Daniel J. Clauw

Pain Sensitivity as a Correlate of Clinical Status in Individuals With Chronic Low Back Pain

STUDY DESIGN A cross-sectional study of baseline correlates of clinical pain and functional status in consecutive patients being treated for chronic low back pain. OBJECTIVES To determine if an individuals global pain sensitivity, measured by experimental pain threshold to pressure at various regions of the body, is associated with baseline measures of clinical pain and physical functioning. SUMMARY OF BACKGROUND DATA Previous studies have demonstrated that in individuals with chronic low back pain, clinical pain and functional status are significantly associated with demographic, structural, and psychosocial factors. However, a large portion of variance remains unexplained. Because pain sensitivity (tenderness) has been shown to occur as a continuum in the population, the authors sought to determine if such sensitivity might be associated with clinical status in chronic low back pain, beyond what is known regarding demographic, structural, and psychosocial factors. METHODS Forty-five patients with chronic low back pain were assessed for a variety of demographic, structural, and psychosocial factors, which previously have been shown to contribute to clinical status. In addition, all patients underwent testing for pain tolerance and threshold at various areas of the body. RESULTS Age, degree of structural abnormality observed on magnetic resonance imaging, and depressive symptoms were all significantly correlated with either clinical pain or functional status. Pain sensitivity, the target of this investigation, accounted for significant proportions of variance in functional status and pain, even after controlling for demographic, structural, and psychosocial variables. CONCLUSIONS These pilot data suggest that an individuals experimental pain threshold (a measure of tenderness) is associated with baseline functional status and pain in cases of chronic low back pain and may represent an important domain warranting further investigation.

Rhinitis symptoms in chronic fatigue syndrome.

BACKGROUND Atopy and allergic rhinitis are thought to be increased in prevalence in chronic fatigue syndrome (CFS). METHODS To investigate this hypothesis, 51 CFS (CFS), 34 normal (N), 27 allergic rhinitis (AR), and 17 patients with other rheumatologic diseases filled out an Airway Symptom Severity self-report questionnaire to determine the frequencies of nasal, sinus, and chest symptoms, and a Systemic Complaints self-report questionnaire to determine the frequencies of complaints referable to neurologic, rheumatologic, gastrointestinal, and other systems. All subjects received a standard set of allergy skin tests, and were subdivided into those with positive and negative results. RESULTS Allergy skin tests were positive in 35% of CFS and 44% of N subjects (difference not significant by Chi2). Significant rhinitis complaints were present in 83% of skin test positive CFS, 76% of skin test negative CFS, 74% of AR, and 23% of N subjects. Systemic Complaints scores were significantly elevated in skin test positive (94%) and negative (94%) CFS groups compared with AR (35%) and N (6%) groups. This score could significantly discriminate between CFS and N subjects. CONCLUSIONS These data indicate that in this CFS population, 24% had no significant rhinitis complaints, 30% had positive skin tests suggesting the potential for allergic rhinitis complaints, and 46% had nonallergic rhinitis. The mechanism of the nonallergic component may offer insights into the pathogenesis of CFS.

The overlap between fibromyalgia and inflammatory rheumatic disease: When and why does it occur?

Fibromyalgia is a common condition that affects 2-4% of the population and is characterized by widespread pain, fatigue, and a number of other symptoms. There is evidence to suggest that fibromyalgia occurs much more frequently than expected in individuals with inflammatory rheumatic disorders. At present, it is not clear whether the inflammatory disorder leads to fibromyalgia or vice versa, but plausible mechanisms exist for either scenario. The coexistence of fibromyalgia and inflammatory disorders can lead to considerable difficulty in both diagnosis and treatment. In this article, the reasons that these two types of disorders can coexist are reviewed, and an approach to the diagnosis and management of individuals with components of both fibromyalgia and an inflammatory disorder is suggested.

Nasal secretion analysis in allergic rhinitis, cystic fibrosis, and nonallergic fibromyalgia/chronic fatigue syndrome subjects.

Rhinitis symptoms are present in approximately 70% of subjects with fibromyalgia and chronic fatigue syndrome (FM/CFS). Because only 35% to 50% have positive allergy skin tests, nonallergic mechanisms may also play a role. To better understand the mechanisms of nonallergic rhinitis in FM/CFS, nasal lavages were performed, and markers of vascular permeability, glandular secretion, and neutrophil and eosinophil infiltration measured in 27 nonallergic FM/CFS, 7 allergic rhinitis, 7 cystic fibrosis, and 9 normal subjects. Allergic rhinitis subjects had significantly increased vascular permeability (IgG) and ECP levels. Cystic fibrosis subjects had significantly higher elastase and total protein levels. There were no significant differences between FM/CFS and normal lavage fluids. Analysis of the constituents of nasal mucus provides information about ongoing secretory processes in rhinitis. There were no differences in the basal secretion of these markers of vascular permeability, submucosal gland serous cell secretion, eosinophil and neutrophil degranulation in nonallergic FM/CFS subjects. This suggests that constitutively active secretory processes that regulate continuous production of nasal secretions are not altered in FM/CFS. Future studies should examine alternative mechanisms such as inducible, irritant-activated, or reflex-mediated effects.

A tender sinus does not always mean rhinosinusitis

BACKGROUND: Sinus tenderness has not been quantitatively assessed. OBJECTIVE: We sought to compare sinus and systemic tenderness in rhinosinusitis, allergic rhinitis, and chronic fatigue syndrome (CFS), and healthy (non-CFS) groups. METHODS: Cutaneous pressures (kg/cm2) causing pain at 5 sinus and 18 systemic sites were measured in acute and chronic rhinosinusitis, active allergic rhinitis, healthy non-CFS/no rhinosinusitis, and CFS subjects. RESULTS: Sinus thresholds differed significantly (P ≤ 10−11, ANOVA) between non-CFS/no rhinosinusitis (1.59 ± 0.14 kg/cm2, mean ± 95% CI, n = 117), allergic rhinitis (1.19 ± 0.31, n = 30), exacerbations of chronic rhinosinusitis (1.25 ± 0.26, n = 25), non-CFS/chronic rhinosinusitis (1.23 ± 0.27, n = 23), acute rhinosinusitis (1.10 ± 0.20, n = 22), CFS/no rhinosinusitis (0.98 ± 0.15, n = 70), and CFS/chronic rhinosinusitis (0.78 ± 0.12, n = 56). Systemic pressure thresholds were lower for CFS (1.46 ± 0.15) than for non-CFS (2.67 ± 0.22, P ≤ 10−11). CONCLUSIONS: The lower sinus thresholds of rhinosinusitis groups validated the sign of sinus tenderness. Sinus and systemic thresholds were both 44% lower in CFS than in non-CFS subjects, suggesting that systemic hyperalgesia contributed to CFS sinus tenderness and “rhinosinusitis” complaints. Tenderness to palpation or percussion is one of the clinical hallmarks of acute and chronic rhinosinusitis. 1,2 This sign may equate with the subjective sensation of pain experienced by rhinosinusitis subjects and so may be indicative of either excessive nociceptive nerve depolarization or centrally mediated hyperalgesia. Several peripheral mechanisms may contribute, including the release of excessive amounts of mediators that activate sensory neurons (eg, bradykinin); increased sensitivity of type C fibers to mediators generated during acute or chronic inflammation (eg, endothelin, bradykinin); or hyperresponsiveness due to facilitation of neural depolarization induced by prostaglandins, leukotriene B4, and neurotropic cytokines (eg, nerve growth factor). 3 Central factors may also cause hyperalgesia by modulating the spinal cord actions of large-diameter, low-threshold A

IgE levels are the same in chronic fatigue syndrome (CFS) and control subjects when stratified by allergy skin test results and rhinitis types

bT-fiber touch or other sensory nerves that innervate the trigeminal dermatome and mucosal areas (“ mucotome”). Sites of alteration may include the spinal dorsal horn somatosensory region and higher central nervous system sites of nociceptive regulation 4 and dysfunction of descending antinociceptive aminergic neural circuits. 3 Although the sign of tenderness is commonly used to diagnose rhinosinusitis, the degree of hyperalgesia has not been quantified in comparison to the sensitivity of control subjects. Therefore, we used dolorimetry (algometry) to measure sinus tenderness. 4 A strain gauge was pressed against the sinus regions until pain was elicited. The mean pressure required to cause pain was considered to be the sinus pressure threshold (kg/cm2). Systemic pressure threshold was determined for 18 “tender points” that are used to diagnose fibromyalgia. 4 Sinus and systemic tenderness were compared in acute rhinosinusitis, chronic rhinosinusitis, chronic rhinosinusitis with acute exacerbations, active allergic rhinitis, and control groups. Chronic fatigue syndrome (CFS) subjects formed one control group. They have a high prevalence of rhinitis complaints (60% to 80%) but there is no evidence of mucosal inflammation based on measures of mucus constituents including neutrophil elastase and eosinophil cationic protein, 5 cytokines, 6 or any bias toward atopic disease as assessed by serum IgE levels. 4 Another reference population consisted of healthy subjects not fulfilling the criteria for CFS (non-CFS subjects). The impact of chronic rhinosinusitis complaints was assessed in CFS/chronic rhinosinusitis, non-CFS/chronic rhinosinusitis, and their corresponding no-rhinosinusitis subpopulations.

Fibromyalgia Associated Syndromes

BACKGROUND Chronic fatigue syndrome (CFS) has an uncertain pathogenesis. Allergies have been suggested as one cause. OBJECTIVE The aim of this study was to compare serum immunoglobulin (Ig)E in CFS and control subjects to determine whether IgE levels were elevated in CFS. This would be suggestive of increased atopy in CFS. METHODS IgE was measured by quantitative ELISA (sandwich) immunoassay in 95 CFS and 109 non-CFS control subjects. Subjects were classified by positive or negative allergy skin tests (AST) and rhinitis questionnaires (rhinitis score, RhSc) into four rhinitis types: nonallergic rhinitis (NAR with positive RhSc and negative AST); allergic rhinitis (AR with positive AST and RhSc); atopic/no rhinitis (AST positive/RhSc negative); and nonatopic/no rhinitis (both AST and RhSc negative) subjects. RESULTS IgE was not significantly different between control (128 +/- 18 IU/mL, mean +/- SEM) and CFS (133 +/- 43 IU/mL) groups, or between control and CFS groups classified into the four rhinitis types. IgE was significantly higher in subjects with positive AST whether or not they had positive RhSc or CFS symptoms. CONCLUSIONS Elevated IgE and positive AST indicate allergen sensitization, but are not necessarily indicators of symptomatic allergic diseases. There was no association between IgE levels and CFS, indicating that atopy was probably not more prevalent in CFS. Therefore, TH2-lymphocyte and IgE-mast cell mechanisms are unlikely causes of CFS.

Pilot Study of an Internet-Based Self-Management Program for Symptom Control in Patients With Early-Stage Breast Cancer

SUMMARY Objectives: To describe the syndromes that share overlapping clinical features with fibromyalgia [FMS]. Findings: There are a number of semantic terms currently used to described systemic syndromes that share overlapping features with FMS. These include chronic fatigue syndrome, multiple chemical sensitivity, somatoform disorders, and Gulf War Illnesses. There are also a number of regional or “organ-specific” syndromes that overlap with these conditions that have as their common features regional pain, with and without dysfunction of internal organs. Conclusions: In aggregate, chronic multisymptom illnesses such as FMS are extremely common. Hallmarks of these syndromes include non-nociceptive pain, fatigue, memory difficulties, and dysfunction of visceral organs.

Improving physical functional status in patients with fibromyalgia: a brief cognitive behavioral intervention.

PURPOSE Many survivors of breast cancer experience an array of chronic symptoms, including pain, insomnia, and fatigue. Few effective therapies have been identified. Behavioral management programs to address similar symptom clusters in other chronic conditions have been effective. The objective of this study was to determine the effect of an Internet-based lifestyle and behavioral self-management program on cancer-related symptoms. PATIENTS AND METHODS Women with stage 0 to 3 breast cancer who reported insomnia, pain, or fatigue as their primary symptom of concern during the 7 days before enrollment were enrolled. Local therapies and/or chemotherapy were completed at least 3 months before enrollment. Patients were assessed at baseline and after 8 weeks, and they completed the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Profile and Patient Global Impression of Change (PGIC) questionnaire electronically. Change in each of the eight symptom domains was assessed. RESULTS Fifty patients enrolled. In the 45 patients with both baseline and 8-week PROMIS data, statistically significant improvements in anxiety, sleep, fatigue, activity level, and pain severity were reported. Of the 35 patients who responded to the PGIC, 62.9% reported improvement in their primary symptom. Those who reported fatigue as their primary symptom reported greatest overall benefit in multiple symptom improvement, including improvements in fatigue, anxiety, pain severity, pain interference, and participation in social activities. CONCLUSIONS These findings suggest that this lifestyle and behavioral management program may improve multiple symptoms in breast cancer survivors when delivered via the Internet. Randomized studies are warranted to evaluate the efficacy of the online intervention compared with standard symptom management approaches and to identify patients most likely to benefit.