Differential Sensory and Clinical Phenotypes of Patients With Chronic Widespread and Regional Musculoskeletal Pain

Marina M. Finnern; Dieter Kleinböhl; Herta Flor; Justus Benrath; Rupert Hölzl


Pain. 2020;162(1):56-70. 

In This Article

Abstract and Introduction


The differentiation of chronic primary pain syndromes into those with widespread vs regional musculoskeletal pain has been characterized by controversial discussions about common or distinct mechanisms and core clinical and sensory criteria. For example, the recent revision of fibromyalgia criteria has discarded sensory characteristics such as number of "tender points." This study examined empirical evidence related to this diagnostic shift and aimed to identify basic sensory-clinical pain phenotypes in patients with chronic local primary pain (chronic primary back pain [CBP]) and patients with chronic widespread primary pain (fibromyalgia syndrome). Combined sensory-clinical pain phenotypes of 185 patients with previous CBP and fibromyalgia syndrome diagnoses were derived by a stepwise data reduction through descriptive statistical, correlational, principal components and latent class analyses. Clusters were cross-validated by linear discriminant analysis. Four clusters of patients were identified, requiring 4 pressure pain sensitivity markers (number of sensitive tender and control points, pain intensity, and pressure pain threshold at the trapezius) and 2 clinical pain characteristics (pain regions and present pain intensity). Subsequent discriminant analysis revealed that 3 discriminant functions of pressure sensitivity markers sufficed to differentiate the clusters. These sensory-clinical phenotypes differed also in somatic symptoms and impairment but neither in psychopathology nor in psychosocial cofactors. The results highlight the relevance of sensory testing in combination with clinical pain assessment in chronic primary pain syndromes.


Distinguishing patients with chronic primary pain who show widespread pain from patients with localized primary pain such as chronic primary back pain (CBP) by clinical and sensory criteria is a matter of debate.[22,27,45,49,66] Recent revisions of the ACR criteria of fibromyalgia syndrome (FMS)[71–73] have centered on chronic widespread pain as core characteristic and abandoned the sensory criterion of enhanced pressure sensitivity in 11 "tender points" (TPs).[74] The current FMS diagnosis requires the presence of widespread pain plus a critical combination of the Widespread Pain Index (WPI = number of pain sites) and the Symptom Severity Scale (a composite of abdominal pain, unrefreshing sleep, fatigue, cognitive symptoms, and depression).[71] The combined Fibromyalgia Symptom Scale (FS; 0–31) discriminates patients with FMS from those with regional musculoskeletal pain at FS ≥12.[71] Validation studies of the revised criteria indicated that patients with FMS showed higher levels of clinical pain, disability, and psychological distress and are more sensitive to mechanical and heat stimuli.[54] The significance of these characteristics is not clear because of overlaps with the revised criteria and depression and related symptoms such as sleep disorders, which could be symptoms of a comorbid mental disorder rather than core characteristics of the pain disorder.[24] Moreover, sensory aspects may signify phenotypical subgroups with different pain mechanisms, eg, peripheral vs central sensitization to enhanced deep pain sensitivity in some patients.[46,50] The relevance of sensory aspects of the pain symptoms and the sensitivity to pressure stimulation in different body regions is suggested by the finding that TPs are often associated with myofascial trigger points of peripheral etiology.[20,21] Enhanced sensitivity to pressure pain of patients with FMS can be distributed to some degree across the whole body and may occur also in control points (CPs).[26,69] Patients with FMS are also hypersensitive to heat,[25] indicating generally enhanced nociceptive signaling.[22,32,36] Whether this would differentiate regional and widespread pain is not known.[55,64] This study examined the diagnostic significance of sensory changes by a cluster-analytic approach to identify subgroups of patients according to sensory-clinical pain phenotypes without the comorbidity components of the Symptom Severity Scale. The identified pain phenotypes were then compared with respect to comorbidity and other aspects including general chronicity, functionality, and psychological distress.

We hypothesized the following:

  1. The number of hypersensitive body sites reflects a generalized pressure hypersensitivity underlying widespread pain; specific TPs are not qualitatively different from CPs.

  2. FMS and CBP overlap substantially in spatial spread of pain as well as in pressure hypersensitivity. This might reflect intermediary subgroups which could be revealed by combined sensory and clinical phenotyping.

  3. Thus, patients with chronic musculoskeletal primary pain could be differentiated into several sensory phenotypes across FMS or CBP according to degree and spatial distribution of hypersensitivity to pressure pain.

  4. These sensory-clinical phenotypes identify discriminable subgroups without recourse to secondary comorbidity or psychosocial factors.

  5. Enhanced sensitivity to heat pain in addition to pressure could differentiate subgroups with generalized sensitization.