Abnormal spinal cord pain processing in Huntington's disease. The role of the diffuse noxious inhibitory control

ObjectivesOur study is aimed to evaluate the spinal cord pain processing in Huntington’s disease (HD) by testing both the temporal summation threshold (TST) of the nociceptive withdrawal reflex (NWR) and the functional activity of the diffuse noxious inhibitory control (DNIC) as form of supraspinal control of pain.MethodsWe enrolled 19 HD patients and 17 healthy controls. We measured threshold (Th), Area, TST and related psychophysical pain sensations of the NWR, at baseline and during and after activation of the DNIC by means of cold pressor test (CPT) as heterotopic noxious conditioning stimulation.ResultsIn HD patients we found a significantly higher Th and TST as well as a lower Area when compared to controls. During the CPT, a significant inhibition of reflex and psychophysical pain responses were found in both HD patients and controls when compared to baseline, without differences between the groups in CPT results.ConclusionsOur study demonstrated an abnormal spinal cord pain processing in HD patients. Abnormalities in pain processing are not apparently linked to a dysfunctional DNIC inhibitory projection system in HD patients.SignificanceOur findings support the hypothesis that the striatum could play a role in pain modulation and that its atrophy could affect pain processing without change the DNIC efficiency.     

A study of cortical and brainstem mechanisms of diffuse noxious inhibitory controls in anaesthetised normal and neuropathic rats

Diffuse noxious inhibitory controls (DNIC) are a mechanism of endogenous descending pain modulation and are deficient in a large proportion of chronic pain patients. However, the pathways involved remain only partially determined with several cortical and brainstem structures implicated. This study examined the role of the dorsal reticular nucleus (DRt) and infralimbic (ILC) region of the medial prefrontal cortex in DNIC. In vivo electrophysiology was performed to record from dorsal horn lamina V/VI wide dynamic range neurones with left hind paw receptive fields in anaesthetised sham‐operated and L5/L6 spinal nerve‐ligated (SNL) rats. Evoked neuronal responses were quantified in the presence and absence of a conditioning stimulus (left ear clamp). In sham rats, DNIC were reproducibly recruited by a heterotopically applied conditioning stimulus, an effect that was absent in neuropathic rats. Intra‐DRt naloxone had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. In addition, intra‐DRt naloxone blocked DNIC in sham rats, but had no effect in SNL rats. Intra‐ILC lidocaine had no effect on spinal neuronal responses to dynamic brush, punctate mechanical, evaporative cooling and heat stimuli in sham and SNL rats. However, differential effects were observed in relation to the expression of DNIC; intra‐ILC lidocaine blocked activation of DNIC in sham rats but restored DNIC in SNL rats. These data suggest that the ILC is not directly involved in mediating DNIC but can modulate its activation and that DRt involvement in DNIC requires opioidergic signalling.     

Various bilateral olfactory deficits in male patients with schizophrenia

Olfactory identification deficits in schizophrenia patients are well documented. Less is known about the functioning of other olfactory domains and the possibility of lateralized dysfunctions. Thirty male schizophrenia patients and 30 male healthy controls underwent unirhinal assessment of various olfactory domains: detection threshold (dimethyl disulfide, phenyl ethanol), quality discrimination, and odor ratings (familiarity, pleasantness, edibility, intensity) of pure chemicals (Munich Olfaction Test), as well as familiarity and edibility judgments and identification of everyday odors. Aside from impaired identification, patients showed impaired familiarity and edibility judgments of everyday odors. With regard to odor ratings of pure chemicals, group differences were observed only in pleasantness ratings, with higher ratings in patients. Furthermore, patients had reduced sensitivity with dimethyl disulfide and reduced quality discrimination compared with controls. Further analyses showed that identification deficits were not attributable to reduced sensitivity but may be associated with impairments in quality discrimination. Olfactory dysfunctions were found across both nostrils. Results suggest specific dysfunctions in olfactory processing in schizophrenia patients, including early stages of the odor identification process.     

Cross-sectional Study of Glutamate in the Anterior Cingulate and Hippocampus in Schizophrenia

Background: There has been growing support for dysfunctions of the excitatory glutamatergic system and its implications for the psychophysiology of schizophrenia. However, previous studies reported mixed results regarding glutamate concentrations in schizophrenia with varying deviations across brain regions. Methods: We used an optimized proton magnetic resonance spectroscopy procedure to measure absolute glutamate concentrations in the left hippocampal region and the anterior cingulate cortex (ACC) in 29 medicated patients with schizophrenia and in 29 control participants without mental disorder. Results: The glutamate concentrations were significantly lower in the ACC but higher in the hippocampus of patients compared to controls. ACC and hippocampal glutamate concentrations correlated positively in patients but not in controls. ACC glutamate was weakly associated with Clinical Global Impression score and duration of illness in patients. Conclusion: Glutamate concentrations in schizophrenia deviate from controls and show associations with disease severity. A higher concentration of hippocampal glutamate in schizophrenia compared to controls is shown. The association between ACC and hippocampus glutamate concentrations in patients with schizophrenia suggests an abnormal coupling of excitatory systems compared to controls as predicted by previous glutamate models of schizophrenia.Key words: schizophrenia, glutamate, hippocampus, anterior cingulated, MR spectroscopy, glutamatergic hypothesis of schizophrenia     

Noxious mechanical stimuli increase the release of Met-enkephalin-like material heterosegmentally in the rat spinal cord

Although the physiological functions of the endogenous opioid systems are not yet clearly established, it is widely accepted that they exert an inhibitory control on pain transmission. However, the well-documented hypoalgesic effects of low doses of the opiate antagonist naloxone both in animals and humans do not fit in with this concept. The present investigations, at two different spinal/medullary levels (viz. cervicotrigeminal and lumbar) demonstrate that, in the rat, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from neural segments related to the stimulated area of the body, but does increase its release from other segments. Electrophysiological studies have already demonstrated the existence of such heterosegmental mechanisms, notably 'diffuse noxious inhibitory controls' (DNIC), which are naloxone-reversible and could play an important role in pain perception. The involvement of spinal enkephalins in DNIC would seem to mean that the heterosegmental spinal release of MELM triggered by noxious stimuli participates in pain processes.     

Analgesia to pain stimuli in schizophrenics and its reversal by naltrexone.

Psychophysical pain ratings and somatosensory evoked potentials (EPs) were studied in 17 off-medication patients with schizophrenia and 17 age- and sex-matched normal controls. Five of the 17 schizophrenic patients also participated in a clinical trial of naltrexone. In comparison with normal controls, schizophrenic patients were significantly more insensitive to painful stimulation (based on nonparametric analogues of d'from signal detection analysis) and had significantly smaller somatosensory EPs to painful stimuli. Schizophreniucs treated with naltrexone showed significant increases in EP amplitude at higher stimulus intensities and hyperalgesic effects on pain ratings.     

Neural response to experimental heat pain in stable patients with schizophrenia

Diminished pain sensitivity in schizophrenia has been reported in clinical studies. While the role of antipsychotic medications as a cause of the decrease in pain perception has been questioned, little is known about neural pain processing in treated schizophrenia patients. The aim of this pilot study was to examine the blood oxygen level-dependent (BOLD) changes induced by an experimental pain tolerance (endure) hot stimuli vs. non-painful stimuli in clinically stable patients with schizophrenia and in healthy controls. Twelve patients with schizophrenia, treated with risperidone and considered clinically stable, and 13 gender- and age-matched healthy controls were studied using painful and non-painful thermal stimuli in a periodic block design. BOLD changes were assessed using high field, 3?T functional Magnetic Resonance Imaging (fMRI). Pain tolerance in stable patients was not statistically different than healthy controls. Interestingly, patients showed higher activation in the primary somatosensory cortex (S1) and superior prefrontal cortex, and less activation in the posterior cingulate cortex and brainstem than controls. Our pilot study indicates that pain tolerance is similar in clinically stable patients and controls, although the neural processing of pain is not normalized with antipsychotic treatment.     

Assessment of empathy in first-episode psychosis and meta-analytic comparison with previous studies in schizophrenia

Empathy is a multidimensional construct that relies on affective and cognitive component processes. A few studies have reported impairments of both cognitive and affective empathy components in patients with schizophrenia. It is, however, not known whether these difficulties are already present at psychosis onset. The affective and cognitive components of empathy were thus assessed in 31 patients with first-episode psychosis (FEP) and 31 matched healthy controls using the Interpersonal Reactivity Index (IRI). Our results were then compared to previous studies of empathy in patients with more chronic schizophrenia via a meta-analysis. In addition, we also assessed the relationship between empathy ratings, Mentalizing performance and clinical symptoms. Contrary to what has been reported in people with more chronic schizophrenia, the IRI ratings did not significantly differ between FEP and controls in our study, though a trend was observed for the Personal distress scale. For the Perspective taking scale, our meta-analysis revealed a significantly lower effect size in this study with FEP patients relative to previous schizophrenia studies. In the FEP group, the IRI ratings were not related to positive, negative or general psychopathology symptoms, but a significant relationship emerged between the Liebowitz Social Anxiety Scale and Perspective taking (negative correlation). In addition, a significant positive correlation was observed between the Empathic concern subscale and our theory of mind task. This study supports the idea that the cognitive component of empathy is less affected in patients with first-episode psychosis relative to patients with more chronic schizophrenia, and the impairments reported in previous reports with more chronic populations should be interpreted in light of a possible deterioration of this cognitive skill. The findings also provide some insight into the relationship between empathy and clinical symptoms such as social anxiety.     

Gamma frequency-range abnormalities to auditory stimulation in schizophrenia

BACKGROUND: Basic science studies at the neuronal systems level have indicated that gamma-range (30-50 Hz) neural synchronization may be a key mechanism of information processing in neural networks, reflecting integration of various features of an object. Furthermore, gamma-range synchronization is thought to depend on the glutamatergically mediated interplay between excitatory projection neurons and inhibitory neurons utilizing gamma-aminobutyric acid (GABA), which postmortem studies suggest may be abnormal in schizophrenia. We therefore tested whether auditory neural networks in patients with schizophrenia could support gamma-range synchronization. METHODS: Synchronization of the electroencephalogram (EEG) to different rates (20-40 Hz) of auditory stimulation was recorded from 15 patients with schizophrenia and 15 sex-, age-, and handedness-matched control subjects. The EEG power at each stimulation frequency was compared between groups. The time course of the phase relationship between each stimulus and EEG peak was also evaluated for gamma-range (40 Hz) stimulation. RESULTS: Schizophrenic patients showed reduced EEG power at 40 Hz, but not at lower frequencies of stimulation. In addition, schizophrenic patients showed delayed onset of phase synchronization and delayed desynchronization to the click train. CONCLUSIONS: These data provide new information on selective deficits in early-stage sensory processing in schizophrenia, a failure to support the entrainment of intrinsic gamma-frequency oscillators. The reduced EEG power at 40 Hz in schizophrenic patients may reflect a dysfunction of the recurrent inhibitory drive on auditory neural networks.     

Relative food preference and hedonic judgments in schizophrenia

There is a well-documented disruption of the neural network associated with reward evaluation in schizophrenia. This same system is involved in coding the incentive value of food in healthy individuals, but few studies to date have examined anhedonia and its relation to food hedonicity and preference in schizophrenia. Relative preference and hedonic food ratings were examined in schizophrenia patients and healthy controls. In the relative preference task, subjects viewed photographs of food items and selected the one that they most preferred. Hedonic ratings were obtained by asking subjects how much they liked the food stimulus on a scale of 1–5. There were no overall response time differences between the two groups in the relative preference task, but schizophrenia patients showed subtle differences in their hedonic ratings of foods compared with control subjects. Schizophrenia patients gave more positive hedonic ratings for food than did controls, and the use of fewer positive ratings was associated with increased anhedonia, particularly with loss of sexual interest. These results suggest that while making relative preference judgments may be intact, hedonic values attached to food may be altered in schizophrenia, and they may be related to dysfunction in more basic vegetative systems.