Tine Maria Hansen

Slowed EEG rhythmicity in patients with chronic pancreatitis: evidence of abnormal cerebral pain processing?

Background and aim Intractable pain usually dominates the clinical presentation of chronic pancreatitis (CP). Slowing of electroencephalogram (EEG) rhythmicity has been associated with abnormal cortical pain processing in other chronic pain disorders. The aim of this study was to investigate the spectral distribution of EEG rhythmicity in patients with CP. Patients and methods Thirty-one patients with painful CP (mean age 52 years, 19 male) and 15 healthy volunteers (mean age 49, nine male) were included. A multichannel EEG was recorded from 62 surface electrodes. Amplitude strengths of the resting EEG were retrieved based on wavelet frequency analysis and summarized in frequency bands with corresponding topographic mapping. Results Patients with CP had slowed EEG rhythmicity compared with healthy volunteers. This was evident as increased activity in the lower frequency bands &dgr; (1–3.5 Hz) (P=0.05), &thgr; (3.5–7.5 Hz) (P<0.001) and &agr; (7.5–13.5 Hz) (P<0.001). Due to normalization a reciprocal relationship was observed for the high frequency band &bgr; (13.5–32 Hz). In a sub-analysis, &dgr; band activity was modified by diabetes, opioid treatment and alcohol aetiology of CP. However, no effect modification was seen for the &thgr; or &agr; bands. Differences in &thgr; activity were located over centro-frontal brain regions, whereas differences in &dgr;, &agr; and &bgr; band activity were located in frontal regions. Conclusion Slowed EEG rhythmicity was evident in patients with CP. This possibly mirrors abnormal central pain processing and may serve as a clinically useful biomarker of abnormal central pain processing.

Morphological and functional evaluation of chronic pancreatitis with magnetic resonance imaging

Magnetic resonance imaging (MRI) techniques for assessment of morphology and function of the pancreas have been improved dramatically the recent years and MRI is very often used in diagnosing and follow-up of chronic pancreatitis (CP) patients. Standard MRI including fat-suppressed T1-weighted and T2-weighted imaging techniques reveal decreased signal and glandular atrophy of the pancreas in CP. In contrast-enhanced MRI of the pancreas in CP the pancreatic signal is usually reduced and delayed due to decreased perfusion as a result of chronic inflammation and fibrosis. Thus, morphological changes of the ductal system can be assessed by magnetic resonance cholangiopancreatography (MRCP). Furthermore, secretin-stimulated MRCP is a valuable technique to evaluate side branch pathology and the exocrine function of the pancreas and diffusion weighted imaging can be used to quantify both parenchymal fibrotic changes and the exocrine function of the pancreas. These standard and advanced MRI techniques are supplementary techniques to reveal morphological and functional changes of the pancreas in CP. Recently, spectroscopy has been used for assessment of metabolite concentrations in-vivo in different tissues and may have the potential to offer better tissue characterization of the pancreas. Hence, the purpose of the present review is to provide an update on standard and advanced MRI techniques of the pancreas in CP.

Cerebral excitability is abnormal in patients with painful chronic pancreatitis

We investigated whether patients with painful chronic pancreatitis (CP) present abnormalities in the cerebral response to experimental pain stimuli.

Spectral and dynamic electroencephalogram abnormalities are correlated to psychometric test performance in hepatic encephalopathy

Abstract Objective. Alterations of the electroencephalogram (EEG) have been reported in patients with hepatic encephalopathy (HE). However, previous methods have not assessed transient phenomena in the EEG signal (dynamics) and associations to psychometric test performance have in general been poor. The aims were to quantify spectral and dynamic EEG abnormalities in patients with HE and to correlate putative findings to psychometric test performances. Methods. Multichannel EEG (64 electrodes) was recorded in 24 cirrhotic patients with various grades of HE and 26 healthy volunteers. Spectral and dynamic EEG indices were quantified by continues wavelet analysis. In addition, the psychometric hepatic encephalopathy score (PHES), continues reaction time, and biochemical profile were assessed. Results. Compared with healthy volunteers, patients had progressively slowing of the EEG (all p ≤ 0.004) (spectral EEG indices) and increased variability in the alpha [7.5–13.5 Hz] (p = 0.001) and beta bands [13.5–32 Hz] (p = 0.02) (dynamic EEG indices). In addition, anteriorization and dissociation of the basic posterior alpha rhythm, along with dissociation of frontal delta activities [1–3.5 Hz] were seen with worsening of HE. Spectral EEG indices (all frequency bands) as well as dynamic EEG indices (alpha and beta bands) were correlated to PHES scores (all p < 0.05). Conclusion. EEG analysis, based on continues wavelet transform, provides quantifiable information on static as well as dynamic features of the EEG in patients with HE. EEG abnormalities were correlated to psychometric test performance and may provide valuable clinical biomarkers for surveillance, prognostication and treatment of this entity.

Cingulate metabolites during pain and morphine treatment as assessed by magnetic resonance spectroscopy

Background Experimental investigation of cerebral mechanisms underlying pain and analgesia are important in the development of methods for diagnosis and treatment of pain. The aim of the current study was to explore brain metabolites in response to pain and treatment with morphine. Methods Proton magnetic resonance spectroscopy of the anterior cingulate cortex was performed in 20 healthy volunteers (13 males and seven females, aged 24.9±2.6 years) during rest and acute pain before and during treatment with 30 mg of oral morphine or placebo in a randomized, double-blinded, cross-over study design. Pain was evoked by skin stimulation applied to the right upper leg using a contact heat-evoked potential stimulator. Results Data from 12 subjects were valid for analysis. Painful stimulation induced an increase in N-acetylaspartate/creatine compared with rest (F=5.5, P=0.04). During treatment with morphine, painful stimulation induced decreased glutamate/creatine (F=7.3, P=0.02), myo-inositol/creatine (F=8.38, P=0.02), and N-acetylaspartate/creatine (F=13.8, P=0.004) concentrations, whereas an increase in the pain-evoked N-acetylaspartate/creatine concentration (F=6.1, P=0.04) was seen during treatment with placebo. Conclusion This explorative study indicates that neuronal metabolites in the anterior cingulate cortex, such as N-acetylaspartate, glutamate, and myo-inositol, could be related to the physiology of pain and treatment with morphine. This experimental method has the potential to enable the study of brain metabolites involved in pain and its treatment, and may in the future be used to provide further insight into these mechanisms.

The Effect of Oral Morphine on Pain-Related Brain Activation – An Experimental Functional Magnetic Resonance Imaging Study

Knowledge about cerebral mechanisms underlying pain perception and effect of analgesic drugs is important for developing methods for diagnosis and treatment of pain. The aim was to explore altered brain activation before and after morphine treatment using functional magnetic resonance imaging recorded during experimental painful heat stimulation. Functional magnetic resonance imaging data were recorded and analysed in 20 healthy volunteers (13 men and 7 women, 24.9 ± 2.6 years) in a randomized, double‐blind, placebo‐controlled, cross‐over study. Painful stimulations were applied to the right forearm using a contact heat evoked potential stimulator (CHEPS) before and after treatment with 30 mg oral morphine and placebo. CHEPS stimulations before treatment induced activation in the anterior cingulate cortex, secondary somatosensory cortex/insula, thalamus and cerebellum (n = 16, p < 0.05). In response to morphine treatment, the spatial extent of these pain‐specific areas decreased (n = 20). Reduced pain‐induced activation was seen in the right insula, anterior cingulate cortex and inferior parietal cortex after morphine treatment compared to before treatment (n = 16, p < 0.05), and sensory ratings of pain perception were significantly reduced after morphine treatment (p = 0.02). No effect on pain‐induced brain activation was seen after placebo treatment compared to before treatment (n = 12, p > 0.05). In conclusion, heat stimulation activated areas in the ‘pain matrix’ and a clinically relevant dose of orally administered morphine revealed significant changes in brain areas where opioidergic pathways are predominant. The method may be useful to investigate the mechanisms of analgesics.

Central response to painful electrical esophageal stimulation in well-defined patients suffering from functional chest pain.

Functional chest pain (FCP) of presumed esophageal origin is considered a common cause for chest pain in which central nervous system hyperexcitability is thought to play an important role. We aimed to compare cerebral responses with painful esophageal stimuli between FCP patients and healthy subjects (HS).

Functional reorganization of brain networks in patients with painful chronic pancreatitis

The underlying pain mechanisms of chronic pancreatitis (CP) are incompletely understood, but recent research points to involvement of pathological central nervous system processing involving pain‐relevant brain areas. We investigated the organization and connectivity of brain networks involved in nociceptive processing in patients with painful CP.

The effects of analgesics on central processing of tonic pain: A cross-over placebo controlled study

Introduction: Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). Methods: Twenty healthy males were included in this randomized, cross‐over, double‐blinded study. 61‐channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b.i.d) or venlafaxine (37.5 mg extended release b.i.d) at rest and during tonic pain (hand immersed in 2 °C water for 80 s). Subjective pain and unpleasantness scores of tonic pain were recorded. Spectral analysis and sLORETA source localization were done in delta (1–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta1 (12–18 Hz) and beta2 (18–32 Hz) frequency bands. Results: Oxycodone decreased pain and unpleasantness scores (P < 0.05), whereas venlafaxine decreased the pain scores (P < 0.05). None of the treatments changed the spectral indices or brain sources underlying resting EEG. Venlafaxine decreased spectral indices in alpha band of the EEG to tonic pain, whereas oxycodone decreased the spectral indices and brain source activity in delta and theta frequency bands (all P < 0.05). The brain source activity predominantly decreased in the insula and inferior frontal gyrus. Conclusion: The decrease of activity within insula and inferior frontal gyrus is likely involved in pain inhibition due to oxycodone treatment, whereas the decrease in alpha activity is likely involved in pain inhibition due to venlafaxine treatment. HighlightsOxycodone decreased delta and theta spectral indices of EEG to tonic pain.Oxycodone decreased the brain activity underlying delta and theta EEG bands.Venlafaxine decreased alpha spectral indices of EEG to tonic pain.Brain activity underlying lower EEG frequencies is likely important in opioid analgesia.Alpha EEG activity is likely important in SNRI analgesia.

Acute Metabolic Changes Associated With Analgesic Drugs: An MR Spectroscopy Study

Magnetic resonance spectroscopy (MRS) is used to measure brain metabolites. Limited data exist on the analgesic‐induced spectroscopy response. This was an explorative study with the aims to investigate the central effects of two analgesic drugs, an opioid and a selective serotonin and norepinephrine reuptake inhibitor, and to explore the association between metabolite changes and the analgesic effect and side effects.