Biomedical subjects

R B Fillingim

Publications and source records attributed to R B Fillingim.

At least 19 recordsLinked to original sources

PubMed2005

Melanocortin-1 receptor gene variants affect pain and mu-opioid analgesia in mice and humans.

BACKGROUND: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on kappa-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant mu-opioid receptor. OBJECTIVE: To characterise sensitivity to pain and mu-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. METHODS: Comparisons of spontaneous mutant C57BL/6-Mc1r(e/e) mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. RESULTS: C57BL/6-Mc1r(e/e) mutant mice and human redheads--both with non-functional MC1Rs--display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the mu-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. CONCLUSIONS: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics.

Adolescent↗

PubMed2002

Sex differences in analgesic responses: evidence from experimental pain models.

BACKGROUND AND OBJECTIVE: Sex-related influences on the experience of pain have received considerable empirical attention. Women are at greater risk for several forms of clinical pain and exhibit greater perceptual responses to experimental pain. In recent years, investigators have turned their attention to the influence of sex-related factors on analgesic responses. The purpose of this review is to examine the literature on sex differences in analgesic responses, emphasizing findings from experimental studies. METHODS: First, important methodological issues in laboratory pain research are presented, and sex differences in responses to experimentally-induced pain are briefly addressed. Next, previous data from non-human animal research and human experimental and clinical research related to sex differences in analgesia are discussed. Also, preliminary results are presented from an ongoing study in our laboratory examining analgesic responses in women and men. RESULTS AND CONCLUSIONS: Both previous research and preliminary findings from our laboratory suggests that opioids produce greater analgesic responses in women than men. Potential mechanisms underlying sex differences in analgesia are proposed, and important directions for future research are suggested.

Analgesics↗

PubMed2001

The association of hormone replacement therapy with experimental pain responses in postmenopausal women.

Considerable experimental research suggests that ovarian hormones can influence pain perception, and recent epidemiologic and clinical research suggests that exogenous hormone use may influence the prevalence and severity of clinical pain among women. However, to date no studies have examined the influence of hormone replacement therapy (HRT) on experimental pain responses and recent pain complaints among postmenopausal women. In this study, self-reported recent pain and general health were obtained, and thermal pain responses were assessed in three groups of healthy older adults: (1) women on HRT, (2) women not on HRT (No-HRT), and (3) men. Results indicated no group differences in recent pain complaints or self-reported health, but differences emerged for measures of thermal pain perception. Specifically, HRT women showed lower pain thresholds and tolerances than No-HRT women and men, and the latter two groups did not differ from each other. The potential explanations and limitations of the observed findings are discussed.

Aged↗

PubMed2001

Gender role expectations of pain: relationship to sex differences in pain.

Empirical research supports the existence of sex differences in pain; yet these differences are poorly understood. Although biological mechanisms have been posited to explain variability, results of pain modeling manipulations suggest social learning may be a stronger influence on pain response. In this report we use the term sex to refer to the biological category of male or female. We use the term gender to refer to the socially acquired aspects of being male or female sometimes referred to as femininity and masculinity. This study investigated a new measure, the Gender Role Expectations of Pain questionnaire (GREP), which was designed to measure sex-related stereotypic attributions of pain sensitivity, endurance, and willingness to report pain. Subjects were 156 male and 235 female undergraduates at a southeastern university. Psychometric investigation of the questionnaire revealed a 5-factor solution that closely mirrored the theoretical construction of the items. Test-retest reliability was also shown for individual items on a separate sample of 28 subjects. Results supported hypotheses about gender role: both men and women rated men as less willing to report pain than women (F(1,389) = 336, P <.001); both men and women rated women more sensitive (F(1,389) = 9.5, P <.05) and less enduring of pain (F(1,389) = 65.7, P <.001) than men; and men rated their own endurance as higher than the typical man (F(1,389) = 65.7, P <.001). Sex accounted for 46% of the variance in willingness to report pain. Results suggest that the GREP distinguished between the socially learned reactions to pain for men and women. It is recommended that the influence of gender-related expectations for pain be assessed in all studies investigating human sex differences in pain.

Journal Article↗

PubMed2001

Effects of age on temporal summation and habituation of thermal pain: clinical relevance in healthy older and younger adults.

Although the effects of aging on the experience of clinical pain seem relatively clear, investigations of age-related changes in pain perception using laboratory-based pain assessment procedures have yielded contradictory findings. One potential source of variability in this literature is the type of experimental noxious stimulus that is used. Although thermal pain thresholds are the most commonly reported measure of pain sensitivity, use of suprathreshold stimuli in pain assessment procedures may yield additional, more clinically relevant information concerning the effects of aging on the experience of pain. The present study examined the effects of age on temporal summation of both the intensity and unpleasantness of thermal pain at multiple stimulus temperatures. Specifically, responses to repetitive thermal stimuli delivered to the volar forearm at 47 degrees C, 50 degrees C, and 53 degrees C were assessed in 34 younger (mean age, 22.4 years) and 34 older (mean age, 62.2 years) healthy volunteers. Results suggested that for the 47 degrees C and 50 degrees C stimulus trains, older adults exhibited higher ratings of the intensity and unpleasantness of thermal pain and enhanced temporal summation of thermal pain relative to younger adults. Moreover, thermal pain sensitivity was inversely related to perceptions of general health and to reports of recent clinical pain among younger, but not older, subjects. Collectively these findings may indicate small, although potentially significant, age-related alterations in the plasticity of the central nervous system or endogenous pain-modulatory capacities.

Journal Article↗

PubMed2001

Age-associated differences in responses to noxious stimuli.

BACKGROUND: Although population-based studies typically report age-associated increases in clinical pain, laboratory-based pain assessment procedures generally indicate diminished pain sensitivity with age. The majority of these studies have utilized noxious thermal stimuli as the method of pain induction. However, other pain assessment methodologies, including ischemic pain induction, may have a more meaningful relationship to clinical pain. The present study examined the effects of age on responses to a variety of experimental noxious stimuli. In addition, relationships between cardiovascular measures and pain responses were investigated in both older and younger subjects. METHODS: Responses to thermal, mechanical, and ischemic pain were assessed in 34 younger (mean age, 22.4 years) and 34 older adults (mean age, 62.2 years). In addition, relationships between resting blood pressure and pain responses were assessed separately for older and younger participants. RESULTS: Although group differences in thermal and mechanical pain responses did not achieve statistical significance, older individuals demonstrated substantially lower ischemic pain thresholds and tolerances assessed via the modified submaximal effort tourniquet procedure (ps < .01). Overall, higher resting arterial blood pressures were associated with increased pain thresholds and tolerances, although relationships between blood pressure and ischemic pain variables were evident only for the younger group. CONCLUSIONS: These findings indicate that age-related differences in responses to experimental noxious stimuli vary as a function of the pain induction task, with older individuals showing greater sensitivity to clinically relevant stimuli. In addition, the absence of a relationship between blood pressure and ischemic pain responses in older adults may suggest potential functional decrements in at least one endogenous pain-modulatory system.

Adult↗

PubMed2000

Sex, gender, and pain: women and men really are different.

Sex-related differences in the experience of both clinical and experimentally induced pain have been widely reported. Specifically, females are at greater risk for developing several chronic pain disorders, and women exhibit greater sensitivity to noxious stimuli in the laboratory compared with men. Several mechanisms have been proposed to account for these sex differences. Psychosocial factors such as sex role beliefs, pain coping strategies, mood, and pain-related expectancies may underlie these effects. In addition, there is evidence that familial factors can alter pain responses, and these intergenerational influences may differ as a function of sex. Sex hormones are also known to affect pain responses, which may mediate the sex differences. Although the magnitude of these effects has not been well characterized, there are potentially important practical implications of sex differences in pain responses. These implications are discussed, and directions for future research are delineated.

Adaptation, Psychological↗

PubMed2000

Sex-related hormonal influences on pain and analgesic responses.

Considerable evidence indicates sex-related differences in pain responses and in the effectiveness of various analgesic agents. Specifically, females are at greater risk for experiencing many forms of clinical pain and are more sensitive to experimentally induced pain relative to males. Regarding analgesic responses, nonhuman animal studies indicate greater opioid analgesia for males, while a limited human literature suggests the opposite. Though the mechanisms underlying these effects remain unclear, the influence of gonadal hormones on nociceptive processing represents one plausible pathway whereby such sex differences could emerge. The present article reviews the complex literature concerning sex steroid effects on pain responses and analgesia. First, nonhuman animal research related to hormonal effects on nociceptive sensitivity and analgesic responses is presented. Next, human studies regarding gonadal hormonal influences on experimental pain responses are reviewed. Several potential mechanisms underlying hormonal effects on nociceptive processing are discussed, including hormonal effects to both peripheral and central nervous system pathways involved in pain transmission. Finally, based on these findings we draw several conclusions and make specific recommendations that will guide future research as it attempts to elucidate the magnitude and importance of sex-related hormonal effects on the experience of pain.

Analgesics↗

PubMed2000

Low intensity vagal nerve stimulation lowers human thermal pain thresholds.

The effect of vagal nerve stimulation (VNS) on thermal pain sensation was studied in eight subjects who had vagal nerve stimulators surgically implanted for purposes of seizure control. Prior to their involvement in the study, all subjects had the intensity of their VNS (30 Hz, 0.5 ms, 1.0-2.75 mA) adjusted upwards until achieving their desired clinical effect of reduced seizures. Thermal pain thresholds were determined using a Medoc TSA-2001 with a thermode applied to the skin of the forearm. During VNS at settings 100% of those used clinically to control their seizures, subjects showed a statistically significant decrease in their thermal pain threshold of 1.1+/-0.4 degrees C. Acute effects of graded VNS on thermal pain thresholds were determined in seven of the subjects after cessation of chronic VNS. Two thermal threshold measurements were obtained while the subject received sham stimulation (0 mA intensity), during tactile control stimulation and during 30 s of VNS at intensities approximately 33, 66 and 100% of the settings utilized to control their seizures. Tactile control stimulation was provided by electrical stimulation of the skin of the ankle with the intensity adjusted by the patient to match the intensity of any sensations felt in the neck during VNS. Subjects were not aware of the settings employed. Their stimulator was adjusted with each trial and an ascending/descending ordering of intensity was utilized with an inter-trial interval of 2 min. Thermal pain thresholds were significantly decreased in relation to tactile control stimulation at all intensities of VNS tested with the greatest effect occurring at the 66% level. Subjects were also monitored non-invasively and hemodynamic responses to VNS were determined. No significant alterations in hemodynamic variables were observed. The findings of this human study are consistent with experiments in non-human animals which demonstrate a pro-nociceptive effect of low intensity VNS.

Adolescent↗

PubMed2000

Sex-dependent effects of reported familial pain history on recent pain complaints and experimental pain responses.

Previous research has demonstrated that both sex and familial pain history can influence clinical pain, and sex is known to affect experimental pain responses. However, the potential interactive effects of sex and family history on pain-related symptoms and experimental pain have not been investigated. This experiment examined recent pain complaints and laboratory pain responses as a function of sex and reported family history of pain in 212 (122 female, 90 male) young adults. All subjects completed questionnaires regarding family history of pain, recent pain experiences, and psychological measures of hypervigilance. Then, warmth detection thresholds, heat pain thresholds and heat pain tolerances were determined. Results revealed sex-dependent influences of familial pain history on recent pain complaints and experimental pain responses. Specifically, a positive family history of pain was associated with increased reports of pain over the previous month and poorer general health as well as enhanced sensitivity to thermal stimuli among females but not males. Higher levels of hypervigilance accounted for some of the family history effects on recent pain complaints but not experimental pain measures. Potential mechanisms underlying these effects of family history among females are discussed.

Adult↗

PubMed1999

Sex differences in heat pain thresholds as a function of assessment method and rate of rise.

Studies of sex differences in the responses to experimentally induced pain demonstrate greater pain sensitivity among females than males. However, studies investigating heat pain responses have produced inconsistent results. Differences in stimulus characteristics and assessment methods probably account for this variability. This study examined sex differences in the heat pain threshold as a function of two different assessment methods and varying rates of rise. Nineteen female and 18 male healthy volunteers underwent heat pain threshold assessment via the method of levels and the method of limits. In addition, both fast (4.0 degrees C/s) and slow (0.5 degrees C/s) rates of rise were used for the method of levels assessments. In order to examine the reliability of threshold values, each subject participated in two sessions, separated by approximately 8 days. Females evinced lower thresholds than males for the method of levels assessments with both slow and fast rates of rise (ps < 0.05), while no sex differences emerged for the threshold assessed via the method of limits. Test-retest reliability coefficients were relatively high. However, thresholds generally increased significantly from session 1 to session 2. Between method correlations were generally low to moderate. These findings indicate that the method of levels may be more sensitive to sex differences than the more commonly used method of limits. Also, thresholds appear to increase from session 1 to session 2, and thresholds assessed via different methods are not strongly correlated. Potential implications of these results for experimental pain assessment are discussed.

Adult↗

PubMed1999

Self-reported abuse history and pain complaints among young adults.

OBJECTIVE: Considerable evidence suggests that a self-reported history of physical and/or sexual abuse is more frequently reported among chronic pain populations and is associated with poorer adjustment to pain. However, previous research has typically included patients seeking treatment for pain, whereas few population-based studies have explored the association between abuse history and pain. This purpose of this study was to examine the association between self-reported history of sexual or physical abuse and recent pain complaints, health-related variables, and psychological disturbance among a nonclinical sample of young adults. DESIGN: Subjects were 426 (275 female, 151 male) college students who completed a series of questionnaires assessing abuse history, recent pain, health care utilization, perceived health, and psychological variables. RESULTS: Females reported a positive history of abuse (PHA) more frequently than males (43.5% vs. 23.8%), and females reported significantly higher rates for all types of abuse except physical abuse during childhood (p < 0.05). PHA subjects reported experiencing pain in more sites and pain of higher severity over the past month compared to subjects with a negative history of abuse (NHA) (p < 0.05). PHA subjects also reported more health care utilization and greater psychological disturbance, including depression, somatization, negative temperament, and higher levels of catastrophizing (p < 0.05). Interestingly, when somatization and depression scale scores were used as covariates, group differences in pain complaints and health care utilization became nonsignificant (p > 0.10). CONCLUSION: These findings suggest that a self-reported history of physical or sexual abuse is associated with increased pain complaints, health care utilization, and psychological disturbance even among young adults from a nonclinical population. Moreover, the association between abuse and pain complaints appears to be moderated at least in part by the higher levels of somatization and depression observed in the PHA group.

Adolescent↗

PubMed1999

Effects of gender and acute dental pain on thermal pain responses.

OBJECTIVE: Considerable research suggests that females exhibit greater sensitivity to laboratory pain procedures than do males; however, whether the presence of acute clinical pain influences this sex difference in pain sensitivity has not been investigated. The present experiment investigated the effects of sex and acute dental pain on laboratory pain responses. DESIGN: Thermal pain onset and tolerance were determined in 46 dental patients (15 male, 31 female) experiencing pain due to acute irreversible pulpitis and in 33 healthy controls (13 male, 20 female). In addition, measures of mood and coping were obtained in all participants. All subjects participated in two experimental sessions. The first session took place immediately before the patients underwent endodontic treatment for relief of pulpal pain. The second session took place approximately 1-2 weeks later, when pulpitis patients were pain free after treatment. During each session, thermal pain onset and tolerance were assessed with a 1-cm2 contact thermode applied to the right volar forearm using an ascending method of limits. RESULTS: During both sessions, thermal pain onset and tolerance were lower in control females than in control males; however, male and female pulpitis patients did not differ in their thermal pain responses during either session. Pulpitis patients also showed greater affective distress than controls. CONCLUSIONS: These data suggest that the sex difference in thermal pain sensitivity frequently reported in pain-free subjects appears to be absent in patients presenting with acute dental pain. However, this effect cannot be explained solely based on the presence of clinical pain because the effect on pain threshold and tolerance persisted into session 2, when pulpitis patients were pain free. Potential explanations for these results are discussed.

Acute Disease↗

PubMed1998

Resting blood pressure and thermal pain responses among females: effects on pain unpleasantness but not pain intensity.

In order to investigate the influence of resting blood pressure on thermal pain responses among females, this experiment studied 21 pain-free, normotensive females (mean age 23) classified as having high (HBP) vs. low blood pressure (LBP) based on a median split of resting blood pressure collected prior to thermal testing. All subjects then underwent thermal pain testing, including determination of pain threshold and tolerance followed by verbal descriptor ratings of the intensity and unpleasantness of suprathreshold thermal stimuli, ranging from 45 to 49 degrees C. Thermal stimuli were delivered to the volar forearm and the ipsilateral face using a 1 cm2 contact thermode. Results indicated that the blood pressure groups did not differ in thermal pain threshold or tolerance or on ratings of the intensity of suprathreshold thermal stimuli. However, the HBP group provided significantly lower ratings of thermal pain unpleasantness than the LBP group (P < 0.01). These data indicate that resting blood pressure is inversely associated with pain sensitivity among females, but this relationship may be selective for the affective component of pain.

Adolescent↗

PubMed1998

Sex differences in the perception of noxious experimental stimuli: a meta-analysis.

Fillingim and Maixner (Fillingim, R.B. and Maixner, W., Pain Forum, 4(4) (1995) 209-221) recently reviewed the body of literature examining possible sex differences in responses to experimentally induced noxious stimulation. Using a 'box score' methodology, they concluded the literature supports sex differences in response to noxious stimuli, with females displaying greater sensitivity. However, Berkley (Berkley, K.J., Pain Forum, 4(4) (1995) 225-227) suggested the failure of a number of studies to reach statistical significance suggests the effect may be small and of little practical significance. This study used meta-analytic methodology to provide quantitative evidence to address the question of the magnitude of these sex differences in response to experimentally induced pain. We found the effect size to range from large to moderate, depending on whether threshold or tolerance were measured and which method of stimulus administration was used. The values for pressure pain and electrical stimulation, for both threshold and tolerance measures, were the largest. For studies employing a threshold measure, the effect for thermal pain was smaller and more variable. The failures to reject the null hypothesis in a number of these studies appear to have been a function of lack of power from an insufficient number of subjects. Given the estimated effect size of 0.55 threshold or 0.57 for tolerance, 41 subjects per group are necessary to provide adequate power (0.70) to test for this difference. Of the 34 studies reviewed by Fillingim and Maixner, only seven were conducted with groups of this magnitude. The results of this study compels to caution authors to obtain adequate sample sizes and hope that this meta-analytic review can aid in the determination of sample size for future studies.

Female↗

PubMed1998

A psychophysical study of discomfort produced by repeated filling of the urinary bladder.

Psychophysical studies were performed in 10 healthy, female volunteers using urinary bladder distension (UBD) as a visceral stimulus. Stimulus methodology was similar to that used clinically for obtaining cystometrograms with a fixed-rate (100 cc/min normal saline) filling of the urinary bladder, occasional pauses and simultaneous measure of bladder pressure using a catheter-transducer assembly. During bladder filling, subjects were asked to report sensations by verbal report and by using an electronic, hand-held, visual-analog-scale device. Sensations evoked by UBD were generally localized to the suprapubic region. UBD produced cardiovascular responses which increased with repeated trials. Sensation intensity increased with repeated UBDs as indicated by global pain ratings. Intravesical pressure and volume correlated with sensation intensity. The volume of distending fluid needed to produce a report of discomfort was highly variable from trial to trial and did not change significantly with repeated UBDs. The intravesical pressure which produced a report of discomfort was less variable and significantly decreased with repeated UBDs. The change in intravesical pressure and volume needed to produce discomfort was inversely correlated with initial intravesical pressure measures. Similar to findings in other organ systems, these findings demonstrate that repeated presentations of a visceral stimulus may lead to an increase in physiological and perceptual responses to pain.

Adult↗

PubMed1997

Menstrual cycle, blood pressure and ischemic pain sensitivity in women: a preliminary investigation.

Eleven women were tested twice for ischemic pain sensitivity; once during their follicular phase (Days 4-9) and once during their mid-late luteal phase (5-10 days after ovulation) of a confirmed ovulatory cycle. Additionally, in order to examine blood pressure-related hypoalgesic effects, each had 3-4 clinic blood pressures determined during an initial screening interview and each also completed a daily symptom calendar for one complete menstrual cycle prior to testing in order to investigate relationships between 'real life' symptomatology and laboratory-induced pain sensitivity. Results revealed significantly shorter pain tolerance times and marginally shorter pain threshold times in the luteal vs. follicular phase, while verbal descriptors of pain intensity (sensory) and pain unpleasantness (affective) did not vary with cycle phase. Clinic blood pressures were positively correlated with pain threshold and tolerance times assessed during both cycle phases. Real-life physical symptom ratings were predictive of laboratory pain intensity ratings during the follicular phase and tended to predict unpleasantness ratings during both phases. These results not only confirm recent reports of greater sensitivity to ischemic pain in women during the luteal phase of their cycle, but extend the literature by demonstrating pressure-related hypoalgesic effects in women during both cycle phases.

Adult↗

PubMed1997

Sexual and physical abuse history in subjects with temporomandibular disorders: relationship to clinical variables, pain sensitivity, and psychologic factors.

Recent evidence suggests that a past history of physical and/or sexual abuse is more frequently reported among chronic pain populations; however, the prevalence of reported abuse has not been examined in patients with chronic orofacial pain caused by temporomandibular disorders (TMD). This study compares reported physical/sexual abuse among female TMD subjects recruited from the general population with that of age-matched female control subjects. The association of reported abuse with clinical pain, experimental pain responses, and psychologic variables was examined in the TMD group. Results indicated that a slightly but not statistically greater percentage of TMD subjects (44.8%) reported a history of sexual or physical abuse compared to control subjects (33.3%). Reported abuse among TMD subjects was not related to clinical pain or psychologic variables. Regarding experimental pain responses, TMD subjects reporting a history of abuse exhibited longer ischemic pain tolerances compared to those not reporting abuse; however, the groups did not differ on other experimental pain measures. Results indicate that the reported prevalence of physical/sexual abuse is similar among TMD subjects compared to other chronic pain populations; however, the relationship of abuse to clinical and psychosocial variables remains unclear.

Adolescent↗