C. Campbell

Pain catastrophizing: a critical review

Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with a number of important pain-related outcomes. In the present review, we first focus our efforts on the conceptualization of pain catastrophizing, highlighting its conceptual history and potential problem areas. We then focus our discussion on a number of theoretical mechanisms of action: appraisal theory, attention bias/information processing, communal coping, CNS pain processing mechanisms, psychophysiological pathways and neural pathways. We then offer evidence to suggest that pain catastrophizing represents an important process factor in pain treatment. We conclude by offering what we believe represents an integrated heuristic model for use by researchers over the next 5 years; a model we believe will advance the field most expediently.

ETHNIC DIFFERENCES IN RESPONSES TO MULTIPLE EXPERIMENTAL PAIN STIMULI

&NA; 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.

Ethnic identity predicts experimental pain sensitivity in African Americans and Hispanics.

Abstract The aim of this study was to examine experimental pain sensitivity in three ethnic groups, African Americans, Hispanic Americans and non‐Hispanic White Americans, and to determine whether ethnic identity is differentially associated with pain sensitivity across ethnic groups. Participants included sixty‐three African American, sixty‐one Hispanic and eighty‐two non‐Hispanic white participants who were assessed using three experimental pain measures: thermal, cold‐pressor and ischemic. Participants’ ethnic identity was assessed using the Multi‐group Ethnic Identity Measure (MEIM). Ethnic group differences in pain responses were observed, with African American and Hispanic subjects showing lower cold and heat pain tolerances than non‐Hispanic White Americans. In addition, pain range (i.e. tolerance‐threshold) was computed for heat, cold and ischemic pain, and the two minority groups again had lower values compared to non‐Hispanic White Americans. Ethnic identity was associated with pain range only for African American and Hispanic groups. Statistically controlling for ethnic identity rendered some of the group differences in pain range non‐significant. These findings indicate that ethnic identity is associated with pain sensitivity in ethnic minority groups, and may partially mediate group differences in pain perception. The results of the present investigation provide evidence of ethnic group differences in responses to experimental pain across multiple noxious stimuli, with both minority groups exhibiting greater sensitivity to laboratory evoked pain compared to non‐Hispanic White Americans.

Discordance between pain and radiographic severity in knee osteoarthritis: Findings from quantitative sensory testing of central sensitization

OBJECTIVE Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures. METHODS A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure-pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1-2 versus 3-4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30). RESULTS Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain-sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race. CONCLUSION The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate-to-severe radiographic evidence of pathologic changes of knee OA.

Sex‐Based Differences in Pain Perception and Treatment

OBJECTIVE This review highlights research on sex-based differences in pain perception and treatment. We sought to illuminate the complex factors contributing to differences in pain and analgesic responses between males and females, ranging from psychosocial to biological processes. DESIGN We reviewed published studies of pain induction by chemical, electric, heat, surgical, or psychological means, and opioid and nonopioid analgesia comparing responses in men and women. RESULTS A substantial body of research indicates that women experience greater clinical pain, suffer greater pain-related distress, and show heightened sensitivity to experimentally induced pain compared with men. Research on sex-based differences in the pain experience and treatment is beginning to uncover patterns that may enable tailoring of pain treatment to individual characteristics. The factors underpinning sex differences in the experience of pain are multifactorial and complex; for example, psychosocial factors such as pain-related catastrophizing may explain sex-based differences in reporting certain types of pain, as women tend to use catastrophizing to a greater degree. Gonadal hormone levels in cycling women also have a substantial impact on pain perception and analgesic response. Women perceive more pain during the luteal phase, and estrogen antagonists provide long-term pain relief in certain situations. CONCLUSIONS Collectively, greater understanding of the factors that commonly and differentially affect the disparity in pain perception, as well as analgesic response, are beginning to illuminate research targets and promising areas of therapeutic intervention for improved pain management.

Cluster analysis of multiple experimental pain modalities.

&NA; 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.

Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy

Summary Topical clonidine significantly reduces pain associated with diabetic neuropathy in subjects with functional nociceptors in the affected skin, as revealed by testing with topical capsaicin. Abstract A length‐dependent neuropathy with pain in the feet is a common complication of diabetes (painful diabetic neuropathy). It was hypothesized that pain may arise from sensitized‐hyperactive cutaneous nociceptors, and that this abnormal signaling may be reduced by topical administration of the α2‐adrenergic agonist, clonidine, to the painful area. This was a randomized, double‐blind, placebo‐controlled, parallel‐group, multicenter trial. Nociceptor function was measured by determining the painfulness of 0.1% topical capsaicin applied to the pretibial area of each subject for 30 minutes during screening. Subjects were then randomized to receive 0.1% topical clonidine gel (n = 89) or placebo gel (n = 90) applied 3 times a day to their feet for 12 weeks. The difference in foot pain at week 12 in relation to baseline, rated on a 0–10 numerical pain rating scale (NPRS), was compared between groups. Baseline NPRS was imputed for missing data for subjects who terminated the study early. The subjects treated with clonidine showed a trend toward decreased foot pain compared to the placebo‐treated group (the primary endpoint; P = 0.07). In subjects who felt any level of pain to capsaicin, clonidine was superior to placebo (P < 0.05). In subjects with a capsaicin pain rating ⩾2 (0–10, NPRS), the mean decrease in foot pain was 2.6 for active compared to 1.4 for placebo (P = 0.01). Topical clonidine gel significantly reduces the level of foot pain in painful diabetic neuropathy subjects with functional (and possibly sensitized) nociceptors in the affected skin as revealed by testing with topical capsaicin. Screening for cutaneous nociceptor function may help distinguish candidates for topical therapy for neuropathic pain.

Polymorphisms in the GTP cyclohydrolase gene (GCH1) are associated with ratings of capsaicin pain.

Abstract Though it is clear that genomic variability plays an integral role in accounting for pain sensitivity, controversy exists over which genes are involved. While recent data suggest a “protective” (i.e., less pain) haplotype in the GTP cyclohydrolase (GCH1) gene, other research has failed to confirm this association. Possibly, the effects of single nucleotide polymorphisms (SNPs) vary depending on the pain task. The current investigation analyzed the association of five previously identified GCH1 SNPs with ratings of pain induced by topical high concentration (10%) capsaicin applied to the skin of 39 healthy human volunteers. Each of the GCH1 polymorphisms was associated with lower pain ratings. When combined, three of the five accounted for a surprisingly high 35% of the inter‐individual variance in pain ratings. We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin.

Ethnic differences in diffuse noxious inhibitory controls.

UNLABELLED Substantial evidence indicates that the experience of both clinical and experimental pain differs among ethnic groups. Specifically, African Americans generally report higher levels of clinical pain and greater sensitivity to experimentally induced pain; however, little research has examined the origins of these differences. Differences in central pain-inhibitory mechanisms may contribute to this disparity. Diffuse noxious inhibitory controls (DNIC), or counterirritation, is a phenomenon thought to reflect descending inhibition of pain signals. The current study assessed DNIC in 57 healthy young adults from 2 different ethnic groups: African Americans and non-Hispanic whites. Repeated assessments of the nociceptive flexion reflex (NFR) as well as ratings of electrical pain were obtained before, during, and after an ischemic arm pain procedure (as well as a sham procedure). The DNIC condition (ie, ischemic arm pain) produced substantial reductions in pain ratings as well as electrophysiologic measures of the NFR for all participants when compared with the sham condition (P < .001). The DNIC condition produced significantly greater reductions in verbal pain ratings among non-Hispanic whites when compared with African Americans (P = .02), whereas ethnic groups showed comparable reductions in NFR. The findings of this study suggest differences in endogenous pain inhibition between African Americans and non-Hispanic whites and that additional research to determine the mechanisms underlying these effects is warranted. PERSPECTIVE This study adds to the growing literature examining ethnic differences in experimental pain perception. Our data suggest that these variations may be influenced by differences in descending inhibition.

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.