Longitudinal alterations of the cisternal segment of trigeminal nerve and brain pain-matrix regions in patients with trigeminal neuralgia before and after treatment

Background Trigeminal neuralgia (TN) is the most common type of chronic neuropathic facial pain, but the etiology and pathophysiological mechanisms after treatment are still not well understood. The purpose of this study was to investigate the longitudinal changes of the cisternal segment of the trigeminal nerve and brain pain-related regions in patients with TN before and after treatment using readout segmentation of long variable echo-train (RESOLVE) diffusion tensor imaging (DTI) and transverse relaxation (T2)-weighted sampling perfection with application-optimized contrast at different flip angle evolutions (T2-SPACE). Methods Twelve patients with TN and four healthy controls were enrolled in this study. All patients underwent assessment of the visual analog scale (VAS), and acquisition of RESOLVE DTI and T2-SPACE images before and at 1, 6, and 12 months after treatments. Regions-of-interest were placed on the bilateral anterior, middle, and posterior parts of the cisternal segment of the trigeminal nerve, the bilateral root entry zone (REZ), bilateral nuclear zone, and the center of pontocerebellar tracts, respectively. Voxel-based morphometry (VBM) analysis was conducted with T2-SPACE images, and gray matter volumes (GMV) were measured from brain pain-matrix regions. Results The results demonstrated that the VAS scores, the axial diffusivity of the middle part of the affected cisternal trigeminal nerve, the fractional anisotropy of the bilateral nuclear zones, and the mean diffusivity of the center of pontocerebellar tract significantly changed over time before and after treatment. The changes of GMV in the pain-matrix regions exhibited similar trends to the VAS before and after treatment. Conclusion We conclude that magnetic resonance imaging with RESOLVE DTI and VBM with T2-SPACE images were helpful in the understanding of the pathophysiological mechanisms in patients with TN before and after treatment.

Functional and structural neuroplastic changes related to sensitization proxies in patients with Osteoarthritis: a systematic review

Objective Several reports in literature have identified sensitization as a possible basis for the enhanced pain reactions associated with Osteoarthritis (OA). The aim of this current systematic review is to summarize functional and structural brain changes associated with surrogate sensitization parameters assessed in patients with OA-related pain. Design Systematic review. Subjects Patients with OA related pain. Methods A literature search was conducted systematically in MEDLINE, CINAHL, EMBASE databases for human studies up to December 2019. Articles were included if they assessed brain imaging and senzitisation parameters (quantitative sensory testing and questionnaires) in adults with OA related pain. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) score. Results Five studies reporting on 138 patients were included in this review. The MINORS scale yielded mean scores of 8.5/16 and 12.3/24, for the cohort and case-control studies respectively. Four low-quality studies suggest a greater pain matrix activation associated with clinical measures of sensitization in patients with OA, while another study underlined the presence of structural changes (reduced gray matter volume) in the cortical areas involved in the nociceptive processing possible also related to sensitization. Conclusion This review shows conflicting evidence for structural and functional neuroplastic brain changes related to sensitization proxies in patients with OA.

Longitudinal Alterations of the Cisternal Segment of Trigeminal Nerve and Brain Pain-matrix Regions in Patients with Trigeminal Neuralgia Before and After Treatment

Background: Trigeminal neuralgia (TN) is the most common type of chronic neuropathic facial pain, but the etiology and pathophysiological mechanisms after treatment are still not well understood. The purpose of this study was to investigate the longitudinal changes of the cisternal segment of the trigeminal nerve and brain pain-related regions in patients with TN before and after treatment using readout segmentation of long variable echo-train (RESOLVE) diffusion tensor imaging (DTI) and transverse relaxation (T2)-weighted sampling perfection with application-optimized contrast at different flip angle evolutions (T2-SPACE). Methods: Twelve patients with TN and four healthy controls were enrolled in this study. All patients underwent assessment of the visual analog scale (VAS), and acquisition of RESOLVE DTI and T2-SPACE images before and at 1, 6, and 12 months after treatments. Regions-of-interest were placed on the bilateral anterior, middle, and posterior parts of the cisternal segment of the trigeminal nerve, the bilateral root entry zone (REZ), bilateral nuclear zone, and the center of pontocerebellar tracts, respectively. Voxel-based morphometry (VBM) analysis was conducted with T2-SPACE images, and gray matter volumes (GMV) were measured from brain pain-matrix regions. Results: The results demonstrated that the axial diffusivity of the middle part of the cisternal trigeminal nerve, the fractional anisotropy of the bilateral nuclear zones, and the mean diffusivity of the center of pontocerebellar tract significantly changed over time before and after treatment. The changes of GMV in the pain-matrix regions exhibited similar trends to the VAS before and after treatment. Conclusion: We conclude that magnetic resonance imaging with RESOLVE DTI and VBM with T2-SPACE images were helpful in the understanding of the pathophysiological mechanisms in patients with TN before and after treatment.

Involvement of Parvalbumin-Positive Neurons in the Development of Hyperalgesia in a Mouse Model of Fibromyalgia

Fibromyalgia (FM) presents as chronic systemic pain, which might be ascribed to central sensitization, in which pain information processing is amplified in the central nervous system. Since patients with FM display elevated gamma oscillations in the pain matrix and parvalbumin (PV)-positive neurons play a critical role in induction of gamma oscillations, we hypothesized that changes in PV-positive neurons are involved in hyperalgesia in fibromyalgia. In the present study, to investigate a role of PV-positive neurons in neuropathic pain, mice received reserpine administration for 3 consecutive days as an animal model of FM (RES group), while control mice received vehicle injections in the same way (VEH group). The mice were subjected to hot-plate and forced swim tests, and immuno-stained PV-positive neurons were counted in the pain matrix. We investigated relationships between PV-positive neuron density in the pain matrix and pain avoidance behaviors. The results indicated that the mice in the RES group showed transient bodyweight loss and longer immobility time in the forced swim test than the mice in the VEH group. In the hot-plate test, the RES group showed shorter response latencies and a larger number of jumps in response to nociceptive thermal stimulus than the VEH group. Histological examination indicated an increase in the density of PV-positive neurons in the primary somatosensory cortex (S1) in the RES group. Furthermore, response latencies to the hot-plate were significantly and negatively correlated with the density of PV-positive neurons in the S1. These results suggest a critical role for PV-positive neurons in the S1 to develop hyperalgesia in FM.

Peripheral arterial stiffness during electrocutaneous stimulation is positively correlated with pain-related brain activity and subjective pain intensity: an fMRI study

Brain activity associated with pain perception has been revealed by numerous PET and fMRI studies over the past few decades. These findings helped to establish the concept of the pain matrix, which is the distributed brain networks that demonstrate pain-specific cortical activities. We previously found that peripheral arterial stiffness $${\beta }_{\text{art}}$$ β art responds to pain intensity, which is estimated from electrocardiography, continuous sphygmomanometer, and photo-plethysmography. However, it remains unclear whether and to what extent $${\beta }_{\text{art}}$$ β art aligns with pain matrix brain activity. In this fMRI study, 22 participants received different intensities of pain stimuli. We identified brain regions in which the blood oxygen level-dependent signal covaried with $${\beta }_{\text{art}}$$ β art using parametric modulation analysis. Among the identified brain regions, the lateral and medial prefrontal cortex and ventral and dorsal anterior cingulate cortex were consistent with the pain matrix. We found moderate correlations between the average activities in these regions and $${\beta }_{\text{art}}$$ β art (r = 0.47, p < 0.001). $${\beta }_{\text{art}}$$ β art was also significantly correlated with self-reported pain intensity (r = 0.44, p < 0.001) and applied pain intensity (r = 0.43, p < 0.001). Our results indicate that $${\beta }_{\text{art}}$$ β art is positively correlated with pain-related brain activity and subjective pain intensity. This study may thus represent a basis for adopting peripheral arterial stiffness as an objective pain evaluation metric.

A fájdalomélmény kialakulásának korszerű megközelítése

According to the basic assumption of pain research, the activity of pain matrix shows an increase in functional neuroimaging studies during nociceptive stimulation whose extent is correlated with the intensity of the stimulus and that of the emerged experience of pain. Research conducted over the past decade has questioned this assumption. In order to understand the controversial findings I have reviewed new results of pain research. In order to get to know more about “hardware”, I reviewed the direct relationships between members of the pain network. With a view to understand the mechanism of the development of pain perception, the “software”, I give a brief description of the functioning of the salient as well as attention and executive control network. To have a better understanding of “hardware”, I examined the behavior of the pain network of patients incapable of feeling pain in aversive situations. In the review I introduced the thought-provoking knowledge of the pain for all experts, regardless of this specialty by presenting the results of pain research.

Some like it, some do not: behavioral responses and central processing of olfactory–trigeminal mixture perception

Exploring the potential of eucalyptol as a masking agent for aversive odors, we found that eucalyptol masks the olfactory but not the trigeminal sensation of ammonia in a previous study. Here, we further investigate the processing of a mixture consisting of eucalyptol and ammonia, two olfactory–trigeminal stimuli. We presented the two pure odors and a mixture thereof to 33 healthy participants. The nostrils were stimulated alternately (monorhinal application). We analyzed the behavioral ratings (intensity and pleasantness) and functional brain images. First, we replicated our previous finding that, within the mixture, the eucalyptol component suppressed the olfactory intensity of the ammonia component. Second, mixture pleasantness was rated differently by participants depending on which component dominated their mixture perception. Approximately half of the volunteers rated the eucalyptol component as more intense and evaluated the mixture as pleasant (pleasant group). The other half rated the ammonia component as more intense and evaluated the mixture as unpleasant (unpleasant group). Third, these individual differences were also found in functional imaging data. Contrasting the mixture either to eucalyptol or to both single odors, neural activation was found in the unpleasant group only. Activation in the anterior insula and SII was interpreted as evidence for an attentional shift towards the potentially threatening mixture component ammonia and for trigeminal enhancement. In addition to insula and SII, further regions of the pain matrix were involved when assessing all participant responses to the mixture. Both a painful sensation and an attentional shift towards the unpleasant mixture component complicates the development of an efficient mask because a pleasant perception is an important requirement for malodor coverage.