Quantitative assessment of experimental pain perception: multiple domains of clinical relevance.
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Humans↗
Biomedical subjects
Roger B Fillingim
Publications and source records attributed to Roger B Fillingim.
Cluster analysis of multiple experimental pain modalities.
Identifying individual differences in pain is an important topic; however, little is known regarding patterns of responses across various experimental pain modalities. This study evaluated subgroups emerging from multiple experimental pain measures. One hundred and eighty-eight individuals (59.0% female) completed several psychological instruments and underwent ischemic, pressure, and thermal pain assessments. Thirteen separate pain measures were obtained by using three experimental pain modalities with several parameters tested within each modality. The pain ratings and scores were submitted to factor analysis that identified four pain factors from which Pain Sensitivity Index (PSI) scores were computed: heat pain (HP), pressure pain (PP), ischemic pain (IP), and temporal summation of heat pain (TS). Cluster analyses of PSI scores revealed four distinct clusters. The first cluster demonstrated high overall pain sensitivity, the second cluster revealed high TS, the third cluster showed particular insensitivity to IP and low sensitivity across pain modalities except PP, and the fourth cluster demonstrated low sensitivity to PP. Significant correlations were found between psychological measures and Index scores and those differed by sex. Cluster membership was associated with demographic variables of ethnicity and sex as well as specific psychosocial variables, although cluster differences were only partially explained by such factors. These analyses revealed that groups respond differently across varied pain stimuli, and this was not related solely to demographic or psychosocial factors. These findings highlight the need for future investigation to identify patterns of responses across different pain modalities in order to more accurately characterize individual differences in responses to experimental pain.
Adolescent↗
Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis.
PURPOSE: We quantified differences in somatic and visceral sensation in healthy subjects and subjects with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 13 subjects with IC and 13 healthy subjects answered psychological questionnaires and underwent psychophysical testing of thermal and pressure thresholds for sensation as well as the ischemic forearm test of pain tolerance. A subset of subjects also underwent bladder sensory testing with the determination of 3 consecutive cystometrograms. Ratings of intensity and unpleasantness were determined. RESULTS: Subjects with IC were significantly more sensitive to deep tissue measures of sensation related to pressure, ischemia and bladder than healthy subjects. Cutaneous thermal pain measures were similar in the 2 groups. Psychological measures indicated higher reactivity in subjects with IC. CONCLUSIONS: Similar to other visceral pain disorders, such as irritable bowel syndrome, hypersensitivity to somatic stimuli was noted in subjects with IC. This suggests altered central mechanisms in the processing of sensory events from the bladder.
Adult↗
Menstrual cycle affects bladder pain sensation in subjects with interstitial cystitis.
PURPOSE: Using psychophysical methods we compared the effect of the menstrual cycle on bladder sensation in subjects with the diagnosis of interstitial cystitis (IC) and in controls. MATERIALS AND METHODS: Female participants with normal menstrual cycles, including 7 with IC and 8 healthy controls, were recruited into this study. They completed daily diaries related to bladder pain and other body pain, and tracked daily micturition frequency. In a subset formal psychophysical testing of thermal and ischemic pain was performed at 2 times of the menstrual cycle, corresponding to the luteal and follicular phases. Cystometrograms were performed at the same time. RESULTS: Subjects with IC had higher pain scores and frequency than controls throughout the entire menstrual cycle. Pain scores were highest in the perimenstrual period in subjects with IC and controls. Micturition frequency was highest in the perimenstrual period in subjects with IC. Cystometric evaluation of a first need to void and the evocation of bladder pain demonstrated that lower intravesical volume and pressure were necessary to evoke bladder pain during the follicular period than during the luteal period in subjects with IC, although there was no effect on the first need to void. CONCLUSIONS: These findings are consistent with clinical lore that suggests a perimenstrual flare in pain in subjects with IC. To our knowledge it also demonstrates for the first time a menstrual cycle effect on bladder sensory function in subjects with IC. This suggests a potential role of gonadal hormones on bladder sensory processing and, therefore, a potential role for hormonal modulation as a therapeutic modality in this patient population.
Age Distribution↗
Styles of pain coping predict cardiovascular function following a cold pressor test.
BACKGROUND: While many studies have examined the impact of pain-related coping in adjustment to chronic pain, relatively few have evaluated the physiological consequences of differences in pain-coping styles. OBJECTIVE: The association between strategies for coping with pain and cardiovascular functioning following exposure to painfully cold water was evaluated. METHODS: Impedance cardiography was used to assess cardiovascular functioning in 50 healthy subjects before and after a cold pressor test. RESULTS: The self-reported use of active pain-coping strategies was associated with reductions in mean arterial pressure and cardiac contractility from pre- to post-cold pressor. In contrast, higher levels of pain catastrophizing were related to increases in cardiac contractility following acute cold pain. Importantly, coping variables predicted cardiovascular responses, whereas characteristics of the noxious stimulus (pain tolerance time and pain ratings) did not. CONCLUSIONS: These findings highlight the importance of coping styles in shaping physiological responses to pain and suggest that interventions targeting increases in adaptive coping and decreases in pain catastrophizing may reduce pain's adverse impact.
Adaptation, Psychological↗
What is controlled for in placebo-controlled trials?
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Control Groups↗
Sex-related psychological predictors of baseline pain perception and analgesic responses to pentazocine.
Sex differences in pain perception and analgesic responses have garnered increasing attention in recent years. We examined the association of psychological factors to baseline pain perception and pentazocine analgesia among 49 healthy women and 39 men. Subjects completed psychological questionnaires measuring positive and negative affect as well as catastrophizing. Subsequently, responses to experimental pain were assessed before and after double-blind administration of intravenous pentazocine (0.5mg/kg). In correlational analyses, positive affect predicted lower pain sensitivity among men but not women. Negative affect predicted lower baseline pain tolerances among both sexes but predicted poorer analgesia only among men. Catastrophizing was associated with greater pain sensitivity and less analgesia more consistently in men than women. Regression models revealed that positive affect predicted lower overall pain sensitivity and catastrophizing predicted poorer overall analgesic responses among men, while no significant predictors of overall pain or analgesia emerged for women. Moreover, positive affect and catastrophizing were negatively and positively correlated, respectively, with side effects from the medication, but only among men. These findings indicate sex-dependent associations of psychological factors with baseline pain perception, analgesic responses, and medication side effects.
Adult↗
Sex differences in opioid analgesia: clinical and experimental findings.
Sex differences in analgesic responses to opioids have received increasing attention in recent years. This article examines the literature on sex differences in opioid analgesia, including the results of studies from the authors' own laboratories. In general, nonhuman animal studies suggest more robust opioid analgesic responses in males relative to females; however, the human studies completed to date seem to indicate greater opioid analgesia among females. The most consistent evidence of sex differences in analgesia comes from studies of kappa-agonist-antagonists administered to patients following oral surgery. These data indicate more robust analgesia in females, and dose-response characteristics suggest that these agents possess both analgesic and antianalgesic properties, and the agonists may produce these effects in different proportions for women versus men. In contrast, the data from laboratory pain models in humans suggest greater analgesic effects in women in response mu-opioid agonists but not kappa-agonist-antagonists. Multiple mechanisms may explain sex differences in opioid analgesia, including gonadal hormonal effects, pharmacokinetics and pharmacodynamics, genetic influences, balance of analgesic/antianalgesic processes, and psychological factors. However, the disparity of results obtained from different pain models--animals versus humans and clinical pain versus experimental pain in humans--suggests that the models themselves are mechanistically different. Additional investigation is warranted in order to further explicate the nature of sex differences in opioid analgesia and to elucidate the underlying mechanisms.
Analgesics, Opioid↗
Influences of gender role and anxiety on sex differences in temporal summation of pain.
UNLABELLED: Previous research has consistently shown moderate to large differences between pain reports of men and women undergoing experimental pain testing. These differences have been shown for a variety of types of stimulation. However, only recently have sex differences been demonstrated for temporal summation of second pain. This study examined sex differences in response to temporal summation of second pain elicited by thermal stimulation of the skin. The relative influences of state anxiety and gender role expectations on temporal summation were investigated. Asymptomatic undergraduates (37 women and 30 men) underwent thermal testing of the thenar surface of the hand in a temporal summation protocol. Our results replicated those of Fillingim et al indicating that women showed increased temporal summation compared to men. We extended those findings to demonstrate that temporal summation is influenced by anxiety and gender role stereotypes about pain responding. When anxiety and gender role stereotypes are taken into account, sex is no longer a significant predictor of temporal summation. These findings highlight the contribution of social learning factors in the differences between sexes' pain perception. PERSPECTIVE: Results of this study demonstrate that psychosocial variables influence pain mechanisms. Temporal summation was related to gender role expectations of pain and anxiety. These variables explain a significant portion of the differences between men and women's pain processing, and may be related to differences in clinical presentation.
Adolescent↗
Catastrophizing predicts changes in thermal pain responses after resolution of acute dental pain.
UNLABELLED: Substantial research suggests that coping strategies, especially catastrophizing, play an important role in shaping adjustment to chronic pain. Although laboratory and clinical studies both suggest that catastrophizing enhances pain, the interaction of catastrophizing and clinical pain on pain sensitivity has received little attention. The present study evaluated the extent to which catastrophizing influenced laboratory thermal pain responses during and after the resolution of acute dental pain. Thermal pain threshold and tolerance, as well as self-reported catastrophizing, were determined in 46 dental patients (15 men and 31 women) experiencing pain as a result of acute pulpitis. All subjects participated in 2 experimental sessions; the first took place immediately before endodontic treatment for relief of pulpal pain, and the second session occurred when patients were pain free, approximately 1 to 2 weeks later. Thermal pain thresholds increased on resolution of acute dental pain, whereas levels of catastrophizing did not change from pretreatment to post-treatment. Catastrophizing was unrelated to thermal pain responses in the presence of acute dental pain (ie, during the first session). Once patients were pain free, catastrophizing showed significant inverse associations with measures of thermal pain threshold and tolerance. In addition, catastrophizing was a robust predictor of changes in thermal pain responses across sessions, with higher baseline catastrophizing predicting reductions or relatively smaller increases in pain threshold and tolerance after successful treatment of acute pain. These data suggest that catastrophizing is prospectively associated with enhanced sensitivity to and reduced tolerance for thermal pain. The use of catastrophizing as a coping strategy might interfere with the resolution of sensitization after cessation of an acutely painful condition, or it might be associated with magnified experimental pain responses across time. PERSPECTIVE: The findings of the present study suggest that, in some instances, different ethnic groups and genders may use the same descriptors to report different levels of pain. In the context of clinical pain assessment, it may be important to consider the possibility that descriptions of painful sensations reflect, in part, demographic characteristics.
Adaptation, Psychological↗
Ethnic differences in pain coping: factor structure of the coping strategies questionnaire and coping strategies questionnaire-revised.
UNLABELLED: Coping has been examined extensively in the pain literature, although coping instruments have been typically validated in clinical populations with little ethnic diversity. This study examined the factor structure of the Coping Strategies Questionnaire (CSQ) and the CSQ-Revised (CSQ-R) in 650 healthy male and female African American (44%) and white (56%) subjects and explored associations of coping to health and pain-related measures. Factor analyses revealed 6 components for each ethnic group, accounting for comparable amounts of variance and resembling previously reported CSQ subscales. Internal consistency for both ethnic groups was acceptable (0.72-0.91). There were significant main effects for ethnicity on 4 of the CSQ-R scales (P < .05). No ethnic differences in pain or health variables emerged, although when split into high-pain versus minimal-pain groups, differences were revealed on catastrophizing. Results indicate that the factor structure of the CSQ-R in healthy adults is similar to clinical populations and is comparable across African American and white subjects. Group differences on CSQ-R scales suggest potentially important ethnic influences on pain coping. These findings support the use of the CSQ-R to assess coping in African Americans and in healthy young adults. Additional clinical research is needed to determine the practical importance of group differences in pain coping. PERSPECTIVE: Coping has been examined extensively in the pain literature, although coping instruments typically have been validated in clinical populations with little ethnic diversity. This study examines the factor structure of the CSQ-Revised in an ethnically diverse population and supports the use of the CSQ-R to assess coping in African Americans and in healthy young adults.
Adaptation, Psychological↗
Sex differences in responses to epidural steroid injection for low back pain.
UNLABELLED: Sex differences in clinical and experimental pain responses have been widely reported; however, few studies have examined sex differences in outcomes from interventional pain treatment and the predictors thereof. The aims of this study were to examine sex differences in (1) the acute pain produced by epidural steroid injections (ESIs), (2) clinical improvements in pain and pain-related psychological distress and disability after ESIs, and (3) predictors of the clinical response to ESIs. A total of 57 patients (37 menopausal women and 20 men), seen in the pain clinic of a regional medical center for ESI therapy, participated. Patients rated the painfulness of the ESI procedure itself. Also, clinical pain, depression, and disability were assessed before treatment and at 2 weeks and 2 months after the ESIs. Participants also were queried about their expectations of successful pain relief, coping strategies, and pain-related anxiety, which were examined as predictors of treatment outcome. Men reported significantly greater pain intensity and unpleasantness than women for the first injection only. All groups showed significant reductions in clinical pain, depression, and disability at 2 weeks compared to baseline, but minimal change occurred between 2 weeks and 2 months past baseline. No sex differences in the magnitude of treatment response emerged; however, specific dimensions of pain coping were associated with treatment responses in a sex-dependent manner. These findings suggest that the determinants of ESI pain and treatment outcome might differ across sex. PERSPECTIVE: Sex-related influences on pain responses have been widely reported, but few studies have explored sex-dependent predictors of treatment response. These findings indicate that pain coping was differentially associated with outcomes after ESI in women versus men.
Adaptation, Psychological↗
Catastrophizing as a mediator of sex differences in pain: differential effects for daily pain versus laboratory-induced pain.
Sex differences in the experience of pain have been widely reported, with females generally reporting more frequent clinical pain and demonstrating greater pain sensitivity. However, the mechanisms underpinning such differences, while subject to intense speculation, are not well-characterized. Catastrophizing is a cognitive and affective process that relates strongly to enhanced reports of pain and that varies as a function of sex. It is thus a prime candidate to explain sex differences; indeed, several prior studies offer evidence that controlling for catastrophizing eliminates the gap between men and women in reported pain. We recruited 198 healthy young adults (115 female) who took part in laboratory studies of pain responses, including thermal pain, cold pain, and ischemic pain, and who also completed questionnaires assessing catastrophizing, mood, and day-to-day painful symptoms (e.g. headache, backache). Women reported greater levels of catastrophizing, more recent painful symptoms, and demonstrated lower pain thresholds and tolerances for noxious heat and cold relative to men. Mediational analyses suggested that after controlling for negative mood, catastrophizing mediated the sex difference in recent daily pain but did not mediate the much larger sex differences in pain threshold and tolerance. These findings highlight the role of catastrophizing in shaping pain responses, as well as illuminating potentially important differences between experimental pain assessment and the clinical experience of pain.
Adaptation, Psychological↗
Experimental pain models reveal no sex differences in pentazocine analgesia in humans.
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 kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-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.
Adolescent↗
Endogenous opioids, blood pressure, and diffuse noxious inhibitory controls: a preliminary study.
A 2003 study suggested that there are age differences in diffuse noxious inhibitory controls (DNIC), a form of endogenous pain inhibition. The present report describes a followup study employing a pharmacological blockade of endogenous opioids, i.e., using naloxone, in a small subset (n=6) of healthy young volunteers to characterize the opioid-dependence of DNIC, as well as DNIC's association with cardiovascular reactivity. Findings suggested that, while opioid blockade enhanced cardiovascular reactivity to cold pain, DNIC was not affected by administering naloxone. Interestingly, greater cardiovascular responses to noxious cold were associated with enhanced DNIC in this small sample. This relationship, which did not appear opioid-dependent, supports previous models integrating cardiovascular activity with the functioning of pain-modulatory systems.
Adult↗
The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans.
Sex specificity of neural mechanisms modulating nociceptive information has been demonstrated in rodents, and these qualitative sex differences appear to be relevant to analgesia from kappa-opioid receptor agonists, a drug class reported to be clinically effective only in women. Via quantitative trait locus mapping followed by a candidate gene strategy using both mutant mice and pharmacological tools, we now demonstrate that the melanocortin-1 receptor (Mc1r) gene mediates kappa-opioid analgesia in female mice only. This finding suggested that individuals with variants of the human MC1R gene, associated in our species with red hair and fair skin, might also display altered kappa-opioid analgesia. We found that women with two variant MC1R alleles displayed significantly greater analgesia from the kappa-opioid, pentazocine, than all other groups. This study demonstrates an unexpected role for the MC1R gene, verifies that pain modulation in the two sexes involves neurochemically distinct substrates, and represents an example of a direct translation of a pharmacogenetic finding from mouse to human.
Adolescent↗
Clinical characteristics of chronic back pain as a function of gender and oral opioid use.
STUDY DESIGN: A cross-sectional analysis of data derived from patients with chronic spinal pain undergoing evaluation at a multidisciplinary pain treatment center was conducted. OBJECTIVE: To determine whether pain severity, psychological status, and physical disability differed as a function of gender and opioid use, and whether the clinical correlates of opioid use differed in women and men with chronic back pain. SUMMARY OF BACKGROUND DATA: Gender differences in the experience of pain have been widely reported. For example, in the general population, several chronic pain conditions are more prevalent among women than among men, and many experimental studies demonstrate lower pain thresholds and tolerances among women. In addition, recent evidence from studies of experimental and acute clinical pain suggests that responses to analgesic medications may differ in women and men. METHODS: The sample consisted of 240 patients (35% women) with low back, upper back, or neck pain undergoing evaluation for treatment at a multidisciplinary pain center. The patients were classified as opioid or nonopioid users on the basis of self-report and medical record review. All the patients completed a battery of clinical assessments, including measures of pain severity, psychological adjustment, self-reported disability, functional tasks, and pain tolerance. Analyses were conducted to examine clinical variables as a function of gender and opioid use. RESULTS: The results indicated that opioid use was associated with greater self-reported disability and poorer function in both women and men. However, the association of opioid use with affective distress differed between women and men. The women using opioids showed lower affective distress, whereas the opioid-using men reported greater affective distress. Opioid use was not associated with pain severity, although the women reported greater pain than men. CONCLUSIONS: These findings indicate that both opioid use and gender are significant predictors of clinical status of patients with chronic spinal pain. More interesting, these two variables interact because opioid use was associated with increased affective distress among the men, but the reverse was true for the women. In addition, the women reported greater pain severity, which is consistent with some previous findings. Potential explanations for these findings are presented, and the practical implications are discussed.
Administration, Oral↗
Pain tolerance as a predictor of outcome following multidisciplinary treatment for chronic pain: differential effects as a function of sex.
Sex-related differences in the experience of clinical and experimental pain have been widely reported. Females are at elevated risk for developing several chronic pain conditions and women demonstrate greater sensitivity to noxious stimulation in the laboratory. However, relationships between responses to experimental noxious stimuli and the experience of clinical pain have not been well characterized. One previous study of healthy adults indicated that pain threshold and tolerance were associated with clinical pain among women but not men (i.e. females with lower pain threshold and tolerance reported more clinical pain). In the present investigation, relationships between pain tolerance and outcomes of treatment for chronic pain were evaluated in a sex-dependent manner. Ischemic pain tolerance was assessed prior to treatment in 171 chronic pain patients completing a pain management program. Outcomes were measured as changes in pain severity, affect, and pain-related disability. Over the course of treatment, women demonstrated greater improvement in pain-related disability while men showed more reduction in pain. Ischemic pain tolerance was related to outcome in a sex-specific fashion. Women with higher pain tolerances showed greater improvement in pain, more reduction in pain-related interference, and more increases in activity level than women with lower pain tolerances. In contrast, pain tolerance was not associated with positive treatment outcomes among men. These results indicate that experimental pain responses may be most clinically relevant for women, and that sex differences may exist in the determinants of pain-treatment outcomes.
Adult↗