Role In Chronification Research Articles

Role of TNF-α in the Pathogenesis of Migraine.

Neurogenic neuroinflammation has a wide role in migraine pathogenesis including the transition from episodic migraine to chronic one. The seed molecule of neurogenic neuroinflammation, i.e., the TNF-α proinflammatory molecule, has gathered a lot of attention. This pleiotropic cytokine is a classical component of inflammatory soup, secreted by the microglial cell, and promotes a wide range of inflammatory reactions. In this review, we aimed to provide a culminating and comprehending glimpse into the TNF-α in association with the migraine. A systematic literature survey method with a mixture of keywords was utilized to grasp the different elements that represent the association between TNF-α and migraine. Discussion. Highlighted the probable involvement of the TNF-α with migraine, the complexity of the matter such as activation of NF-KB signaling cascade, autoactivation, sensitization, and increased likelihood of transition cannot be neglected. Being TNF-α as a core node, it becomes the factor for linking diseases such as chronic inflammatory disorders, including COVID-19, and also interaction with other genes to develop severe conditions. To this end, TNF-α plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.

Anterior insular volume decrease is associated with dysfunction of the reward system in patients with chronic pain.

Chronification of pain is associated with both anatomical and functional alterations of the brain. Alteration in regional grey matter volume might potentially be associated with modified activity of specific brain networks. In this cross-sectional, observational study, we sought to identify brain regions with grey matter volume changes in patients with chronic pain and to reveal its significance by analysing alteration in functional connectivity from those regions. We further explored relevance of such alterations with psychometrics of chronic pain. We recruited 23 patients with chronic pain and 17 age-, gender-matched healthy control subjects. After completing multiple psychophysical questionnaires, each subject underwent resting-state functional magnetic resonance imaging and three-dimensional anatomical imaging on a 3 Tesla magnetic resonance imaging scanner. Patients with chronic pain showed significant volume decrease at the right anterior insular cortex (p<0.001) and the left middle cingulate cortex (p<0.001) compared with healthy controls. They also showed decreased connectivity between the right anterior insular cortex and the left nucleus accumbens in negative association with the Pain Catastrophizing Scale (R2 =0.20, p=0.046) and the Beck's Depression Inventory scores (R2 =0.24, p=0.017). Decreased grey matter volumes of those core regions for affective processing of pain might be a common cerebral feature shared by, at least some of, different aetiologies of chronic pain. Dysfunctional network between the anterior insular cortex and the nucleus accumbens might reflect affective and motivational disability involved in chronic pain. Such anatomical and functional profiles could potentially be part of a cerebral signature for chronification of pain. This article illustrates decreased network activity of the reward system in association with insular cortical volume decrease in patients with chronic pain, and its close relationships with affective and cognitive morbidity of pain. Attenuation of brain's reward system involving cortical plastic changes might have a key role in chronification of pain.

Attenuation of cortical activity triggering descending pain inhibition in chronic low back pain patients: a functional magnetic resonance imaging study

A considerable portion of chronic low back pain (cLBP) patients lack anatomical abnormality, resist conventional therapeutic interventions, and their symptoms are often complicated with psychological and social factors. Such patients have been reported to show cerebral abnormalities both in anatomy and function by neuroimaging studies. Here we examined differences in cerebral reactivity to a simulated low back pain stimulus between cLBP patients and healthy controls by functional magnetic resonance imaging (fMRI), and their behavioral correlates from a psychophysical questionnaire. Eleven cLBP patients and 13 healthy subjects (HS) were enrolled in this study. After psychophysical evaluation on-going pain with McGill Pain Questionnaire Short Form (MPQ), they underwent whole-brain fMRI in a 3-Tesla MRI scanner while receiving three blocks of 30-s mechanical pain stimuli at the left low back with a 30-s rest in between, followed by a three-dimensional anatomical imaging. Functional images were analyzed with a multi-subject general linear model for blood oxygenation level-dependent (BOLD) signal changes associated with pain. Individual BOLD signal amplitudes at activated clusters were examined for correlation with psychophysical variables. Two in the cLBP and five data sets in the HS groups were excluded from analysis because of deficient or artifactual data or mismatch in age. The HS group showed LBP-related activation at the right insular cortex, right dorsolateral prefrontal cortex (DLPFC), left anterior cingulate cortex (ACC), and left precuneus; and deactivation in a large area over the parietal and occipital cortices, including the bilateral superior parietal cortex. On the other hand, the cLBP group did not show any significant activation at those cortical areas, but showed similar deactivation at the bilateral superior parietal cortex and part of the premotor area. An HS>cLBP contrast revealed significantly less activity at the ACC and DLPFC in the cLBP group, which was negatively correlated with higher MPQ scores. The cLBP patients showed attenuated reactivity to pain at the ACC and DLPFC, known cortical areas mediating affective component, and top-down modulation, of pain. The present results might be associated with possible dysfunction of the descending pain inhibitory system in patients with chronic low back pain, which might possibly play a role in chronification of pain.

Neuroprogression in Schizophrenia and Psychotic Disorders: The Possible Role of Inflammation.

Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e.g., increased levels of cytokines such as interleukin-6 (IL-6). Moreover, the tryptophan/kynurenine metabolism is regulated via pro- and anti-inflammatory cytokines and is closely related to the glutamatergic neurotransmission. Certain molecules of this metabolism, such as quinolinic acid or 3OH-kynurenine, have neurotoxic effects and seem to play a role in chronification. Studies with immune/anti-inflammatory-based therapeutic approaches show that acuity or chronicity of the inflammation influence the outcome of therapeutic interventions.

A magnetoencephalography study of multi-modal processing of pain anticipation in primary sensory cortices.

Pain anticipation plays a critical role in pain chronification and results in disability due to pain avoidance. It is important to understand how different sensory modalities (auditory, visual or tactile) may influence pain anticipation as different strategies could be applied to mitigate anticipatory phenomena and chronification. In this study, using a countdown paradigm, we evaluated with magnetoencephalography the neural networks associated with pain anticipation elicited by different sensory modalities in normal volunteers. When encountered with well-established cues that signaled pain, visual and somatosensory cortices engaged the pain neuromatrix areas early during the countdown process, whereas the auditory cortex displayed delayed processing. In addition, during pain anticipation, the visual cortex displayed independent processing capabilities after learning the contextual meaning of cues from associative and limbic areas. Interestingly, cross-modal activation was also evident and strong when visual and tactile cues signaled upcoming pain. Dorsolateral prefrontal cortex and mid-cingulate cortex showed significant activity during pain anticipation regardless of modality. Our results show pain anticipation is processed with great time efficiency by a highly specialized and hierarchical network. The highest degree of higher-order processing is modulated by context (pain) rather than content (modality) and rests within the associative limbic regions, corroborating their intrinsic role in chronification.

971 FEAR-AVOIDANCE- AND ENDURANCE-RELATED RESPONSES TO PAIN IN MIGRAINE PATIENTS

Introduction: Research has shown that there are disease relevant psychological factors which have an influence on the onset and course of pain disorders. In the past decade, research in patients with low back pain (LBP) has detected painrelated fear-avoidance and endurance responses (FAR and ER) as risk factors for the development of chronic pain1. In migraine, only FAR are investigated so far2,3. One reason for this could be the high comorbidity with psychiatric diseases as major depression and anxiety disorders in migraine. Although there are first indications that endurance responses could play a role in chronification of migraine4, a systematic research is missing.