUND: Three methods of diagnostic hysteroscopy have been tested for both women's compliance and feasibility of procedures in postmenopause. METHODS: Three hundred and sixty-two postmenopausal women were enrolled in a three-arm study: 5 mm diagnostic sheath (Group 1, 119 women), 5 mm sheath with paracervical block (Group 2, 121 women), and 3.5 mm sheath (Group 3, 121 women). CO2 was the distention medium. Both feasibility of hysteroscopy (procedures failed due to stenosis or incomplete distention of cavity) and discomfort of women have been recorded. Pain perception has been measured on a visual numerical rating scale. Statistical analysis was performed by t-test for unpaired samples and chi-square test. RESULTS: Paracervical block was per se painful in 18.2% and bleeding from injection site occurred in 38.8%. Hysteroscopy failure due to stenosis occurred in 9%, 10% and 0.4% of the three groups respectively (p<0.01). Intolerable pain was reported by 17% of women in Group 1, 6% in Group 2 (p<0.05) and in none of Group 3 (p<0.01). Pain score improved from Group 1 to Group 3 (p<0.01). Hysteroscopy was incomplete because of gas leakage in 1.7% of both Group 1 and 2 and in 13.2% of Group 3 (p<0.01). CONCLUSIONS: Pain perception in postmenopausal women was reduced when paracervical block was used, but discomfort was even less with the narrow sheath hysteroscope. The narrow sheath will expose to a high percentage of inconclusive procedures but it can be overcome by changing to the large sheath hysteroscope without affecting patient pain perception.

Aged↗

[Silent myocardial ischemia. Current concepts of pathophysiology and diagnosis].

Silent myocardial ischemia (SMI) is divided into 3 groups: type I: completely asymptomatic patients, type II: patients after acute myocardial infarction with SMI, type III: patients with angina pectoris (AP) and SMI. Pathophysiology on the lack of pain-perception and the cause for high tolerance against pain in SMI-patients has not yet been cleared up. It is most likely that more than one mechanism is involved in every patient, e.g. generally lower pain-perception in SMI-patients, physically counter-regulation in pain, duration and strength of myocardial ischemia. Diagnosis of SMI can be made by exercise- and long-term-ECG, thalliumszintigraphy and coronary angiography, in doing so the pros and cons of the 4 established methods have to be noted. The summary of the findings together with the lack of pain leads to the diagnosis of SMI.

Angina Pectoris↗