Emotional Instability Relates to Ventral Striatum Activity During Reward Anticipation in Females.

Both non-emotional symptoms, such as inattention, and symptoms of emotional instability (EI) are partially co-varying and normally distributed in the general population. Attention Deficit Hyperactivity Disorder (ADHD), which is associated with both inattention and emotional instability, has been related to lower reward anticipation activation in the ventral striatum. However, it is not known whether non-emotional dysregulation, such as inattention, or EI-or both-are associated with this effect. We hypothesized that altered reward processing relates specifically to EI. To test this, 29 healthy participants were recruited to this functional MRI study (n = 15 females). Reward processing was studied using a modified version of the Monetary Incentive Delay (MID) task. Brown Attention-Deficit Disorder Scales questionnaire was used to assess EI and inattention symptoms on a trait level. We observed less ventral striatal activation during reward anticipation related to the EI trait in females, also when controlling for the inattention trait, but not in the whole sample or males only. Our study suggests the existence of sex differences in the relationship between reward processing and EI/inattention traits.

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.

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.

Preserved Capacity for Placebo Analgesia in the Elderly.

The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance. In this study, we compared the response to thermal painful stimuli and the capacity for endogenous pain modulation between younger and older adults using a well established placebo analgesia paradigm involving expectancy and conditioning components. We recruited 30 younger (age 23-40 years, mean = 27.04, standard error of the mean ± .61) and 24 older adults (60-80 years, mean = 69.3, standard error of the mean ± .89). We observed increased heat pain thresholds and higher pain intensity ratings (in response to physically identical heat stimulation) in the older compared with the younger group. However, the placebo analgesic response was comparable between both age groups of healthy participants. The preserved capacity for placebo analgesia in our sample of older participants highlights the potential to use nonpharmacological analgesic treatment strategies in this age group and to exploit placebo mechanisms as an add-on to existing analgesic (pharmacological) treatment strategies. PERSPECTIVE: In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.

Are Children the Better Placebo Analgesia Responders? An Experimental Approach.

UNLABELLED: There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. PERSPECTIVE: This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children.

Haloperidol blocks dorsal striatum activity but not analgesia in a placebo paradigm.

Although placebo analgesia has been associated with an engagement of the endogenous opioid system there is growing evidence from neuropharmacological studies for an involvement of additional neurotransmitter systems. An increased dopaminergic neurotransmission in the ventral basal ganglia that has been found during placebo analgesia suggests a role for the dopaminergic system (Scott et al., 2007). It is, however, unclear whether striatal dopaminergic activity is causally involved in this type of analgesia. This study aimed at exploring the functional role of the dopaminergic system in placebo analgesia. To this end, we investigated the effect of the dopamine D2/D3 receptor antagonist haloperidol on behavioral and neural measures of placebo analgesia using functional magnetic resonance imaging (fMRI) in healthy volunteers. We found that 2 mg haloperidol p.o. significantly reduced the correlation between dorsal striatum activity and the individual placebo response, but had no significant effect on placebo analgesia at the behavioral or neural level, as indexed by activity in sensory or pain-modulatory brain regions. Our study therefore suggests that dopaminergic neurotransmission might not be causally involved in placebo analgesia but is related to phenomena associated with placebo analgesia such as reward processing and learning.

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.