Do We Measure What Patients Feel?: An Analysis of Correspondence Between Somatosensory Modalities Upon Quantitative Sensory Testing and Self-reported Pain Experience.

OBJECTIVES: Hyperalgesia and allodynia are typical signs of neuropathic pain. Quantitative sensory testing (QST) is a validated tool to clinically assess these phenomena. However, whether QST reveals findings that are reported by the patients is unclear. The aim of this study was therefore to investigate the association between self-reported symptoms assessed with the painDETECT questionnaire (PDQ) with results of validated QST. MATERIALS AND METHODS: PDQ and QST data of 96 patients with chronic neuropathic pain were analyzed. Questions upon presence of painful light touch, painful cold or heat, light pressure triggering pain, and numbness upon PDQ were compared with findings of dynamic mechanical allodynia, increased sensitivity to heat, cold, or pressure pain as well as loss of detection upon QST, respectively. RESULTS: Self-reported pain symptoms upon PDQ showed only a small to moderate concordance with corresponding signs assessed upon QST, whereat the highest, but still only moderate association between self-reported symptoms and measured signs could be obtained for self-reported presence of painful light touch and dynamic mechanical allodynia upon QST. However, the positive and negative likelihood ratio to predict QST values with PDQ scores did not reach convincing values. DISCUSSION: Results demonstrate that self-reported PDQ symptoms cannot predict abnormal QST values. The poor predictive power of the PDQ may depend on several factors based on possibility of comparison between PDQ and QST and also on methodical issues. Both, symptoms (questionnaires) and signs address complementary aspects of the pain experience and should be considered for diagnosis and treatment of neuropathic pain.

Short Report: TRPV1-polymorphism 1911 A>G alters capsaicin-induced sensory changes in healthy subjects.

BACKGROUND: C-fibers express transient receptor potential (TRP) channels. These high-voltage gated channels function as integrators of different physical stresses (e.g. heat, protons, ATP). Additionally channel activation can be induced by capsaicin. Topically applied, capsaicin elicits burning pain, heat and mechanical hyperalgesia and serves as a human surrogate model for pain. It was suggested that the TRPV1-variant rs8065080 (1911A>G) plays a pivotal role in patients with neuropathic pain syndromes. We investigated the effect of this TRPV1-SNP on thermal sensitivity and superficial skin perfusion in 25 healthy subjects. METHODS AND FINDINGS: Nine subjects being homozygous TRPV1 wild type (AA), 8 heterozygous (AG) and 8 homozygous variant (GG) carriers were selected out of a pool of genotyped healthy individuals. Under physiological conditions (no capsaicin application), there was no statistical significant difference in thermal thresholds or skin perfusion between carriers of different TRPV1 1199A>G genotypes. However, intra-individual calculations (Δ% pre vs. post capsaicin) revealed (1) less warm-detection in AA/AG (-82.1%) compared to GG (-13.1%) and (2) a gain of heat pain sensitivity in AA/AG (+22.2%) compared to GG carriers (+15.6%) after adjustment for perfusion measurements ((1)p = 0.009, (2)p = 0.021). CONCLUSION: Presence of homozygous variant TRPV1 genotype (GG) demonstrated less capsaicin-induced warm hypoesthesia in warm-detection and less capsaicin-induced heat pain sensitivity suggesting an altered channel function. This demonstrates not only the functional influence of TRPV1 rs8065080 polymorphism itself; it further more underpins the relevance of genotyping-based approaches in both patients and surrogate models of neuropathic pain in healthy volunteers.

Axial low back pain: one painful area--many perceptions and mechanisms.

Axial low back pain can be considered as a syndrome with both nociceptive and neuropathic pain components (mixed-pain). Especially neuropathic pain comprises a therapeutic challenge in practical experience and may explain why pharmacotherapy in back pain is often disappointing for both the patient and the therapist. This survey uses epidemiological and clinical data on the symptomatology of 1083 patients with axial low back pain from a cross sectional survey (painDETECT). Objectives were (1) to estimate whether neuropathic pain contributes to axial low back pain and if so to what extent. (2) To detect subgroups of patients with typical sensory symptom profiles and to analyse their demographic data and co-morbidities. (3) To compare patients with and without prior intervertebral disc surgery (IVD). Neuropathic pain components could be detected in 12% of the entire cohort. Cluster analyses of these patients revealed five distinct subgroups of patients showing a characteristic sensory profile, i.e. a typical constellation and combination of symptoms. All subgroups occurred in relevant numbers and some showed distinct neuropathic characteristics while others showed nociceptive features. Post-IVD-surgery patients showed a tendency to score more "neuropathic" than patients without surgery (not statistically significant). Axial low back pain has a high prevalence of co-morbidities with implication on therapeutic aspects. From these data it can be concluded that sensory profiles based on descriptor severity may serve as a better predictor for therapy assessment than pain intensity or sole diagnosis alone. Standardized phenotyping of pain symptoms with easy tools may help to develop an individualized therapy leading to a higher success rate in pharmacotherapy of axial low back pain.

Subgrouping of patients with neuropathic pain according to pain-related sensory abnormalities: a first step to a stratified treatment approach.

BACKGROUND: Patients with neuropathic pain present with various pain-related sensory abnormalities. These sensory features form different patterns or mosaics-the sensory profile-in individual patients. One hypothesis for the development of sensory profiles is that distinct pathophysiological mechanisms of pain generation produce specific sensory abnormalities. Several controlled trials of promising new drugs have produced negative results, but these findings could have been a result of heterogeneity in the patient population. Subgrouping patients on the basis of individual sensory profiles could reduce this heterogeneity and improve trial design. RECENT DEVELOPMENTS: A statistical categorisation of patients with neuropathic pain showed that subgroups of patients with distinct sensory profiles who perceive their pain differently do exist across a range of neuropathic disorders, although some distinct disorder-specific profiles were also detected. Results of the first clinical trials to use the subgroup approach at baseline could show a superior effect of the study drugs in specific subgroups, rather than in the entire cohort of patients. WHERE NEXT?: A new classification of neuropathic pain should take into account subgroups of patients with different sensory profiles. Sensory phenotyping has the potential to improve clinical trial design by enriching the study population with potential treatment responders, and might lead to a stratified treatment approach and ultimately to personalised treatment.

A case of pain, motor impairment, and swelling of the arm after acute herpes zoster infection.

Complex regional pain syndrome (CRPS) and postherpetic neuralgia (PHN) represent neuropathic pain syndromes that may appear with similar clinical signs and symptoms. Medical history and clinical distribution of symptoms and signs (PHN typically at the thorax; CRPS typically at the limbs) is obvious in most cases, helping to discriminate between both disorders. Here, we present a patient suffering from CRPS II following PHN of one upper extremity. This case demonstrates that both etiology and part of the body affected by a neuropathy influence the pain phenotype.

G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation.

Molecular danger signals attract neutrophilic granulocytes (polymorphonuclear leukocytes (PMNs)) to sites of infection. The G protein-coupled receptor (GPR) 43 recognizes propionate and butyrate and is abundantly expressed on PMNs. The functional role of GPR43 activation for in vivo orchestration of immune response is unclear. We examined dextrane sodium sulfate (DSS)-induced acute and chronic intestinal inflammatory response in wild-type and Gpr43-deficient mice. The severity of colonic inflammation was assessed by clinical signs, histological scoring, and cytokine production. Chemotaxis of wild-type and Gpr43-deficient PMNs was assessed through transwell cell chemotactic assay. A reduced invasion of PMNs and increased mortality due to septic complications were observed in acute DSS colitis. In chronic DSS colitis, Gpr43(-/-) animals showed diminished PMN intestinal migration, but protection against inflammatory tissue destruction. No significant difference in PMN migration and cytokine secretion was detected in a sterile inflammatory model. Ex vivo experiments show that GPR43-induced migration is dependent on activation of the protein kinase p38alpha, and that this signal acts in cooperation with the chemotactic cytokine keratinocyte chemoattractant. Interestingly, shedding of L-selectin in response to propionate and butyrate was compromised in Gpr43(-/-) mice. These results indicate a critical role for GPR43-mediated recruitment of PMNs in containing intestinal bacterial translocation, yet also emphasize the bipotential role of PMNs in mediating tissue destruction in chronic intestinal inflammation.

Role of NOD2/CARD15 in coronary heart disease.

BACKGROUND: Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion. Genetic variation in the CARD15 gene, which encodes NOD2, was previously shown to result in a barrier defect that causes chronic inflammatory disorders (e.g. Crohn disease). In the present study, we investigated the possible involvement of NOD2/CARD15 in the pathology of CHD by i) analyzing the local expression of NOD2 in atherectomy versus healthy tissue (n = 5 each) using histochemical immunofluorescence and ii) by testing the three major functional CARD15 variants (R702W, G908R and 1007fs) for association with early-onset CHD in 900 German patients and 632 healthy controls. RESULTS: In atherectomy tissue of CHD patients, NOD2 was detected in inflammatory cells at the luminal sides of the lesions. However, the allele and genotype frequencies of the three major CARD15 polymorphisms did not differ between CHD patients and controls. CONCLUSION: The NOD2 up-regulation in atheroma lesions indicates an involvement of this protein in the pathology of CHD. Although NOD2 could be important in local immune response mechanisms, none of the analyzed CARD15 variants seem to play a significant role in the etiology of CHD.