Jennifer L. DelVentura

Pain catastrophizing is related to temporal summation of pain but not temporal summation of the nociceptive flexion reflex

&NA; Pain catastrophizing is associated with enhanced temporal summation of pain (TS‐Pain). However, because prior studies have found that pain catastrophizing is not associated with a measure of spinal nociception (nociceptive flexion reflex [NFR] threshold), this association may not result from changes in spinal nociceptive processes. The goal of the present study in healthy participants was to examine the relationship between trait (traditional) and state (situation‐specific) pain catastrophizing and temporal summation of NFR (TS‐NFR) and TS‐Pain. A secondary goal was to replicate prior findings concerning relationships between catastrophizing and NFR threshold, electrocutaneous pain threshold, and sensory and affective ratings of electrocutaneous stimuli. All analyses controlled for depression symptoms, pain‐related anxiety, and participant sex. As expected, multiple regression analyses indicated that neither trait nor situation‐specific catastrophizing was associated with NFR threshold, but that situation‐specific catastrophizing was associated with pain ratings. Multilevel linear growth models of TS data indicated that situation‐specific catastrophizing was associated with TS‐Pain but not TS‐NFR. Trait catastrophizing was not related to TS‐Pain or TS‐NFR. Together, these results confirm prior studies that indicate that catastrophizing enhances pain via supraspinal processes rather than spinal processes. Moreover, because catastrophizing was associated with TS‐Pain but not TS‐NFR, caution is warranted when using pain ratings to infer temporal summation of spinal nociceptive processes. Pain catastrophizing, a set of cognitive–affective processes associated with enhanced pain, is not associated with a physiological correlate of wind‐up in human beings (temporal summation of the nociceptive flexion reflex).

Emotional modulation of pain and spinal nociception in fibromyalgia

&NA; Fibromyalgia is associated with disrupted emotional processing and emotional modulation of pain, but intact descending emotional modulation of spinal nociception. &NA; Fibromyalgia (FM) is characterized by widespread pain, as well as affective disturbance (eg, depression). Given that emotional processes are known to modulate pain, a disruption of emotion and emotional modulation of pain and nociception may contribute to FM. The present study used a well‐validated affective picture‐viewing paradigm to study emotional processing and emotional modulation of pain and spinal nociception. Participants were 18 individuals with FM, 18 individuals with rheumatoid arthritis (RA), and 19 healthy pain‐free controls (HC). Mutilation, neutral, and erotic pictures were presented in 4 blocks; 2 blocks assessed only physiological‐emotional reactions (ie, pleasure/arousal ratings, corrugator electromyography, startle modulation, skin conductance) in the absence of pain, and 2 blocks assessed emotional reactivity and emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations over the sural nerve. In general, mutilation pictures elicited displeasure, corrugator activity, subjective arousal, and sympathetic activation, whereas erotic pictures elicited pleasure, subjective arousal, and sympathetic activation. However, FM was associated with deficits in appetitive activation (eg, reduced pleasure/arousal to erotica). Moreover, emotional modulation of pain was observed in HC and RA, but not FM, even though all 3 groups evidenced modulation of NFR. Additionally, NFR thresholds were not lower in the FM group, indicating a lack of spinal sensitization. Together, these results suggest that FM is associated with a disruption of supraspinal processes associated with positive affect and emotional modulation of pain, but not brain‐to‐spinal cord circuitry that modulates spinal nociceptive processes.

Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD)

Summary MDD is associated with disrupted emotional processing and emotional modulation of pain, but intact descending emotional modulation of spinal nociception. Abstract Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. Two blocks assessed physiological‐emotional reactions (pleasure/arousal ratings, corrugator electromyography (EMG), startle modulation, skin conductance) in the absence of pain and 2 blocks assessed emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations. Results indicated pictures generally evoked the intended emotional responses; erotic pictures elicited pleasure, subjective arousal, and smaller startle magnitudes, whereas mutilation pictures elicited displeasure, corrugator EMG activation, and subjective/physiological arousal. However, emotional processing was partially disrupted in MDD, as evidenced by a blunted pleasure response to erotica and a failure to modulate startle according to a valence linear trend. Furthermore, emotional modulation of pain was observed in controls but not MDD, even though there were no group differences in NFR threshold or emotional modulation of NFR. Together, these results suggest supraspinal processes associated with emotion processing and emotional modulation of pain may be disrupted in MDD, but brain to spinal cord processes that modulate spinal nociception are intact. Thus, emotional modulation of pain deficits may be a phenotypic marker for future pain risk in MDD.

Standardizing procedures to study sensitization of human spinal nociceptive processes: Comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR)

Temporal summation of pain (TS-pain) is the progressive increase in pain ratings during a series of noxious stimulations. TS-pain has been used to make inferences about sensitization of spinal nociceptive processes; however, pain report can be biased thereby leading to problems with this inference. Temporal summation of the nociceptive flexion reflex (TS-NFR, a physiological measure of spinal nociception) can potentially overcome report bias, but there have been few attempts (generally with small Ns) to standardize TS-NFR procedures. In this study, 50 healthy participants received 25 series of noxious electric stimulations to evoke TS-NFR and TS-pain. Goals were to: 1) determine the stimulation frequency that best elicits TS-NFR and reduces electromyogram (EMG) contamination from muscle tension, 2) determine the minimum number of stimulations per series before NFR summation asymptotes, 3) compare NFR definition intervals (90-150ms vs. 70-150ms post-stimulation), and 4) compare TS-pain and TS-NFR when different stimulation frequencies are used. Results indicated TS-NFR should be elicited by a series of three stimuli delivered at 2.0Hz and TS-NFR should be defined from a 70-150ms post-stimulation scoring interval. Unfortunately, EMG contamination from muscle tension was greatest during 2.0Hz series. Discrepancies were noted between TS-NFR and TS-pain which raise concerns about using pain ratings to infer changes in spinal nociceptive processes. And finally, some individuals did not have reliable NFRs when the stimulation intensity was set at NFR threshold during TS-NFR testing; therefore, a higher intensity is needed. Implications of findings are discussed.

Natural variation in testosterone is associated with hypoalgesia in healthy women.

Objective:Sex differences in pain are well established, with women reporting greater incidence of clinical pain and heightened responsivity to experimental pain stimuli relative to men. Sex hormones (ie, estrogens, progestins, androgens) could contribute to extant differences in pain sensitivity between men and women. Despite this, there has been limited experimental research assessing the relationship between pain and sex hormones. The purpose of this study was to extend previous research and examine the association between sex hormones and nociceptive processing in healthy women. Materials and Methods:A total of 40 healthy women were tested during the mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle (testing order counterbalanced). Salivary estradiol, progesterone, and testosterone were collected at each testing session and pain was examined from electrocutaneous threshold/tolerance, ischemia threshold/tolerance, and McGill Pain Questionnaire-Short Form ratings of noxious stimuli. Nociceptive flexion reflex threshold was assessed as a measure of spinal nociception. Results:Overall, there were no significant menstrual phase-related differences in pain outcomes. Nonetheless, variability in testosterone (and to a lesser degree estradiol) was associated with pain; testosterone was antinociceptive, whereas estradiol was pronociceptive. No hormone was associated with nociceptive flexion reflex threshold. Discussion:Although future research is needed to replicate and extend these findings to clinical populations (ie, chronic pain, premenstrual dysphoric disorder), results from the present study indicate that menstrual phase-related changes in sex hormones have minimal influence on experimental pain. However, individual differences in testosterone may play a protective role against pain in healthy women.

Do sex hormones influence emotional modulation of pain and nociception in healthy women

Sex hormones may contribute to inter- and intra-individual differences in pain by influencing emotional modulation of pain and nociception. To study this, a well-validated picture-viewing paradigm was used to assess emotional modulation of pain and the nociceptive flexion reflex (NFR; physiologic measure of nociception) during mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle in healthy normally cycling women (n=40). Salivary estradiol, progesterone, and testosterone were assessed at each testing session. Emotional modulation of pain/NFR did not differ across menstrual phases, but low estradiol was associated with weaker emotional modulation of NFR (during all phases) and emotional modulation of pain (ovulatory and late-luteal phases). Given evidence that a failure to emotionally modulate pain might be a risk factor for chronic pain, low estradiol may promote chronic pain via this mechanism. However, future research is needed to extend these findings to women with disturbances of pain, emotion, and/or sex hormones.

Exploring pain processing differences in Native Americans.

OBJECTIVE Several chronic pain conditions are more prevalent in Native Americans than in any other group in the United States; however, little has been done to identify factors contributing to this disparity. The study presented here was designed to examine whether there were pain processing differences in Native Americans relative to non-Hispanic White controls. METHODS Participants were healthy, pain-free Native Americans (n = 22, 8 females) and non-Hispanic Whites (n = 20, 7 females). Pain processing was assessed from electric pain threshold/tolerance, ischemia pain threshold/tolerance, nociceptive flexion reflex threshold (NFR; an electrophysiological measure of spinal nociception), pain ratings of suprathreshold electric stimuli, and temporal summation of pain and NFR (an electrophysiological measure of spinal cord sensitization). The institutional review board approved all procedures. RESULTS Compared to non-Hispanic Whites, Native Americans had dampened pain perception (higher ischemia pain tolerance, higher electric pain threshold, lower ratings of electric stimuli). Additionally, temporal summation of NFR was reduced in Native Americans, suggesting sensitization was reduced at the spinal level. CONCLUSIONS Findings suggest Native Americans have dampened pain and pain signaling, perhaps due to overactivation of descending pain inhibition mechanisms. Given research indicating that other ethnic groups at risk for chronic pain (e.g., African Americans) show enhanced pain and enhanced central sensitization on experimental pain measures, chronic pain risk could be different for Native Americans, thus emphasizing the need for different treatment interventions.

Respiration-Induced Hypoalgesia: Exploration of Potential Mechanisms

UNLABELLED Slow breathing is used as a means to reduce pain, yet the mechanisms responsible for respiration-induced hypoalgesia are poorly understood. The present study asked 30 healthy participants (M(age) = 21 years, M(education) = 15 years, 80% white non-Hispanic) to breathe at normal, slow (50% normal), and fast (125% normal) rates while constant-intensity, suprathreshold electric stimulations were delivered to the sural nerve to elicit pain and the nociceptive flexion reflex (NFR, a measure of spinal nociception). Stimulations were equally balanced across inhalations and exhalations to determine whether parasympathetic activation during exhalations contributes to hypoalgesia. Respiration rate, heart rate variability (HRV, a measure of parasympathetic activity), heart rate, and subjective arousal were assessed as manipulation checks. Slow breathing reduced pain relative to normal breathing and fast breathing, but NFR was not influenced by breathing. Further, pain and NFR did not differ between exhalations and inhalations, and changes in HRV did not correlate with changes in pain or NFR. Together, these findings suggest that respiration-induced hypoalgesia does not require gating of spinal nociception or changes in parasympathetic activity. PERSPECTIVE Slow breathing reduced pain relative to normal and fast breathing. This respiration-induced hypoalgesia does not appear to be due to gating of spinal nociception or changes in parasympathetic activity.

Anxiety sensitivity does not enhance pain signaling at the spinal level.

Objectives:Anxiety sensitivity (AS) is the fear of anxiety-related sensations and its perceived harmful consequences. AS is associated with enhanced pain and worsened pain outcomes, suggesting it is a contributing factor in acute and chronic pain. However, the mechanisms that mediate the relationship between AS and pain are currently unknown. This study assessed the relationship between AS and 2 measures of spinal nociceptive processes (ie, nociceptive flexion reflex and temporal summation of nociceptive flexion reflex) and measures of subjective pain. This allowed us to determine whether AS engages descending cerebrospinal processes to facilitate pain signaling at spinal levels. Methods:AS was assessed in healthy men and women using the Anxiety Sensitivity Index-Revised. Then pain processing was assessed from electric pain threshold, nociceptive flexion reflex threshold, temporal summation of pain, temporal summation of nociceptive flexion reflex, and McGill Pain Questionnaire sensory and affective pain ratings. Associations among variables were assessed using Winsorized correlations (a robust and statistically powerful analytic method). Results:AS was positively associated with sensory pain ratings, affective pain ratings, and temporal summation of pain, but was unrelated to all other outcomes. Discussion:Given that AS was not significantly associated with measures of spinal nociception, these results suggest that AS may exert its influence on pain processing at the supraspinal, rather than the spinal level.

Emotional modulation of pain and spinal nociception in persons with severe insomnia symptoms.

BackgroundImpaired sleep enhances pain, perhaps by disrupting pain modulation.PurposeGiven that emotion modulates pain, the present study examined whether emotional modulation of pain and nociception is impaired in persons with severe insomnia symptoms relative to controls.MethodsInsomnia group (n = 12) met the International Classification of Diseases, tenth revision symptoms for primary insomnia and controls (n = 13) reported no sleep impairment. Participants were shown emotionally evocative pictures (mutilation, neutral, and erotica) during which suprathreshold pain stimuli were delivered to evoke pain and the nociceptive flexion reflex (NFR; physiological correlate of spinal nociception).ResultsEmotional responses to pictures were similar in both groups, except that subjective valence/pleasure ratings were blunted in insomnia. Emotional modulation of pain and NFR was observed in controls, but only emotional modulation of NFR was observed in insomnia.ConclusionsConsistent with previous findings, pain modulation is disrupted in insomnia, which might promote pain. This may stem from disrupted supraspinal circuits not disrupted brain-to-spinal cord circuits.