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Ain intensity was VAS 4.9. Sensory symptoms do not seem to be of clinical importance to the patients in subgroup 5 even though they reach a positive score on the painDETECT in 15 . This reveals, that a group of patients with clinically significant pain intensity exists whose pain experience is not adequately covered by the questions of the PD-Q. In conclusion, besides nociceptive pain mechanisms neuropathic components also play a key role in the pathophysiology of axial low back pain. Obviously, these mechanisms play in concert so that the investigating physician faces a mixed pain syndrome. The analysis of the different pain components may MedChemExpress PD-1/PD-L1 AN 3199 inhibitor 1 provide a basis to the most promising therapy.Co-morbiditiesBack pain patients show a high frequency of co-morbidities such as sleep disorders, depression and panic/anxiety disorders [17]. More specifically in patients with neuropathic back pain these disorders occur quite often [19,20]. Our data supports this finding, as a large group of the patients showed pathological sleeping behaviour and signs of depression or panic/anxiety. However, compared to large epidemiological studies on unselected back pain and radiculopathy patients or classical neuropathic pain syndromes (e.g. diabetic polyneuropathy) the axial low back pain cohort in this study complained to a lesser extent of these comorbidities [17,18,20].Cluster 1 N Depression (PHQ-9 values) Mild (5?) Moderate (10?9) Severe (20?7) Panic/anxiety disorder MOS-SS Sleep disturbance Optimal sleep Somnolence Sleep quantity (hours) Sleep adequacy doi:10.1371/journal.pone.0068273.t003 40.8 47.7 36.6 6.4 54.4 42.6 27.9 3.8 5.1Cluster 2Cluster 3Cluster 4Cluster 531.4 33.2 3.5 3.37.6 35.8 3.1 5.39.5 33.1 4.0 3.36.8 26.1 2.1 4.42.7 38.4 38.8 6.2 50.41.5 42.6 38.1 6.2 54.42.8 42.9 40.6 6.4 53.35.6 46.4 34.1 6.6 60.Sensory Profiles in Axial Low Back PainFigure 3. Differences in PD-Q scores after IVD-surgery. The piechart depicts the proportion of patients with and without IVD-surgery scoring “positive”, “unclear” or “negative” in the PD-Q. There are no significant differences between the respective groups (x2-Test, p = 0.2215). doi:10.1371/journal.pone.0068273.gBetween the clusters a consistent distribution of co-morbidities was not prevalent. It is notable that patients from cluster 5 experienced an almost normal sleep adequacy with close-tonormal values for sleep disturbance and somnolence. Besides, 35 of these patients did not reveal signs of depression, while only 23727046 2.1 suffered from a severe depression (see table 3). This is notable, because 15 score positive on the PD-Q while showing a sensory profile without discrimination between different items. Thus, treatment response differences between axial low back pain patients and other neuropathic pain syndromes may not solely be explained by differences in the prevalence of comorbidities.Also, sensory symptoms and co-morbidities are not the only variables which determine the response to analgesic treatments. The pharmacological response is also influenced by genetic susceptibility and psychological factors such as catastrophizing and expectation which were not assessed in the present investigations. Another methodological consideration may limit the results of our study and questionnaire-based studies in general: Despite good sensitivity and specificity of the PD-Q [17], the question remains whether the distinction between neuropathic and nociceptive symptom profiles truly represents the biological bac.Ain intensity was VAS 4.9. Sensory symptoms do not seem to be of clinical importance to the patients in subgroup 5 even though they reach a positive score on the painDETECT in 15 . This reveals, that a group of patients with clinically significant pain intensity exists whose pain experience is not adequately covered by the questions of the PD-Q. In conclusion, besides nociceptive pain mechanisms neuropathic components also play a key role in the pathophysiology of axial low back pain. Obviously, these mechanisms play in concert so that the investigating physician faces a mixed pain syndrome. The analysis of the different pain components may provide a basis to the most promising therapy.Co-morbiditiesBack pain patients show a high frequency of co-morbidities such as sleep disorders, depression and panic/anxiety disorders [17]. More specifically in patients with neuropathic back pain these disorders occur quite often [19,20]. Our data supports this finding, as a large group of the patients showed pathological sleeping behaviour and signs of depression or panic/anxiety. However, compared to large epidemiological studies on unselected back pain and radiculopathy patients or classical neuropathic pain syndromes (e.g. diabetic polyneuropathy) the axial low back pain cohort in this study complained to a lesser extent of these comorbidities [17,18,20].Cluster 1 N Depression (PHQ-9 values) Mild (5?) Moderate (10?9) Severe (20?7) Panic/anxiety disorder MOS-SS Sleep disturbance Optimal sleep Somnolence Sleep quantity (hours) Sleep adequacy doi:10.1371/journal.pone.0068273.t003 40.8 47.7 36.6 6.4 54.4 42.6 27.9 3.8 5.1Cluster 2Cluster 3Cluster 4Cluster 531.4 33.2 3.5 3.37.6 35.8 3.1 5.39.5 33.1 4.0 3.36.8 26.1 2.1 4.42.7 38.4 38.8 6.2 50.41.5 42.6 38.1 6.2 54.42.8 42.9 40.6 6.4 53.35.6 46.4 34.1 6.6 60.Sensory Profiles in Axial Low Back PainFigure 3. Differences in PD-Q scores after IVD-surgery. The piechart depicts the proportion of patients with and without IVD-surgery scoring “positive”, “unclear” or “negative” in the PD-Q. There are no significant differences between the respective groups (x2-Test, p = 0.2215). doi:10.1371/journal.pone.0068273.gBetween the clusters a consistent distribution of co-morbidities was not prevalent. It is notable that patients from cluster 5 experienced an almost normal sleep adequacy with close-tonormal values for sleep disturbance and somnolence. Besides, 35 of these patients did not reveal signs of depression, while only 23727046 2.1 suffered from a severe depression (see table 3). This is notable, because 15 score positive on the PD-Q while showing a sensory profile without discrimination between different items. Thus, treatment response differences between axial low back pain patients and other neuropathic pain syndromes may not solely be explained by differences in the prevalence of comorbidities.Also, sensory symptoms and co-morbidities are not the only variables which determine the response to analgesic treatments. The pharmacological response is also influenced by genetic susceptibility and psychological factors such as catastrophizing and expectation which were not assessed in the present investigations. Another methodological consideration may limit the results of our study and questionnaire-based studies in general: Despite good sensitivity and specificity of the PD-Q [17], the question remains whether the distinction between neuropathic and nociceptive symptom profiles truly represents the biological bac.

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