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Biomedical subjects

Roger B Fillingim

Publications and source records attributed to Roger B Fillingim.

At least 19 recordsLinked to original sources
PubMed2007

Overview of orofacial pain: epidemiology and gender differences in orofacial pain.

Chronic orofacial pain is a prevalent problem that encompasses numerous disorders with diverse causes and presenting symptoms. Compared with men, women of reproductive age seek treatment for orofacial pain conditions, as well as other chronic pain disorders more frequently. Important issues have been raised regarding gender and sex differences in genetic, neurophysiologic, and psychosocial aspects of pain sensitivity and analgesia. Efforts to improve our understanding of qualitative sex differences in pain modulation signify a promising step toward developing more tailored approaches to pain management.

Analgesia↗
PubMed2007

Sex and pain-related psychological variables are associated with thermal pain sensitivity for patients with chronic low back pain.

UNLABELLED: Biologic and psychological associations with evoked pain sensitivity have been extensively studied in healthy subjects but not among subjects with clinical pain syndromes. This study involved patients with chronic low back pain and investigated whether: 1) sex differences existed for thermal pain sensitivity; and 2) sex, fear-avoidance beliefs, and/or pain catastrophizing influenced thermal pain sensitivity. Thirty-three consecutive patients enrolled in a pain rehabilitation program completed self-report questionnaires and underwent quantitative sensory testing with an established protocol for thermal stimuli. Women had elevated pain sensitivity for measures of tolerance and temporal summation but not for first pulse response. In the multivariate models predicting thermal pain sensitivity, sex was associated with tolerance, and fear-avoidance beliefs were associated with first pulse response. Sex and pain catastrophizing were associated with temporal summation of thermal pain. Future studies involving clinical samples are necessary to replicate these findings and to explore the involvement of cortical structures. PERSPECTIVE: This study suggests that sex, fear-avoidance beliefs, and pain catastrophizing were associated with thermal pain sensitivity for patients with chronic low back pain. These results corroborated sex differences in tolerance and temporal summation observed in the experimental pain literature for healthy subjects. These results also suggest the potential for these specific pain-related beliefs to be associated with a sensitized state because previous studies have demonstrated their association to clinical pain reports, and this study demonstrated associations with thermal pain sensitivity.

Adolescent↗
PubMed2007

An interdisciplinary expert consensus statement on assessment of pain in older persons.

This paper represents an expert-based consensus statement on pain assessment among older adults. It is intended to provide recommendations that will be useful for both researchers and clinicians. Contributors were identified based on literature prominence and with the aim of achieving a broad representation of disciplines. Recommendations are provided regarding the physical examination and the assessment of pain using self-report and observational methods (suitable for seniors with dementia). In addition, recommendations are provided regarding the assessment of the physical and emotional functioning of older adults experiencing pain. The literature underlying the consensus recommendations is reviewed. Multiple revisions led to final reviews of 2 complete drafts before consensus was reached.

Age Factors↗
PubMed2006

Self-reported pain sensitivity: lack of correlation with pain threshold and tolerance.

Many recent studies and several reviews have highlighted the potential clinical applications of experimental pain testing (e.g., for predicting post-surgical pain, treatment responsiveness, etc.). However, the implementation of quantitative sensory testing of pain sensitivity on a broad scale is limited by requirements of time, equipment, and expertise, and their associated costs. One reasonable question is whether one can obtain, via self-report, a valid index of an individual's pain sensitivity and pain tolerance. We analyzed data from a large number of subjects (n=505) who had undergone standardized thermal pain testing, and found that while higher self-reported pain sensitivity was associated with higher scores on a measure of anxiety, no relationship was observed between subjects' self-report of pain sensitivity and subjects' actual pain threshold or tolerance. These findings suggest that circumventing psychophysical pain testing by assessing individuals' self-reported pain sensitivity is unlikely to be a useful strategy.

Adolescent↗
PubMed2006

GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence.

We report that GTP cyclohydrolase (GCH1), the rate-limiting enzyme for tetrahydrobiopterin (BH4) synthesis, is a key modulator of peripheral neuropathic and inflammatory pain. BH4 is an essential cofactor for catecholamine, serotonin and nitric oxide production. After axonal injury, concentrations of BH4 rose in primary sensory neurons, owing to upregulation of GCH1. After peripheral inflammation, BH4 also increased in dorsal root ganglia (DRGs), owing to enhanced GCH1 enzyme activity. Inhibiting this de novo BH4 synthesis in rats attenuated neuropathic and inflammatory pain and prevented nerve injury-evoked excess nitric oxide production in the DRG, whereas administering BH4 intrathecally exacerbated pain. In humans, a haplotype of the GCH1 gene (population frequency 15.4%) was significantly associated with less pain following diskectomy for persistent radicular low back pain. Healthy individuals homozygous for this haplotype exhibited reduced experimental pain sensitivity, and forskolin-stimulated immortalized leukocytes from haplotype carriers upregulated GCH1 less than did controls. BH4 is therefore an intrinsic regulator of pain sensitivity and chronicity, and the GTP cyclohydrolase haplotype is a marker for these traits.

Adult↗
PubMed2006

Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder.

Adrenergic receptor beta(2) (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with a complex array of psychological and physiological phenotypes. These genetic variants should also interact with environmental factors such as physical or emotional stress to produce a phenotype vulnerable to pathological states. In this study, we determined whether common genetic variants of ADRB2 contribute to the development of a common chronic pain condition that is associated with increased levels of psychological distress and low blood pressure, factors which are strongly influenced by the adrenergic system. We genotyped 202 female subjects and examined the relationships between three major ADRB2 haplotypes and psychological factors, resting blood pressure, and the risk of developing a chronic musculoskeletal pain condition-Temporomandibular Joint Disorder (TMD). We propose that the first haplotype codes for lower levels of ADRB2 expression, the second haplotype codes for higher ADRB2 expression, and the third haplotype codes for higher receptor expression and rapid agonist-induced internalization. Individuals who carried one haplotype coding for high and one coding for low ADRB2 expression displayed the highest positive psychological traits, had higher levels of resting arterial pressure, and were about 10 times less likely to develop TMD. Thus, our data suggest that either positive or negative imbalances in ADRB2 function increase the vulnerability to chronic pain conditions such as TMD through different etiological pathways that imply the need for tailored treatment options.

Adolescent↗
PubMed2006

Mental stress provokes ischemia in coronary artery disease subjects without exercise- or adenosine-induced ischemia.

OBJECTIVES: The purpose of this study was to investigate the possibility that some patients with coronary artery disease (CAD) but negative exercise or chemical stress test results might have mental stress-induced ischemia. The study population consisted solely of those with negative test results. BACKGROUND: Mental stress-induced ischemia has been reported in 20% to 70% of CAD subjects with exercise-induced ischemia. Because mechanisms of exercise and mental stress-induced ischemia may differ, we studied whether mental stress would produce ischemia in a proportion of subjects with CAD who have no inducible ischemia with exercise or pharmacologic tests. METHODS: Twenty-one subjects (14 men, 7 women) with a mean age of 67 years and with a documented history of CAD were studied. All subjects had a recent negative nuclear stress test result (exercise or chemical). Subjects completed a speaking task involving role playing a difficult interpersonal situation. A total of 30 mCi 99mTc-sestamibi was injected at one minute into the speech, and imaging was started 40 min later. A resting image obtained within one week was compared with the stress image. Images were analyzed for number and severity of perfusion defects. The summed difference score based on the difference between summed stress and rest scores was calculated. Severity was assessed using a semiquantitative scoring method from zero to four. RESULTS: Six of 21 (29%) subjects demonstrated reversible ischemia (summed difference score > or =3) with mental stress. No subject had chest pain or electrocardiographic changes during the stressor. Mean systolic and diastolic blood pressure and heart rate all increased between resting and times of peak stress. CONCLUSIONS: Mental stress may produce ischemia in some subjects with CAD and negative exercise or chemical nuclear stress test results.

Adenosine↗
PubMed2006

Fear-avoidance beliefs and temporal summation of evoked thermal pain influence self-report of disability in patients with chronic low back pain.

INTRODUCTION: Quantitative sensory testing has demonstrated a promising link between experimentally determined pain sensitivity and clinical pain. However, previous studies of quantitative sensory testing have not routinely considered the important influence of psychological factors on clinical pain. This study investigated whether measures of thermal pain sensitivity (temporal summation, first pulse response, and tolerance) contributed to clinical pain reports for patients with chronic low back pain, after controlling for depression or fear-avoidance beliefs about work. METHOD: Consecutive patients (n=27) with chronic low back pain were recruited from an interdisciplinary pain rehabilitation program in Jacksonville, FL. Patients completed validated self-report questionnaires for depression, fear-avoidance beliefs, clinical pain intensity, and clinical pain related disability. Patients also underwent quantitative sensory testing from previously described protocols to determine thermal pain sensitivity (temporal summation, first pulse response, and tolerance). Hierarchical regression models investigated the contribution of depression and thermal pain sensitivity to clinical pain intensity, and fear-avoidance beliefs and thermal pain sensitivity to clinical pain related disability. RESULTS: None of the measures of thermal pain sensitivity contributed to clinical pain intensity after controlling for depression. Temporal summation of evoked thermal pain significantly contributed to clinical pain disability after controlling for fear-avoidance beliefs about work. CONCLUSION: Measures of thermal pain sensitivity did not contribute to pain intensity, after controlling for depression. Fear-avoidance beliefs about work and temporal summation of evoked thermal pain significantly influenced pain related disability. These factors should be considered as potential outcome predictors for patients with work-related low back pain. SIGNIFICANCE: This study supported the neuromatrix theory of pain for patients with CLBP, as cognitive-evaluative factor contributed to pain perception, and cognitive-evaluative and sensory-discriminative factors uniquely contributed to an action program in response to chronic pain. Future research will determine if a predictive model consisting of fear-avoidance beliefs and temporal summation of evoked thermal pain has predictive validity for determining clinical outcome in rehabilitation or vocational settings.

Avoidance Learning↗
PubMed2006

Placebo analgesia: friend or foe?

The magnitude of placebo analgesia is influenced by environmental and perceptual factors. Environmental factors include past exposure to effective analgesic agents and verbal suggestions and cues that foster a perception of being given an effective treatment. Environmental factors, in turn, influence the proximate psychologic mediators of placebo analgesia, which include decreased desire for and increased expectations of pain relief. Strategies to maximize placebo analgesic effects in clinical practice could focus on using verbal suggestions and external cues to increase expectations of pain relief and/or decrease the perceived need for pain reduction. Placebo analgesic effects could be minimized in clinical trials by avoiding these same suggestions and cues.

Analgesia↗
PubMed2006

Advanced continuous-contact heat pulse design for efficient temporal summation of second pain (windup).

UNLABELLED: Temporal summation of second pain or windup (WU(SP)) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber-evoked discharges of dorsal horn neurons. Several investigations of heat pain summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of temporal summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU(SP). The present study sought to obtain psychophysical evidence that reliable WU(SP) can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU(SP) was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU(SP) stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU(SP) was characteristic of C fibers. More pronounced second pain and efficient WU(SP) could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU(SP), thereby providing an efficient psychophysical test of this phenomenon. PERSPECTIVE: Temporal summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.

Adult↗
PubMed2006

Quantitative sensory testing for spinal cord stimulation in patients with chronic neuropathic pain.

OBJECTIVE: A prospective pilot study was conducted, attempting to identify objective tests that would help clinicians to assess the efficacy of spinal cord stimulation (SCS) trial preceding permanent device implantation. SETTING: Four university hospitals in the United States and Israel. PARTICIPANTS: Thirteen patients with radicular leg pain due to failed back surgery syndrome (FBSS) or leg pain due to complex regional pain syndrome (CRPS) who were candidates for SCS. METHODS: PARTICIPANTS underwent a series of quantitative sensory tests prior to, and seven days after the initiation of SCS trial. These tests included: vibration threshold (conducted using the VSA 3000; Medoc Inc., Ramat Ishay, Israel), cold threshold, warm threshold, heat pain threshold, phasic heat pain threshold, tonic heat pain threshold (conducted using the TSA 2001; Medoc Inc.), and electrical pain tolerance at 5, 250 and 2000 Hz (administered using the NerveScan 2000; Neurotron, Inc., Baltimore, MD, USA). RESULTS: Useful data were obtained from 12 patients. The results of the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz changed with an SCS trial. These results also correlated with the decision regarding the permanent implantation, which was made independently of them. In contrast, the results of thermal thresholds and tolerance to electrical stimulation at 2000 Hz tests did not change with the SCS trial. CONCLUSIONS: Our findings, which agree with those of a few other studies, suggest that the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz tests can assist the clinician to select the right patients for permanent stimulation.

Adolescent↗
PubMed2005

Individual differences in pain responses.

The experience of pain is characterized by tremendous inter-individual variability. Indeed, an identical noxious stimulus can produce vastly different pain responses across individuals. Historically, scientists have regarded this variability as a nuisance; however, substantial data suggest that these individual differences may provide valuable information that can be used to enhance clinical management of pain. This paper discusses several factors that contribute to individual differences in pain perception, including demographic (ie, sex, age, and ethnicity), genetic, and psychosocial variables. These factors are discussed in the context of the biopsychosocial model of pain, which posits that pain perception is influenced by interactions among biologic, psychosocial, and sociocultural factors. Finally, the clinical and scientific implications of individual differences in pain are discussed.

Age Factors↗
PubMed2005

Morphine responses and experimental pain: sex differences in side effects and cardiovascular responses but not analgesia.

UNLABELLED: Sex differences in analgesic responses to mu opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to mu opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to mu opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed. PERSPECTIVE: This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

Adult↗
PubMed2005

The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans.

Responses to painful stimuli are characterized by tremendous interindividual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism of the mu-opioid receptor gene ( OPRM1 ) was associated with responses to three different experimental pain modalities in a sample of 167 healthy volunteers (96 female, 71 male). Responses to thermal, mechanical, and ischemic pain were assessed in all subjects, and genotyping of OPRM1 was performed, which revealed that the rare A118G allele occurred in 24 females (25%) and 12 males (17%). Statistical analyses indicated that subjects with a rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. Also, a sex by genotype interaction emerged for heat pain ratings at 49 degrees C, such that the rare allele was associated with lower pain ratings among men but higher pain ratings among women. These data indicate an association of a common single nucleotide polymorphism of OPRM1 with mechanical pain responses and that this genotype may be associated with heat pain perception in a sex-dependent manner. This study examines the association of the A118G SNP of OPRM1 to experimental pain sensitivity. The results indicate that the rare allele is associated with higher pressure pain thresholds. These results support previous contentions that OPRM1 may be a pain-relevant gene; however, replication of these findings is needed.

Adult↗
PubMed2005

Sex differences in the associations among psychological factors and pain report: a novel psychophysical study of patients with chronic low back pain.

UNLABELLED: Previous studies have consistently suggested that there are sex differences in pain report, but there is no consensus regarding sex differences in the associations among psychological factors and pain report. This cross-sectional study used a novel, clinically relevant, psychophysical pain-induction technique to examine sex differences between sensory and affective pain report and sex differences in the association of depression, pain related anxiety, and catastrophizing with pain report. Patients with chronic low back pain (N = 53) were recruited from an outpatient spine clinic, and those consenting completed self-report measures of pain-related anxiety, depression, pain catastrophizing, and pain. A measure of induced low back pain was obtained by having study participants perform a protocol on the MedXtrade mark Low-Back Exercise Apparatus. Our results indicated that no sex differences were detected in psychological factors and self-reported or induced low back pain. However, the relationships between pain related anxiety and self-report of low back pain (z = 2.51, P < .05) and between pain-related anxiety and induced low back pain (z = 3.00, P < .05) were significantly stronger in men than women. These findings suggest that anxiety was linked to self-reported and induced low back pain for men, but not for women. PERSPECTIVE: Results of this study suggest that pain-related anxiety has a stronger association with psychophysical and clinical reports of low back pain for men.

Adolescent↗
PubMed2005

Ethnic differences in responses to multiple experimental pain stimuli.

A growing body of literature suggests that the experience of clinical pain differs across ethnocultural groups. Additionally, some evidence indicates greater sensitivity to experimentally induced pain among African Americans; however, most studies have included only one pain modality. This study examined ethnic differences in responses to multiple experimental pain stimuli, including heat pain, cold pressor pain, and ischemic pain. Heat pain threshold and tolerance, ratings of repetitive suprathreshold heat, and ischemic and cold pressor pain threshold and tolerance were assessed in 120 (62 African American, 58 white) healthy young adults. Also, several psychological instruments were administered. No ethnic group differences emerged for threshold measures, but African Americans had lower tolerances for heat pain, cold pressor pain and ischemic pain compared to whites. Ratings of intensity and unpleasantness for suprathreshold heat stimuli were significantly higher among African Americans. African Americans reported greater use of passive pain coping strategies and higher levels of hypervigilance. Controlling for passive pain coping did not account for group differences in pain responses, while controlling for hypervigilance rendered group differences in heat pain tolerance and ischemic pain tolerance non-significant. These findings demonstrate differences in laboratory pain responses between African Americans and whites across multiple stimulus modalities, and effect sizes for these differences in pain tolerance were moderate to large for suprathreshold measures. Hypervigilance partly accounted for group differences. Additional research to determine the mechanisms underlying these effects is warranted.

Adolescent↗