Characterization of chronic pain and somatosensory function in spinal cord injury subjects

The pathophysiology of the chronic pain following spinal cord injury (SCI) is unclear. In order to study it's underlying mechanism we characterized the neurological profile of SCI subjects with (SCIP) and without (SCINP) chronic pain. Characterization comprised of thermal threshold testing for warmth, cold and heat pain and tactile sensibility testing of touch, graphesthesia and identification of speed of movement of touch stimuli on the skin. In addition, spontaneously painful areas were mapped in SCIP and evoked pathological pain--allodynia, hyperpathia and wind-up pain evaluated for both groups. Both SCIP and SCINP showed similar reductions in both thermal and tactile sensations. In both groups thermal sensations were significantly more impaired than tactile sensations. Chronic pain was present only in skin areas below the lesion with impaired or absent temperature and heat-pain sensibilities. Conversely, all the thermally impaired skin areas in SCIP were painful while painfree areas in the same subjects were normal. In contrast, chronic pain could be found in skin areas without any impairment in tactile sensibilities. Allodynia could only be elicited in SCIP and a significantly higher incidence of pathologically evoked pain (i.e. hyperpathia and wind-up pain) was seen in the chronic pain areas compared to SCINP. We conclude that damage to the spinothalamic tract (STT) is a necessary condition for the occurrence of chronic pain following SCI. However, STT lesion is not a sufficient condition since it could also be found in SCINP. The abnormal evoked pain seen in SCIP is probably due to neuronal hyperexcitability in these subjects. The fact that apparently identical sensory impairments manifest as chronic pain and hyperexcitability in one subject but not in another implies that either genetic predisposition or subtle differences in the nature of spinal injury determine the emergence of chronic pain following SCI.     

Quantitative sensory testing: a comprehensive protocol for clinical trials.

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.     

Quantitative somatosensory testing of subjects with chronic post-traumatic headache: Implications on its mechanisms

BackgroundChronic headache is one of the most prominent symptoms among subjects with traumatic head injury (THI). Despite the relatively high prevalence of chronic post-traumatic headache (CPTHA) and its enormous effect on the already poor quality of life of subjects with THI, its mechanisms has not been studied in depth.ObjectiveTo conducted quantitative somatosensory testing in THI subjects with and without chronic post-traumatic headache (CPTHA) in order to shed light on the yet, unknown pathophysiology of CPTHA.MethodsTHI subjects with and without CPTHA and healthy controls underwent thermal and mechanical threshold measurements in painful and pain-free regions in the head and in their hands (a remote pain-free region) and filled out and the post-traumatic stress disorder (PTSD) inventory. In addition, the THI and CPTHA filled out the Mc’Gill pain questionnaire (MPQ).ResultsTHI subjects with CPTHA had significantly higher thermal thresholds in both the head and hand indicating central damage to the pain and temperature system and in addition, a significantly lower pressure-pain threshold in the head as well as more severe PTSD symptomatology than the pain-free THI subjects and healthy controls.ConclusionsThe sensory profile of subjects with CPTHA suggests that CPTHA may be a form of central pain. The cranial mechanical hyperalgesia may originate from peripheral tissue damage accompanying the THI. Psychological factors may contribute to the development, and maintenance of CPTHA in susceptible individuals.     

Heterotopic noxious conditioning stimulation (HNCS) reduced the intensity of spontaneous pain, but not of allodynia in painful peripheral neuropathy.

In 15 patients with painful peripheral neuropathy and dynamic mechanical allodynia, the influence of spontaneous ongoing neuropathic pain on pain sensitivity in a remote pain-free area was examined, as was the influence of ischemia-induced heterotopic noxious conditioning stimulation (HNCS) on the intensity of ongoing pain and brush-evoked allodynia. In addition, the modulating effect of HNCS on pain sensitivity in a pain-free area was investigated. Pain thresholds to pressure and heat as well as the sensitivity to suprathreshold pressure- and heat pain were assessed in the pain-free area. Dynamic mechanical allodynia was induced by a recently developed semi-quantitative brushing technique and the patients continuously rated the intensity of the allodynia using a computerized visual analogue scale (VAS). The total brush-evoked pain intensity was calculated as the area under the VAS curve. At baseline, no significant difference in pain sensitivity was found between patients and their healthy controls in the pain-free area, indicating a lack of activation of pain modulatory systems from the spontaneous pain. Compared to baseline, the patients rated the ongoing neuropathic pain intensity significantly lower during the HNCS-procedure (p<0.05). In contrast, there was no influence from HNCS on the total brush-evoked pain intensity. In the pain-free area higher pressure pain thresholds were demonstrated during conditioning stimulation in patients and controls alike (p<0.01). In controls only, a significantly higher heat pain threshold was found during the HNCS-procedure (p<0.01). The main finding of the present study was that HNCS altered differentially spontaneous and brush-provoked pain in patients with painful peripheral neuropathy.     

Somatosensory perception and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from rheumatoid arthritis.

The purpose was to investigate the influence of ongoing pain from an inflammatory nociceptive pain with two different disease durations on somatosensory functions and the effect of heterotopic noxious conditioning stimulation (HNCS) on 'diffuse noxious inhibitory controls' (DNIC) related mechanisms. Eleven patients with rheumatoid arthritis of a short duration (<1 year) (RA1), and 10 patients with rheumatoid arthritis of longer duration (>5 years) (RA5) as well as 21 age- and sex-matched healthy controls participated. Pressure pain sensitivity, low threshold mechanoreceptive function and thermal sensitivity, including thermal pain, were assessed over a painful and inflamed joint as well as in a pain-free area, i.e. the right thigh before HNCS (cold-pressor test) and repeated at the thigh only during and following HNCS. In RA1 and RA5 allodynia to pressure was seen over the joint (p<0.02 and p<0.001 respectively) in conjunction with hypoaesthesia to light touch (p<0.02) and hyperaesthesia to innocuous cold (p<0.05) in RA5. At the thigh, allodynia to pressure was found in RA5 (p<0.002). During HNCS, the sensitivity to pressure pain decreased in patients and controls alike (p<0.001). In conclusion, over an inflamed joint allodynia to pressure was found in both RA groups, with additional sensory abnormalities in RA5. In a non-painful area, allodynia to pressure was found in RA5, suggesting altered central processing of somatosensory functions in RA5 patients. The response to HNCS was similar in both RA groups and controls, indicating preserved function of DNIC-related mechanisms.     

Hemiplegic shoulder pain: Evidence of a neuropathic origin

Hemiplegic shoulder pain (HSP) is common after stroke. Whereas most studies have concentrated on the possible musculoskeletal factors underlying HSP, neuropathic aspects have hardly been studied. Our aim was to explore the possible neuropathic components in HSP, and if identified, whether they are specific to the shoulder or characteristic of the entire affected side. Participants included 30 poststroke patients, 16 with and 14 without HSP, and 15 healthy controls. The thresholds of warmth, cold, heat-pain, touch, and graphesthesia were measured in the intact and affected shoulder and in the affected lower leg. They were also assessed for the presence of allodynia and hyperpathia, and computed tomography/magnetic resonance imaging scans of the brain were reviewed. In addition, chronic pain was characterized. Participants with HSP exhibited higher rates of parietal lobe damage (P < 0.05) compared to those without HSP. Both poststroke groups exhibited higher sensory thresholds than healthy controls. Those with HSP had higher heat-pain thresholds in both the affected shoulder (P < 0.001) and leg (P < 0.01), exhibited higher rates of hyperpathia in both these regions (each P < 0.001), and more often reported chronic pain throughout the affected side (P < 0.001) than those without HSP. The more prominent sensory alterations in the shoulder region suggest that neuropathic factors play a role in HSP. The clinical evidence of damage to the spinothalamic-thalamocortical system in the affected shoulder and leg, the presence of chronic pain throughout the affected side, and the more frequent involvement of the parietal cortex all suggest that the neuropathic component is of central origin.     

Depression and changed pain perception: hints for a central disinhibition mechanism

Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n=20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). In depressive disorder (to a lesser extent also in FMS), significantly decreased cold pain thresholds and an increased wind-up were found, although the mechanical pain thresholds and pain sensitivity were comparable to those of the healthy controls. All the detection thresholds were within the normal range in all the groups. In depressive disorder, there were no significant side differences in the detection and pain thresholds. The results contradict the former assumption of a general insensitivity to experimental pain in depressive disorder. In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.     

Heterogeneous sensory processing in persistent postherniotomy pain

Previous studies on sensory function in persistent postherniotomy pain (PPP) have only identified pressure pain threshold to be significantly different from pain-free patients despite several patients reporting cutaneous pain and wind-up phenomena. However the limited number of patients studied hinders evaluation of potential subgroups for further investigation and/or treatment allocation. Thus we used a standardized QST protocol to evaluate sensory functions in PPP and pain-free control patients, to allow individual sensory characterization of pain patients from calculated Z-values. Seventy PPP patients with pain related impairment of everyday activities were compared with normative data from 40 pain-free postherniotomy patients operated >1 year previously. Z-values showed a large variation in sensory disturbances ranging from pronounced detection hypoesthesia (Z = 6, cold) to pain hyperalgesia (Z = −8, pressure). Hyperalgesia for various modalities were found in 80% of patients, with pressure hyperalgesia in ∼65%, and cutaneous (mechanical or thermal) hyperalgesia in ∼35% of patients. The paradoxical combination of tactile hypoesthesia and hyperalgesia was seen in ∼25% of patients. Increased pain from repetitive tactile and/or brush stimulation was found in 51%, suggesting a role of altered central nociceptive function in this subpopulation. A high incidence (26%) of pressure hyperalgesia was found in the contralateral groin, with a significant correlation (rho = 0.58, p = 0.002) to the hyperalgesic level on the painful side, again suggesting central nervous mechanisms in PPP. In conclusion, this study shows that a standardized trauma results in heterogeneous combinations of hypo- and hyperalgesia. Z-score evaluation of sensory function identifies subpopulations in PPP, which may be used in selecting surgical and/or pharmacological treatment strategies.     

Somatosensory perception in a remote pain-free area and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from long-term trapezius myalgia.

In patients with localized musculoskeletal pain, spread of pain and tenderness outside the primarily painful area and sometimes even generalization of pain have been reported, the latter possibly indicating a dysfunction of endogenous pain modulatory systems. The purpose of the study was to use patients with long-term trapezius myalgia as a model to investigate the possible influence of a localized muscle pain on somatosensory processing in a remote pain-free area and the effect of heterotopic noxious conditioning stimulation (HNCS) on 'diffuse noxious inhibitory controls' (DNIC) related mechanisms. Altered somatosensory processing may indicate subclinical derangement of endogenous modulatory systems. Ten patients with long-term (> or = 1 year) trapezius myalgia and 10 age- and sex-matched healthy controls participated. Pressure pain sensitivity, low threshold mechanoreceptive function and thermal sensitivity, including thermal pain, were assessed at the right thigh before, during and following HNCS. Pain was induced in the forearm by the tourniquet test. At rest allodynia to pressure was found at the thigh in conjunction with hypoaesthesia to cold (p<0.03 and p<0.01 respectively), in patients compared with controls. During HNCS, the sensitivity to pressure pain and suprathreshold heat pain decreased in patients and controls alike (p<0.02 and p<0.04 respectively) and returned to baseline following HNCS. In conclusion, in a remote non-painful area allodynia to pressure and hypoaesthesia to cold were found in conjunction with preserved function of DNIC-related mechanisms. Whether altered central somatosensory processing at rest may indicate a predisposition for further spread of pain is at present unclear.     

The Osteoarthritis Knee Model: Psychophysical Characteristics and Putative Outcomes

The knee osteoarthritis (KOA) model is a convenient and coherent archetype that is frequently used in pharmaceutical trials of drugs with analgesic and/or anti-inflammatory properties; yet, little is known about its specific pathophysiology. The presumed chronic inflammatory etiology of osteoarthritis suggests that nociceptive processes and neurogenic inflammation predominate in this condition. However, most chronic pain conditions are associated with changes in peripheral and central processing. Recent data corroborate this as an important mechanism in KOA. We compared psychophysical characteristics (including thermal Quantitative Sensory Testing); thermal, mechanical, and functional wind-up; thermal and mechanical aftersensations; and pressure algometry of 37 subjects with KOA with 35 age- and sex-matched controls. A third of the KOA subjects demonstrated hypoesthesia to vibration and the 4.56 von Frey fiber, yet few showed allodynia in their worse knee. The majority of subjects had abnormalities to pinprick (41% were hyperalgesic and 27% were hypoesthetic). Compared to controls, the more painful knee was hypoesthetic to cold detection and had greater thermal wind-up, lower pressure-pain thresholds, thermal and mechanical aftersensations, and twice the pain ratings of controls after stair climb. Substantial intraindividual differences were found in KOA subjects and controls for mechanical wind-up and algometric thresholds.PerspectiveThese results develop the KOA model and suggest mechanistic hypotheses. Certain of these tests may ultimately prove to be responsive, quasi-objective, and quantitative outcomes for research and lend empirical support to the notion of measurable sensitization in osteoarthritis.     

Predictors of clinical pain intensity in patients with fibromyalgia syndrome

Central changes in pain processing have been previously reported in patients with fibromyalgia syndrome. These changes include decreased thresholds to mechanical and thermal stimuli (allodynia) and central sensitization, both of which are fundamental to the generation of clinical pain. Therefore, psychophysical measures of central pain processing may be useful predictors of clinical pain intensity of fibromyalgia syndrome patients. Previous studies of fibromyalgia syndrome patients have shown statistically significant correlations of psychophysical test results with clinical pain intensity. The tests used to characterize this important relationship were dependent on spinal cord pain mechanisms and included temporal summation of pain or wind-up and wind-up after-sensations. Particularly, the magnitude of wind-up after-sensations appeared to be one of the best predictors for clinical pain intensity of fibromyalgia syndrome patients (27%). Furthermore, the combination of tender point count, negative affect, and wind-up aftersensations accounted for approximately 50% of the variance in clinical pain intensity of fibromyalgia syndrome patients. Therefore, wind-up after-sensations, tender point count, and negative affect not only seem to represent relevant pain mechanisms but also strongly emphasize their importance for fibromyalgia syndrome pain.     

Modality-specific sensory changes in humans after the induction of long-term potentiation (LTP) in cutaneous nociceptive pathways

The impact of long-term potentiation (LTP) in nociceptive pathways on somatosensory perception was examined by means of quantitative sensory testing (QST) in the ventral forearm of 12 healthy human subjects. Electrical high-frequency stimulation of the forearm skin (HFS; 5 x 1 s at 100 Hz and 10 x detection threshold) led to an abrupt increase of pain to single electrical test stimuli, which were applied through the same electrode (perceptual LTP +72%, p<0.01). Perceptual LTP outlasted the 1-h observation period. The effects of HFS on somatosensory perception of natural test stimuli in the conditioned skin area were restricted to mechanical submodalities. Subjects exhibited a significant decrease of pain threshold and an increase of pain ratings to suprathreshold pinprick stimuli (p<0.01). In 5 out of 12 subjects (42%) light tactile stimuli led to painful sensations (dynamic mechanical allodynia). Furthermore, a small but significant decrease of threshold to blunt pressure stimuli (p<0.05) was found. In contrast, all thermal modalities comprising cold and warm detection thresholds, cold and heat pain thresholds as well as pain summation (perceptual wind up) remained unaltered. These data show that HFS of peptidergic cutaneous C-fiber afferents predominantly modulates Adelta- and Abeta-fiber mediated somatosensory functions, suggesting that LTP in nociceptive pathways enhances human pain sensitivity via interaction of two afferent pathways (extrinsic sensitization).     

Somatosensory abnormalities in atypical odontalgia: A case-control study

Somatosensory function in patients with persistent idiopathic types of orofacial pain like atypical odontalgia (AO) is not well described. This study tested the hypothesis that AO patients have significantly more somatosensory abnormalities than age- and sex-matched controls. Forty-six AO patients and 35 controls participated. Inclusion criteria for AO were pain in a region where a tooth had been endodontically or surgically treated, persistent pain >6 months, and lack of clinical and radiological findings. The examination included qualitative tests and a battery of intraoral quantitative sensory testing (QST). Most AO patients (85%) had qualitative somatosensory abnormality compared with few controls (14%). The most common qualitative abnormalities in AO patients were found with pin-prick 67.4%, cold 47.8%, and touch 46.5% compared with 11.4%, 8.6%, and 2.9%, respectively, in the control group (P<0.001). Between-group differences were seen for many intraoral QST: mechanical detection threshold, mechanical pain threshold (pinprick), dynamic mechanical allodynia (brush), dynamic mechanical allodynia (vibration), wind-up ratio, and pressure pain threshold (P<0.01). In the trigeminal area, between-group differences in thermal thresholds were nonsignificant while differences in cold detection at the thenar eminence were significant. Individual somatosensory profiles revealed complex patterns with hyper- and hyposensitivity to intraoral QST. Between-group differences in pressure pain thresholds (P<0.02) were observed at the thenar eminence. In conclusion, significant abnormalities in intraoral somatosensory function were observed in AO, which may reflect peripheral and central sensitization of trigeminal pathways. More generalized sensitization of the nociceptive system may also be part of AO pathophysiology.     

Pain and somatosensory findings in patients 3 years after total hip arthroplasty

Background: Chronic hip pain after total hip arthroplasty (THA) is a significant problem, but the aetiology remains unclear. Aims: To determine sensory function in patients with chronic hip pain 3 years after THA. Patients without hip pain after THA served as controls. Methods: Eighteen patients with chronic hip pain and 18 controls without chronic hip pain were recruited from a previous questionnaire study about hip pain after total hip arthroplasty. All participants answered questions about pain and mental vulnerability and underwent clinical examination followed by quantitative sensory testing (brush‐evoked allodynia, pinprick hyperalgesia, mechanical and thermal thresholds). Results: Brush‐evoked allodynia was present in 4 patients with hip pain (P=0.1) and pinprick hyperalgesia (P=0.02) was more frequent in patients with chronic hip pain. Mechanical and thermal thresholds were similar in patients and controls. Patients with chronic hip pain had higher scores on the mental vulnerability scale (P<0.001). Chronic hip pain was significantly associated with low back pain (P=0.002). Conclusions: We found signs of hypersensitivity on the operated side, which was more prominent in patients with pain. Pain referred from the back or deeper structures in the hip seems to play a role for the pain in subgroups of patients. In addition, chronic hip pain was associated with mental vulnerability.     

Evidence of persistent central sensitization in chronic headaches: a multi-method study

The aim of this study was to investigate central sensitization (CS) in chronic headaches and compare this phenomenon between chronic migraine (CM) and chronic tension-type headache (CTTH). We recruited 69 patients with chronic headaches and 18 control subjects. Questionnaires of headache history, allodynia and the Hospital Anxiety and Depression scale were administered. We recorded thresholds for pinprick and pressure pain, blink (BR) and nociceptive flexion reflex (NFR) R3 component coupled with wind-up ratios. Thresholds for pressure and pinprick pain, BR and NFR R3 were lower and wind-up ratios higher in patients. No differences of CS parameters between CM and CTTH were observed. CS is persistent and prevalent in patients with various types of chronic headache. CS levels are unrelated to the predominant side of pain, disease duration or depression. Neither is CS related to the headache type, suggesting similar mechanisms of headache chronification and chronicity maintaining and possibly explaining clinical similarity of various forms of chronic headache.     

Sad mood increases pain sensitivity upon thermal grill illusion stimulation: implications for central pain processing

In different fields of neuroscience research, illusions have successfully been used to unravel underlying mechanisms of stimulus processing. One such illusion existing for the field of pain research is the so-called thermal grill illusion. Here, painful sensations are elicited by interlacing warm and cold bars, with stimulus intensities (temperatures) of these bars being below the respective heat pain or cold pain thresholds. To date, the underlying mechanisms of this phenomenon are not completely understood. There is some agreement, however, that the sensation evoked by this stimulation is generated by central nervous interactions. Therefore, we followed two approaches in this study: firstly, we aimed at developing and validating a water-driven device which might be used in fMRI scanners in future studies - subject to minor adaptations. Secondly, we aimed to interfere with this illusion by induction of a sad mood state, a procedure which is suggested to influence central nervous structures that are also involved in pain processing.The newly developed device induced thermal grill sensations similar to those reported in the literature. Induction of sad, but not neutral mood states, resulted in higher pain and unpleasantness ratings of the painful illusion. These findings might be of importance for the understanding of pain processing in healthy volunteers, but putatively even more so in patients with major depressive disorder. Moreover, our results might indicate that central nervous structures involved in the affective domain or cognitive domain of pain processing might be involved in the perception of the illusion.     

Mechanical and heat hyperalgesia highly predict clinical pain intensity in patients with chronic musculoskeletal pain syndromes

Multiple abnormalities in pain processing have been reported in patients with chronic musculoskeletal pain syndromes. These changes include mechanical and thermal hyperalgesia, decreased thresholds to mechanical and thermal stimuli (allodynia), and central sensitization, all of which are fundamental to the generation of clinical pain. Therefore, we hypothesized that quantitative sensory tests may provide useful predictors of clinical pain intensity of such patients. Our previous studies of fibromyalgia (FM) patients have shown statistically significant correlations of quantitative sensory test results with clinical pain intensity, including mechanical spatial summation, number of pain areas, wind-up, and wind-up aftersensations. Although these tests predicted up to 59% of the variance in FM clinical pain intensity, their expense and technical complexities limited widespread use in clinical practice and trials. Thus, we developed practical tests of primary (mechanical) and secondary (heat) hyperalgesia that also strongly predict clinical pain intensity in patients with chronic musculoskeletal pain disorders. Thirty-six individuals with FM, 24 with local musculoskeletal pain, and 23 normal controls underwent testing of mechanical and heat hyperalgesia at the shoulders and hands. All subjects rated experimental pains using an electronic visual analog scale. Using either heat or pressure pain ratings as well as tender point counts and negative affect as predictors, up to 49.4% of the patients' variance of clinical pain intensity could be estimated. Results of this study emphasize the important contributions of peripheral and central factors to both local and widespread chronic pain. Overall, measures of mechanical and heat hyperalgesia in combination with tender point and negative affect provided powerful predictors of clinical pain intensity in chronic musculoskeletal pain patients that can be readily used in clinical practice and trials. PERSPECTIVE: Simple tests of mechanical and heat hyperalgesia can predict large proportions of the variance in clinical pain intensity of chronic musculoskeletal pain patients and thus are feasible to be included in clinical practice and clinical trials.     

Disruption of thermal perception in a multiple sclerosis patient with central pain

OBJECTIVE: To investigate integrative thermal perception in a patient with multiple sclerosis. DESIGN: Quantitative thermosensory testing was used to evaluate pain and other sensations produced by heat, cold, and the thermal grill pain illusion. PATIENT: The authors report on a 43-year-old patient with central pain manifest most strongly in her left arm and hand, contralateral to an upper cervical spinothalamic lesion due to multiple sclerosis. OUTCOME MEASURES AND RESULTS: Quantitative thermosensory testing showed that the patient had heat hypalgesia (no pain with stimuli of 45-50 degrees C) and cold allodynia (pain with innocuous cool temperatures, 25-10 degrees C). Whereas healthy subjects rated 20 degrees and 40 degrees C as nonpainful, but the thermal grill (intermixed 20 and 40 degrees C stimuli) as painful, the patient rated the thermal grill as less painful than 20 degrees C. CONCLUSIONS: The absence of thermal grill-evoked pain is consistent with the hypothesis that in some cases of central pain the loss of the thermosensory pathway results in disruption of the normal cold inhibition of burning pain.     

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values

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.