Differentiation of pain ratings in combat-related posttraumatic stress disorder

Although posttraumatic stress disorder (PTSD) is associated with chronic pain, preliminary evidence suggests reduced experimental pain sensitivity in this disorder. The questions addressed in the present study were whether pain perception would also be reduced in PTSD patients who are not suffering from chronic pain symptoms, and whether a reduction in pain sensitivity would also be present in combat veterans who did not develop PTSD. For this, we determined thermal detection and pain thresholds in 10 male combat-related PTSD patients, 10 combat control subjects (no PTSD) and 10 healthy controls without combat experience. All subjects were pain free. First, we measured thermal sensory thresholds with ramped heat and cold stimuli using the method of limits. Ramped thermal sensory stimulation revealed no deficits for the detection of (non-noxious) f2.1thermal stimuli between groups. In contrast, heat and cold pain thresholds in both combat groups (PTSD and combat controls) were significantly increased compared to healthy controls. However, these stimuli could not distinguish between the two groups due to ceiling effects. When using longer-lasting heat stimulation at different temperatures (30 s duration; method of fixed stimuli), we found significantly lower frequency of pain reports in PTSD patients compared with both combat and healthy controls, as well as significantly lower pain ratings. Our results suggest an association of PTSD with reduced pain sensitivity, which could be related to PTSD-related (neuro-)psychological alterations or to a pre-existing risk factor for the disorder.     

Inhibition of c-Kit signaling is associated with reduced heat and cold pain sensitivity in humans

The tyrosine kinase receptor c-Kit is critically involved in the modulation of nociceptive sensitivity in mice. Ablation of the c-Kit gene results in hyposensitivity to thermal pain, whereas activation of c-Kit produces hypersensitivity to noxious heat, without altering sensitivity to innocuous mechanical stimuli. In this study, we investigated the role of c-Kit signaling in human pain perception. We hypothesized that subjects treated with Imatinib or Nilotinib, potent inhibitors of tyrosine kinases including c-Kit but also Abl1, PDFGFRα, and PDFGFRβ, that are used to treat chronic myeloid leukemia (CML), would experience changes in thermal pain sensitivity. We examined 31 asymptomatic CML patients (14 male and 17 female) receiving Imatinib/Nilotinib treatment and compared them to 39 age- and sex-matched healthy controls (12 male and 27 female). We used cutaneous heat and cold stimulation to test normal and noxious thermal sensitivity, and a grating orientation task to assess tactile acuity. Thermal pain thresholds were significantly increased in the Imatinib/Nilotinib-treated group, whereas innocuous thermal and tactile thresholds were unchanged compared to those in the control group. In conclusion, our findings suggest that the biological effects of c-Kit inhibition are comparable in mice and humans in that c-Kit activity is required to regulate thermal pain sensitivity but does not affect innocuous thermal and mechanical sensation. The effect on experimental heat pain observed in our study is comparable to those of several common analgesics; thus modulation of the c-Kit pathway can be used to specifically modulate noxious heat and cold sensitivity in humans.     

Hypersensitivity to pain in congenital blindness

Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. We also assessed detection thresholds for innocuous warmth and cold, and participants’ attitude toward painful encounters in daily life. Our results show that, compared to sighted subjects, congenitally blind subjects have lower heat pain thresholds, rate suprathreshold heat pain stimuli as more painful, and have increased sensitivity for cold pain stimuli. Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing.     

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease

Patients with Parkinson’s disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P < .001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P < .02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P < .02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities.     

Do burn injuries during infancy affect pain and sensory sensitivity in later childhood?

Studies in animals and humans suggest that neonatal and early infant pain or stress experiences can induce long-term alterations in somatosensory and pain processing. We studied pain and sensory sensitivity in school-aged children (9–16 years) who had suffered moderate (N = 24) or severe (N = 24) burn injuries in infancy (6–24 months of age) and 24 controls. Quantitative sensory testing entailing detection and pain thresholds for thermal and mechanical stimuli and perceptual sensitization to tonic heat and repetitive mechanical stimuli was performed. Two testing sites (thenar, trigeminal region), both not affected by the burn injury, were used to determine whether there are global changes in pain sensitivity. The result pattern suggests a differential impact of burn severity. Compared to controls, moderately burned children showed significantly higher mechanical detection thresholds (thenar) and significantly lower mechanical pain thresholds and significantly greater perceptual sensitization to repetitive mechanical stimuli (both testing sites). No significant alterations were observed for thermal stimuli. In contrast, severely burned children showed, compared to controls, primarily alterations in thermal pain sensitivity (elevated pain thresholds at both testing sites, significantly greater perceptual sensitization at the thenar). In these children, mechanical pain sensitivity and detection thresholds were not consistently altered. This differential pattern of altered sensory and pain sensitivity may reflect differences in experienced stress, pain and analgesic treatment between moderately and severely burned children. Most importantly, our findings suggest that early traumatic and painful injuries, such as burns, can induce global, long-term alterations in sensory and pain processing.     

Increased pain sensitivity in alcohol withdrawal syndrome

Withdrawal from analgesic and addictive substances such as opioids or ethanol is associated with increased sensitivity to sensory stimulation in animal models. Here, we investigated perception of innocuous and noxious thermal or electric stimuli applied to the left hand or sternum in 30 male patients undergoing withdrawal from alcohol, 30 male abstained alcoholics and matched controls. The alcohol withdrawal scale and the Banger score were obtained to estimate the severity of withdrawal. In addition, the Beck depression inventory was used to estimate the influence of depressive symptoms on pain perception. The data presented provide substantial evidence that subjects undergoing alcohol withdrawal show increased heat pain sensitivity. Interestingly, this effect was observed both on the left hand and sternum. Pain thresholds and tolerances of electric stimuli did not differ between groups. However, in a subgroup analysis, a higher sensitivity for electrical pain thresholds and tolerances was observed in those patients that were identified to require pharmacological treatment for withdrawal according to disease severity. Furthermore, the perceived painful thermal and electrical sensation was substantially influenced by the affective state of patients. No differences were found between patients of the abstained group and control subjects for any pain parameter. In conclusion, we demonstrate withdrawal‐induced hyperalgesia upon thermal stimulation in patients. Since the influence of affective symptoms on pain perception during withdrawal is remarkable, we assume that peripheral and central mechanisms might account for this finding, which should be assessed in detail in future studies.     

Thermal pain perception after aerobic exercise

OBJECTIVE: To examine thermal pain perception before, 5 minutes after, and 30 minutes after 30 minutes of treadmill exercise at 75% of maximal oxygen uptake (V o 2 max). DESIGN: Repeated-measures. SETTING: Sports science laboratory. PARTICIPANTS: Convenience sample of 14 healthy male and female volunteers (mean age +/- standard deviation, 32+/-3y). INTERVENTIONS: Sensory thresholds, pain thresholds, and pain ratings to hot and cold stimuli were measured before and after 30 minutes of treadmill exercise at 75% of V o 2 max. The hot and cold stimuli were delivered by using a thermode placed on the thenar eminence of the nondominant hand. Thermal sensory and pain thresholds were determined during continuous ramps in temperature of the thermode. MAIN OUTCOME MEASURES: Pain ratings were measured on a visual analog scale at 10-second intervals over 2 minutes of thermal pain stimulation. RESULTS: There were no significant changes in thermal sensitivity, pain thresholds, or pain ratings for either heat or cold after 30 minutes of exercise at 75% of V o 2 max. CONCLUSIONS: Pain perception to thermal stimuli was unaltered after 30 minutes of exercise at 75% of V o 2 max, an intensity and duration of exercise previously shown to alter pain perception to electric and mechanical stimuli.     

Sensory abnormalities and pain in Parkinson disease and its modulation by treatment of motor symptoms

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain in PD and to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain in PD and the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms. PD patients have altered sensory and pain thresholds in the off‐medication state. Both levodopa and DBS improve motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non‐motor symptoms do not necessarily share the same mechanisms. Whether dopamine and DBS have a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism‐based approach to pain in PD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related to PD before specific treatment can be instituted.     

Vulvar vestibulitis severity--assessment by sensory and pain testing modalities

Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Previous quantitative sensory test (QST) studies have demonstrated reduced vestibular pain thresholds in these patients. Here we try to find whether QST findings correlate to disease severity. Thirty-five vestibulitis patients, 17 with moderate and 18 with severe disorder, were compared to 22 age matched control women. Tactile and pain thresholds for mechanical pressure and thermal pain were measured at the posterior fourcette. Magnitude estimation of supra-threshold painful stimuli were obtained for mechanical and thermal stimuli, the latter were of tonic and phasic types. Pain thresholds were lower and supra-threshold magnitude estimations were higher in VVS patients, in agreement with disease severity. Cut-off points were defined for results of each test, discriminating between moderate VVS, severe VVS and healthy controls, and allowing calculation of sensitivity and specificity of the various tests. Our findings show that the best discriminative test was mechanical pain threshold obtained by a simple custom made 'spring pressure device'. This test had the highest kappa value (0.82), predicting correctly 88% of all VVS cases and 100% of the severe VVS cases. Supra-threshold pain magnitude estimation for tonic heat stimulation also had a high kappa value (0.73) predicting correctly 82% overall with a 100% correct diagnosis of the control group. QST techniques, both threshold and supra-threshold measurements, seem to be capable of discriminating level of severity of this clinical pain syndrome.     

Cortical thickness correlates of pain and temperature sensitivity

It is well established that there is individual variability in pain and temperature sensitivity. Functional brain imaging studies have found that interindividual heat pain variability correlates with brain activity in sensory and pain modulation areas. Thus, it is possible that these individual differences are associated with variability in gray matter thickness of cortical regions involved in thermoreception and pain. To test this, we investigated the relationship between thermal thresholds and cortical thickness in 80 healthy subjects. Subjects underwent a psychophysical session to determine their cool detection (CD), warm detection (WD), cold pain (CP), and heat pain (HP) threshold. A high-resolution structural magnetic resonance imaging scan was acquired for each subject. We correlated each threshold measure to cortical thickness of regions associated with thermoreception and pain. The mean (± SD) thresholds were 30.7 °C (± 0.8) for CD, 33.8 °C (± 0.7) for WD, 11.7 °C (± 9.7) for CP, and 45.3 °C (± 2.8) for HP. The brain gray matter analysis revealed a strong correlation between greater thermal and pain sensitivity and cortical thickening of the primary somatosensory cortex. Additionally, greater sensitivity to cool stimuli correlated with cortical thickening in the paracentral lobule, and greater WD correlated with cortical thinning in the anterior midcingulate cortex. We also found that greater HP sensitivity correlated with thickening in the posterior midcingulate cortex and the orbitofrontal cortex. These cortical gray matter correlates of thermal and pain sensitivity provide a neural basis for individual differences in thermal sensitivity.     

Variation in quantitative sensory testing and epidermal nerve fiber density in repeated measurements

Quantitative sensory testing (QST) is commonly used to evaluate peripheral sensory function in neuropathic conditions. QST measures vary in repeated measurements of normal subjects but it is not known whether QST can reflect small changes in epidermal nerve fiber density (ENFd). This study evaluated QST measures (touch, mechanical pain, heat pain and innocuous cold sensations) for differences between genders and over time using ENFd as an objective-independent measure. QST was performed on the thighs of 36 healthy volunteers on four occasions between December and May. ENFd in skin biopsies was determined on three of those visits. Compared to men, women had a higher ENFd, a difference of 12.2 ENFs/mm. They also had lower tactile and innocuous cold thresholds, and detected mechanical pain (pinprick) at a higher frequency. Heat pain thresholds did not differ between genders. By the end of the 24-week study, men and women showed a small reduction (p < 0.05) in the frequency of sharp mechanical pain evoked by pinprick whereas tactile and thermal thresholds showed no change. This coincided with a small decrease in ENFd, 4.18 ENFs/mm. Variation in measurements over time was large in a fraction of normal subjects. We conclude that most QST measures detect relatively large differences in epidermal innervation (12.2 ENFs/mm), but response to mechanical pain was the only sensory modality tested with the sensitivity to detect small changes in innervation (4.18 ENFs/mm). Since some individuals had large unsystematic variations, unexpected test results should therefore alert clinicians to test additional locations.     

Test order of quantitative sensory testing facilitates mechanical hyperalgesia in healthy volunteers

Quantitative sensory testing (QST) has become a widely used method to evaluate different submodalities of the somatic sensory system (predominantly) in patients with neuropathic pain. QST consists of 7 tests measuring 13 parameters in order to assess and quantify the perception of temperature, touch, pain, pressure, and vibration. The German Research Network on Neuropathic Pain implemented a standardized QST protocol including a defined testing order of the measurements. Accordingly, subjects tested with QST undergo thermal before mechanical testing. In the present study, we investigated the effect of testing order on the results of QST. Twenty healthy subjects were tested twice, 1 week apart with 2 different QST testing orders: the standardized testing order according to the German Research Network on Neuropathic Pain and a modified testing order in which mechanical stimuli were applied before thermal stimuli. For the test protocol that began with thermal testing, subjects exhibited signs of an increased mechanical perception: The mechanical pain sensitivity was significantly increased (P = .001, Wilcoxon test) for each pinprick stimulator and the mechanical pain threshold was lowered by a factor of 2 when compared with the modified testing order in which mechanical parameters were tested at the beginning of the session without prior thermal stimulation. Thermal parameters were the same for both test-order paradigms. These data indicate that preceding mild thermal stimulation might lead to a sensitization to mechanical stimuli and thus to mechanical hyperalgesia. Alternative habituation mechanisms in the modified testing order resulting from repeated pinprick stimulation at the beginning should also be debated. QST is a helpful diagnostic tool but interpretation should be done with consideration of interaction between test parameters. Reference data are only valid in the testing order from which they are obtained. PERSPECTIVE: Present data showed that mechanical hyperalgesia followed thermal testing. This article demonstrates that the test order of quantitative sensory testing is relevant in interpreting the results obtained. Reference values are suitable in the test order from which they are obtained.     

Évaluation quantitative des troubles sensitifs et des douleurs neuropathiques

Quantitative sensory testing (QST) may be defined as the analysis of perception of pain in response to thermal and mechanical stimuli of measured intensity. This method uses thermal, mechanical and vibratory stimuli, enabling the measurement of pain thresholds and sensations caused by suprathreshold stimulation. QST can quantify hypoesthesia (raised detection thresholds), allodynia (lowered pain thresholds) and hyperalgesia (increased response to suprathreshold stimuli). It is suitable for detecting or monitoring peripheral polyneuropathies characterized by fine fiber impairment, particularly diabetic peripheral neuropathies. It has also been used to analyse the pathophysiological mechanisms involved in certain neuropathic pain conditions and to assess the effects of treatments for neuropathic pain. In this paper the relevance and limitations of QST for the assessment of neuropathic pain and its treatment are discussed.     

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 sensory testing in children with migraine: preliminary evidence for enhanced sensitivity to painful stimuli especially in girls

Recent studies showed an enhanced general sensitivity to painful stimuli in adult migraineurs during as well as between attacks. Yet, the influence of a prolonged pain history and potential sex differences has not been studied. We used quantitative sensory testing to examine 25 children with migraine between attacks and 28 controls (age 9-15). The assessment included the measurement of heat and mechanical pain thresholds as well as measures of perceptual sensitization in response to repetitive (mechanical) or tonic (thermal) noxious stimulation at both trigeminal and thenar sites. In addition, the mother was either present or absent during the measurements. Heat pain thresholds were not significantly different between the two groups. However, the child migraineurs showed significantly lower mechanical pain thresholds. Children and especially girls with migraine displayed significantly more sensitization to a tonic heat stimulus at the trigeminal site when the mother was present. The migraineurs also showed a trend towards higher sensitization ratings for mechanical stimuli. Overall, heat pain thresholds were significantly higher in the presence of the mother. In the migraine group only, mechanical pain thresholds were significantly higher when the mother was present. To summarize, an enhanced sensitivity to painful stimuli can already be observed in children suffering from migraine for an average duration of 4.4 years. This may be the result of sensitization in nociceptive pain pathways caused by frequent pain experiences. Girls with migraine were more prone to such sensitization, which may increase their risk for continuing to suffer from migraine throughout adulthood.     

Fibromyalgia Patients Are Not Only Hypersensitive to Painful Stimuli But Also to Acoustic Stimuli

Fibromyalgia is a chronic widespread pain syndrome associated with hypersensitivity to nociceptive stimuli. This increased sensitivity of FM patients has been associated with central sensitization of dorsal horn neurons. Increasing evidence, however, suggests that the mechanisms of FM hypersensitivity not only affect pain but include light, smell, and sound. We hypothesized that supraspinal augmentation of sensory input including sound represent a hallmark of FM. We tested 23 FM patients and 28 healthy controls (HC) for sensory augmentation of nociceptive and non-nociceptive sensations: For assessment of nociceptive augmentation we used sensitivity adjusted mechanical and heat ramp & hold stimuli and for assessment of sound augmentation, we applied wideband noise stimuli using a random-staircase design. Quantitative sensory testing demonstrated increased heat and mechanical pain sensitivity in FM participants (P < .001). The sound pressures needed to report mild, moderate, and intense sound levels were significantly lower in FM compared to HC (P < .001), consistent with auditory augmentation.FM patients are not only augmenting noxious sensations but also sound, suggesting that FM augmentation mechanisms are not only operant in the spinal cord but also in the brain. Whether the central nervous system mechanisms for auditory and nociceptive augmentation are similar, needs to be determined in future studies.PerspectiveThis study presents QST evidence that the hypersensitivity of FM patients is not limited to painful stimuli but also to innocuous stimuli like sound. Our results suggest that abnormal brain mechanisms may be responsible for the increased sensitivity of FM patients.     

Laser heat stimulation of tiny skin areas adds valuable information to quantitative sensory testing in postherpetic neuralgia

Patients suffering from postherpetic neuralgia often complain about hypo- or hypersensation in the affected dermatome. The loss of thermal sensitivity has been demonstrated by quantitative sensory testing as being associated with small-fiber (Aδ- and C-fiber) deafferentation. We aimed to compare laser stimulation (radiant heat) to thermode stimulation (contact heat) with regard to their sensitivity and specificity to detect thermal sensory deficits related to small-fiber dysfunction in postherpetic neuralgia. We contrasted detection rate of laser stimuli with 5 thermal parameters (thresholds of cold/warm detection, cold/heat pain, and sensory limen) of quantitative sensory testing. Sixteen patients diagnosed with unilateral postherpetic neuralgia and 16 age- and gender-matched healthy control subjects were tested. Quantitative sensory testing and laser stimulation of tiny skin areas were performed in the neuralgia-affected skin and in the contralateral homologue of the neuralgia-free body side. Across the 5 thermal parameters of thermode stimulation, only one parameter (warm detection threshold) revealed sensory abnormalities (thermal hypoesthesia to warm stimuli) in the neuralgia-affected skin area of patients but not in the contralateral area, as compared to the control group. In contrast, patients perceived significantly less laser stimuli both in the affected skin and in the contralateral skin compared to controls. Overall, laser stimulation proved more sensitive and specific in detecting thermal sensory abnormalities in the neuralgia-affected skin, as well as in the control skin, than any single thermal parameter of thermode stimulation. Thus, laser stimulation of tiny skin areas might be a useful diagnostic tool for small-fiber dysfunction.     

Effect of subthalamic deep brain stimulation on pain in Parkinson’s disease

Painful sensations are common in Parkinson’s disease. In many patients, such sensations correspond to neuropathic pain and could be related to central alterations of pain processing. Subthalamic nuclei deep brain stimulation improves motor function in Parkinson’s disease. Several structures of the basal ganglia are involved in nociceptive function, and deep brain stimulation could thus also modify pain perception in Parkinson’s disease. To test this hypothesis, we compared subjective heat pain thresholds, in deep brain stimulation OFF and ON conditions in 2 groups of Parkinson’s disease patients with or without neuropathic pain. We also compared pain-induced cerebral activations during experimental nociceptive stimulations using H₂¹⁵O positron emission tomography in both deep brain stimulation OFF and ON conditions. Correlation analyses were performed between clinical and neuroimaging results. Deep brain stimulation significantly increased subjective heat pain threshold (from 40.3 ± 4.2 to 41.6 ± 4.3, P = .03) and reduced pain-induced cerebral activity in the somatosensory cortex (BA 40) in patients with pain, whereas it had no effect in pain-free patients. There was a significant negative correlation in the deep brain stimulation OFF condition between pain threshold and pain-induced activity in the insula of patients who were pain free but not in those who had pain. There was a significant positive correlation between deep brain stimulation-induced changes in pain threshold and in pain-induced cerebral activations in the primary somatosensory cortex and insula of painful patients only. These results suggest that subthalamic nuclei deep brain stimulation raised pain thresholds in Parkinson’s disease patients with pain and restored better functioning of the lateral discriminative pain system.     

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.     

Psychophysical and cerebral responses to heat stimulation in patients with central pain, painless central sensory loss, and in healthy persons

Patients with central pain (CP) typically have chronic pain within an area of reduced pain and temperature sensation, suggesting an impairment of endogenous pain modulation mechanisms. We tested the hypothesis that some brain structures normally activated by cutaneous heat stimulation would be hyperresponsive among patients with CP but not among patients with a central nervous system lesion causing a loss of heat or nociceptive sensation with no pain (NP). We used H₂¹⁵O positron emission tomography to measure, in 15 healthy control participants, 10 NP patients, and 10 CP patients, increases in regional cerebral blood flow among volumes of interest (VOI) from the resting (no stimulus) condition during bilateral contact heat stimulation at heat detection, heat pain threshold, and heat pain tolerance levels. Both patient groups had a reduced perception of heat intensity and unpleasantness on the clinically affected side and a bilateral impairment of heat detection. Compared with the HC group, both NP and CP patients had more hyperactive and hypoactive VOI in the resting state and more hyperresponsive and hyporesponsive VOI during heat stimulation. Compared with NP patients, CP patients had more hyperresponsive VOI in the intralaminar thalamus and sensory-motor cortex during heat stimulation. Our results show that focal CNS lesions produce bilateral sensory deficits and widespread changes in the nociceptive excitability of the brain. The increased nociceptive excitability within the intralaminar thalamus and sensory-motor cortex of our sample of CP patients suggests an underlying pathophysiology for the pain in some central pain syndromes.