Conditioned pain modulation in drug-naïve patients with de novo Parkinson's disease.

BACKGROUND: Pain is highly prevalent in patients with Parkinson's disease (PD), but underlying pathophysiological mechanisms are largely unclear. In many chronic pain syndromes deficits in endogenous pain inhibition have been detected that can be assessed using conditioned pain modulation paradigms. Previous studies employing this approach in medicated PD patients did not find abnormal pain inhibition. However, these results might have been confounded by residual dopaminergic medication. METHODS: An established conditioned pain modulation paradigm was used in 17 drug-naïve de novo PD patients and 17 healthy age and gender-matched controls. We tested i) whether conditioned pain modulation responses differed between the patient and control group and ii) whether pain inhibition differed between PD subtypes. RESULTS: PD patients and healthy controls did not differ in their conditioned pain modulation responses. Furthermore, there were no significant differences in CPM responses depending on the PD subtype. However, at a descriptive level, tremor-dominant patients showed a tendency for better descending pain inhibition compared to akinetic-rigid and mixed type patients. CONCLUSIONS: In this first study investigating conditioned pain modulation in de novo PD patients, we found no additional impairment in descending pain modulation besides the known age-related decline. Our findings indicate that mechanisms other than an impaired descending inhibition contribute to high pain prevalence rates in PD and suggest that mechanisms underlying pain may differ between PD subtypes.

Quantitative Sensory Testing (QST) in Drug-Naïve Patients with Parkinson's Disease.

BACKGROUND: Pain is highly prevalent in patients with Parkinson's disease (PD), but underlying pathophysiological mechanisms are largely unclear. Alterations in somatosensory processing might contribute to sensory abnormalities in PD. OBJECTIVE: This study investigated sensory processing in PD patients. METHODS: We used the standardized "Quantitative Sensory Testing" (QST) protocol (German Research Network on Neuropathic Pain) to investigate 13 somatosensory parameters in 19 PD patients naïve to dopaminergic medication and 19 healthy controls matched for age, gender, and handedness. We tested for differences in sensory parameters between i) drug-naïve PD patients and healthy controls, ii) patients' more and less affected body side, and iii) for an association of somatosensory parameters with disease-specific factors. RESULTS: We did not observe any significant group differences in somatosensory parameters between PD patients and healthy subjects. In PD patients, QST mean z-scores did not differ between the predominantly and the less affected body side, PD patients with and without PD-specific chronic pain or between different PD subtypes. Age, but not PD disease severity, was associated with a greater loss of function in thermal and mechanical detection thresholds. CONCLUSIONS: Somatosensory processing, as assessed with the well-established QST protocol, was normal in drug-naïve PD patients. Thus, somatosensory abnormalities previously reported in medicated PD patients might rather be a result of dopaminergic medication, or may occur later in the course of the disease or with increasing age.

Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

Pain in Parkinson disease: a cross-sectional survey of its prevalence, specifics, and therapy.

We aimed to evaluate prevalence, phenotype, and therapeutic realities of pain in patients with Parkinson disease (PD). Therefore, we assessed 181 outpatients with PD using a cross-sectional approach applying the German Pain Questionaire (DSF), the PainDetect, and a self-developed Parkinson Disease Pain Questionaire (UPDPQ) covering detailed therapeutic aspects. Furthermore, we investigated the association between pain and PD-disease characteristics, quality of life (PDQ-39), depression, and anxiety (HADS-D, HADS-A). Overall, prevalence of pain was high (95.4%); 91.1% suffered from chronic pain, but in only 22.3% of them, pain disorder was diagnosed. Pain impaired everyday-life moderately to very severely in 48.4% of patients and was the most distressing symptom in 10.2% of all patients. Pain was localized mainly in the back (71.4%) or joints (52.4%), frequently occurred as pain attacks (79%) but appeared with neuropathic character in only 15.3% of patients. Most patients (74.2%) received some kind of pain treatment, mainly provided by orthopedists (62.0%) or general practitioners (50.0%). Physiotherapy (61.3%), pain killers (54.4%), or massage (35.5%) were the most frequent therapeutic measures. Rehabilitative therapy (96.3%) and physiotherapy (89.5%) were rated as most effective, but with vastly temporary effects. 53.3% of patients attributed PD as the main cause for their pain, but only 33.6% found relief from anti-parkinsonian drugs. High levels of pain were associated with higher scores of depression and anxiety, and lower quality of life. Results suggest that pain in PD is frequent, complex, and quality-of-life-impairing but under-diagnosed and unsystematically treated and indicate need to systematically investigate pathophysiology-based treatment strategies.

Quantitative Sensory Testing in adults with Autism Spectrum Disorders.

Altered sensory perception has been found in patients with autism spectrum disorders (ASD) and might be related to aberrant sensory perception thresholds. We used the well-established, standardized Quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain to investigate 13 somatosensory parameters including thermal and tactile detection and pain thresholds in 13 ASD adults and 13 matched healthy controls with normal IQ values. There were no group differences between somatosensory detection and pain thresholds. Two ASD patients showed paradoxical heat sensations and another two ASD subjects presented dynamic mechanical allodynia; somatosensory features that were absent in controls. These findings suggest that central mechanisms during complex stimulus integration rather than peripheral dysfunctions probably determine somatosensory alterations in ASD.

Quantitative Sensory Testing in adults with Tourette syndrome.

INTRODUCTION: Abnormal sensory perceptions, for instance hypersensitivity to certain external stimuli or premonitory urges preceding tics, are core features in Gilles de la Tourette syndrome (GTS). Aberrant awareness of externally applied stimuli in terms of altered sensory perception thresholds might contribute to these sensory phenomena in GTS. METHODS: We used the well-established and standardized "Quantitative Sensory Testing" (QST) battery (German Research Network on Neuropathic Pain) to investigate 13 sensory parameters including thermal, mechanical/tactile and pain thresholds in 14 GTS patients without clinically significant comorbidities and 14 healthy controls matched for age and gender. RESULTS: There were no relevant group differences in any of the 13 QST parameters and no specific QST pattern in GTS patients. There was no correlation between QST parameters and "Premonitory Urge for Tics scale" (PUTS) scores. CONCLUSION: Our data show that the perceptual threshold detection of externally applied sensory stimuli is normal in adults with GTS. This indicates that other perceptual mechanisms, such as abnormal central sensorimotor processing and/or aberrant interoceptive awareness might underlie the clinically significant sensory abnormalities in GTS.

Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients.

BACKGROUND: Pain is highly prevalent in patients with Parkinson's disease (PD), but little is known about the underlying pathophysiological mechanisms. The susceptibility to pain is known to depend on ascending and descending pathways. Because parts of the descending pain inhibitory system involve dopaminergic pathways, dysregulations in dopaminergic transmission might contribute to altered pain processing in PD. Deficits in endogenous pain inhibition can be assessed using conditioned pain modulation (CPM) paradigms. METHODS: Applying such a paradigm, we investigated i) whether CPM responses differ between PD patients and healthy controls, ii) whether they are influenced by dopaminergic medication and iii) whether there are effects of disease-specific factors. 25 patients with idiopathic PD and 30 healthy age- and gender-matched controls underwent an established CPM paradigm combining heat pain test stimuli at the forearm and the cold pressor task on the contralateral foot as the conditioning stimulus. PD patients were tested under dopaminergic medication and after at least 12 hours of medication withdrawal. RESULTS: No significant differences between CPM responses of PD patients and healthy controls or between PD patients "on" and "off" medication were found. These findings suggest (i) that CPM is insensitive to dopaminergic modulations and (ii) that PD is not related to general deficits in descending pain inhibition beyond the known age-related decline. However, at a trend level, we found differences between PD subtypes (akinetic-rigid, tremor-dominant, mixed) with the strongest impairment of pain inhibition in the akinetic-rigid subtype. CONCLUSIONS: There were no significant differences between CPM responses of patients compared to healthy controls or between patients "on" and "off" medication. Differences between PD subtypes at a trend level point towards different pathophysiological mechanisms underlying the three PD subtypes which warrant further investigation and potentially differential therapeutic strategies in the future.

Age-dependent decline of endogenous pain control: exploring the effect of expectation and depression.

Although chronic pain affects all age ranges, it is particularly common in the elderly. One potential explanation for the high prevalence of chronic pain in the older population is impaired functioning of the descending pain inhibitory system which can be studied in humans using conditioned pain modulation (CPM) paradigms. In this study we investigated (i) the influence of age on CPM and (ii) the role of expectations, depression and gender as potential modulating variables of an age-related change in CPM. 64 healthy volunteers of three different age groups (young = 20-40 years, middle-aged = 41-60 years, old = 61-80 years) were studied using a classical CPM paradigm that combined moderate heat pain stimuli to the right forearm as test stimuli (TS) and immersion of the contralateral foot into ice water as the conditioning stimulus (CS). The CPM response showed an age-dependent decline with strong CPM responses in young adults but no significant CPM responses in middle-aged and older adults. These age-related changes in CPM responses could not be explained by expectations of pain relief or depression. Furthermore, changes in CPM responses did not differ between men and women. Our results strongly support the notion of a genuine deterioration of descending pain inhibitory mechanisms with age.