The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

We have compiled a comprehensive QST protocol as part of the German Research Network on Neuropathic Pain (DFNS) using well established tests for nearly all aspects of somatosensation. This protocol encompasses thermal as well as mechanical testing procedures. Our rationale was to test for patterns of sensory loss (small and large nerve fiber functions) or gain (hyperalgesia, allodynia, hyperpathia), and to assess both cutaneous and deep pain sensitivity. The practicality of the QST protocol was tested in 18 healthy subjects, 21-58 years, half of them female. All subjects were tested bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for the presence of paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64-Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus-response-functions for pinprick and dynamic mechanical allodynia (pain to light touch), and pain summation (wind-up ratio) using repetitive pinprick stimulation. The full protocol took 27+/-2.3 min per test area. The majority of QST parameters were normally distributed only after logarithmic transformation (secondary normalization) except for the frequency of paradoxical heat sensations, cold and heat pain thresholds, and for vibration detection thresholds. Thresholds were usually lowest over face, followed by hand, and then foot. Only thermal pain thresholds, wind-up ratio and vibration detection thresholds were not significantly dependent on the body region. There was no significant right-to-left difference for any of the QST parameters; left-to-right correlation coefficients ranged between 0.78 and 0.97, thus explaining between 61% and 94% of the variance. This study has shown that a complete somatosensory profile of one affected area and one unaffected control area, which will be necessary to characterize patients with a variety of diseases, can be obtained within 1 h. Case examples of selected patients illustrate the value of z-transformed QST data for an easy survey of individual symptom profiles.

Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible.

Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients. Although QST shares similarities with the quantitative assessment of hearing or vision, which is extensively used in clinical practice and research, it has not gained a large acceptance among clinicians for many reasons, and in significant part because of the lack of information about standards for performing QST, its potential utility, and interpretation of results. A consensus meeting was convened by the Neuropathic Pain Special Interest Group of the International Association for the Study of Pain (NeuPSIG) to formulate recommendations for conducting QST in clinical practice and research. Research studies have confirmed the utility of QST for the assessment and monitoring of somatosensory deficits, particularly in diabetic and small fiber neuropathies; the assessment of evoked pains (mechanical and thermal allodynia or hyperalgesia); and the diagnosis of sensory neuropathies. Promising applications include the assessment of evoked pains in large-scale clinical trials and the study of conditioned pain modulation. In clinical practice, we recommend the use QST for screening for small and large fiber neuropathies; monitoring of somatosensory deficits; and monitoring of evoked pains, allodynia, and hyperalgesia. QST is not recommended as a stand-alone test for the diagnosis of neuropathic pain. For the conduct of QST in healthy subjects and in patients, we recommend use of predefined standardized stimuli and instructions, validated algorithms of testing, and reference values corrected for anatomical site, age, and gender. Interpretation of results should always take into account the clinical context, and patients with language and cognitive difficulties, anxiety, or litigation should not be considered eligible for QST. When appropriate standards, as discussed here, are applied, QST can provide important and unique information about the functional status of somatosensory system, which would be complementary to already existing clinical methods.

Some patients with myofascial pain from temporomandibular disorders (TMD) report pain in extra-trigeminal body regions. Our aim was to distinguish TMD as regional musculoskeletal pain syndrome (n=23) from a widespread pain syndrome (FMS; n=18) based on patients' tender point scores, pain drawings and quantitative sensory testing (QST) profiles. Referenced to 18 age- and gender-matched healthy subjects significant group differences for cold, pressure and pinprick pain thresholds, suprathreshold pinprick sensitivity and mechanical detection thresholds were found. Pain sensitivity in TMD patients ranged between those of FMS patients and healthy controls. The group of TMD patients was inhomogeneous with respect to their tender point count with an insensitive group (n=12) resembling healthy controls and a sensitive TMD group (n=9) resembling FMS patients. Nevertheless sensitive TMD patients did not fulfil diagnostic criteria for FMS in regard to widespread pain as shown by their pain drawings. TMD subgroups did not differ with respect to psychological parameters. The sensitive subgroup was more sensitive compared to healthy controls and to insensitive TMD patients in regard to their QST profile over all test areas as well as to their tenderness over orofacial muscles and trigeminal foramina. However, sensitive TMD patients had a short pain duration arguing against a transition from TMD to FMS over time. Data rather suggest an overlap in pathophysiology with FMS, e.g. a disturbance of central pain processing, in this subgroup of TMD patients. Those patients could be identified on the basis of their tender point count as an easy practicable screening tool.