Central sensitization-related changes of effective and functional connectivity in the rat inflammatory trigeminal pain model

Spisák, Tamás; Pozsgay, Zsófia; Aranyi, Csaba; Dávid, Szabolcs; Kocsis, Pál; Nyitrai, Gabriella; Gajári, Dávid; Emri, Miklós; Czurkó, András; Kincses, Zsigmond Tamás

doi:10.1016/j.neuroscience.2016.12.018

Cited by 23 publications

(41 citation statements)

References 72 publications

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“…While only a few papers have previously highlighted the relationship between resting-state activity and acute pain [22][23][24][25][26]46,47 , several studies have focussed on pain anticipation 12,15-17 i.e. on a pain-free state directly preceding a painful stimulus.…”

Section: Discussionmentioning

confidence: 99%

Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Spisák¹,

Kincses

Schlitt³

et al. 2020

Nat Commun

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Individual differences in pain perception are of interest in basic and clinical research as altered pain sensitivity is both a characteristic and a risk factor for many pain conditions. It is, however, unclear how individual sensitivity to pain is reflected in the pain-free resting-state brain activity and functional connectivity. Here, we identify and validate a network pattern in the pain-free resting-state functional brain connectome that is predictive of interindividual differences in pain sensitivity. Our predictive network signature allows assessing the individual sensitivity to pain without applying any painful stimulation, as might be valuable in patients where reliable behavioural pain reports cannot be obtained. Additionally, as a direct, non-invasive readout of the supraspinal neural contribution to pain sensitivity, it may have implications for translational research and the development and assessment of analgesic treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Spisák¹,

Kincses

Schlitt³

et al. 2020

Nat Commun

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“…To obtain maximally translatable results, we followed the conventions set for human MRI analysis, similar to our previous works 23,55 . Small-animal imaging-specific features of the applied image processing pipeline are described in detail.…”

Section: Imaging Data Analysismentioning

confidence: 99%

“…To achieve spatial correspondence for the group analysis, all images were spatially standardized using FSL FLIRT 60 , which utilized a 6-parameter rigid-body transformation. The high-resolution structural image was fitted to an in-house developed standard template 23 (average of 200 nonlinearly fitted structural images) by an affine transformation (FLIRT) and a nonlinear deformation field estimated by FNIRT 61 . In the latter coregistration procedure, a 10 x 10 x 10 mm 3 warping field (in upscaled space) was estimated with three iterations using a relatively conservative lambda parameter set of 60, 40 and 20.…”

Section: Preprocessingmentioning

confidence: 99%

Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism

Spisák

Román

Papp

et al. 2018

Preprint

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While cerebellar alterations may play a crucial role in the development of core autism spectrum disorder (ASD) symptoms, their pathophysiology on the function of cerebrocerebellar circuit loops is largely unknown. We combined multimodal MRI (9.4 T) brain assessment of the prenatal rat valproate (VPA) model and correlated immunohistological analysis of the cerebellar Purkinje cell number to address this question.We hypothesized that a suitable functional MRI (fMRI) paradigm might show some altered activity related to disrupted cerebrocerebellar information processing. Two doses of maternal VPA (400 and 600 mg/kg, s.c.) were used, and while the higher VPA dose induced a global decrease in whole brain volume, the lower dose induced a focal gray matter density decrease in the cerebellum and brainstem. Increased cortical BOLD responses to whisker stimulation were detected in both VPA groups, but it was more pronounced and extended to cerebellar regions in the 400 mg/kg VPA group. Immunohistological analysis revealed a decreased number of Purkinje cells in both VPA groups. In a detailed analysis, we revealed that the Purkinje cell number interacts with the cerebral BOLD response distinctively in the two VPA groups that highlights atypical function of the cerebrocerebellar circuit loops with potential translational value as an ASD biomarker.

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“…As a whole, these conditions concur to generate stereotyped network configurations, which seemingly appear as anatomo-functional counterparts of the continuous percept of pain, a picture recoverable from all the examined CP models. The model is theoretically sustained by the fact that persistent acute pain elicits massive hyperactivation of thalamocortical neurons strongly modifying the synaptic loads (Vierck et al 2013;Mansour et al 2014), which in turn dramatically alter the functional organization of the involved neuronal networks (Spisák et al 2017;Gustin et al 2012). In this dramatic context, actual conventional CP therapies do not appear adapt to relocate or repair within original limits the disordered network connectivity.…”

Section: Introductionmentioning

confidence: 99%

Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams

Zippo

Bertoli

Riccardi

et al. 2019

Preprint

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Chronic pain (CP) is a condition characterized by a wide spectrum of clinical signs and symptoms, missing a sound modelling at the neuronal network scale. Recently, we presented a general theory showing common electrophysiological traits in different CP rat models, i.e. a collapse of relevant functional connectivity network properties, such as modularity, in the somatosensory thalamo-cortical (TC) network. In this work, we preliminary investigated by an in silico accurate simulator of the six-layer mammalian cortical networks that evidenced the crucial collapse of network modularity in CP simulated conditions and the consequent reduction of network adaptive processes. On this track, in studies on CP experimental animals affected by sciatic nerve multiple ligature (Bennett-Xie model), by synchrotron-generated X-ray microbeam (MB) irradiations (7 parallel beams, 100um width), we targeted in vivo the CP involved hindlimb somatosensory projection cortex that, because of the doses radiation (360 Gy, peak at each beam), non-invasively produced fast and precise tissue destruction along the 7 beam projections. These parcellated the cortical tissue and restored the cortical network statistics related to modularity and information processing efficiency as evidenced from post irradiation in vivo electrophysiological recordings. In addition, by MB treatment there was an ensuing removal of behavioral signs of allodynia and hyperalgesia accompanied by recovered normal gait schemes yet preserving the normal sensory thresholds of the experimental rats up to three months after the MB irradiation. Finally, novel and unprecedented therapeutic appraisals for CP are devised. Significance StatementChronic pain (CP) is an excruciating condition with severe effects on patients' life. Apart from many clinical and experimental studies no current theory on CP is generally accepted. Recently, we proposed a general theory of CP in experimental animals as characterized by strong alteration of the connections among neurons in different brain regions. We show here on in silico simulations that specific connectivity changes in the somatosensory cortex recover the lost functional integrity. Concurrently, in experimental animals, we re-modulated, in vivo, some anatomical connections of the somatosensory cortex by extremely thin synchrotron generated X-ray microbeam irradiations. The resulting behavioral and electrophysiological signs of CP disappeared yet maintaining normal sensory responses. No adverse or pathological effects on blank animals were observable.The results report a multianalytic picture of the effects of high-dose sevenfold X-ray microbeams (MBs) irradiation through the intact skull on the somatosensory cortex of experimental rats in vivo anesthetized with a model of neuropathic Chronic Pain (CP, Figure 1A-F) and control (CR). Early computational inspectionsPreliminary, in silico exploratory analyses offered the possibility to evaluate the effects of guided connectivity interventions on functional and topological substrates of the c...

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Central sensitization-related changes of effective and functional connectivity in the rat inflammatory trigeminal pain model

Cited by 23 publications

References 72 publications

Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Pain-free resting-state functional brain connectivity predicts individual pain sensitivity

Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism

Removal of behavioural and electrophysiological signs of chronic pain byin vivomicrosections of rat somatosensory cortex with parallel X-ray microbeams

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