Journal: Current Research in Neurobiology

Article Title: Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats

doi: 10.1016/j.crneur.2024.100142

Figure Lengend Snippet: Study design and analysis strategy. a Determination of mechanical paw withdrawal threshold was performed prior to (baseline), 24 h after pain model induction (plantar incision (INC), adjuvant/pathogen-induced inflammation induced by plantar injection of Complete Freund's Adjuvants (CFA)), or, as control, brief anesthesia (Isoflurane) only (CTR) in male Sprague-Dawley rats (N = 42). fMRI measurements were performed using two different stimulation modalities (electrical (ES) and mechanical (MS)) with low (1 mA/50g) and high (5 mA/95g) intensity, respectively. b Activated voxels, derived from standard general linear model (GLM) analysis, were assigned to specific brain structures by registration to a digital 3D rat brain atlas. The average time courses of activated voxels per brain structure were extracted, and after regression of their global mean, the residuals were subjected to pair-wise cross-correlation of all activated brain structures. The resulting symmetric correlation map was binarized to all significantly correlating connections (fdr, q = 0.05: network-size comparison) or the 7% strongest connections (topology comparison) and subsequently translated into networks with brain structures as nodes and their respective connections as edges. Edge weight, i.e. the correlation coefficient (Pearson's r), showed connectivity strength. c Global network characteristics were determined using average networks per group. Statistical analysis of specific connections and nodes was performed using single animal networks. NBS: network-based statistics, ANOVA: analysis of variance, LDA: linear discriminant analysis.

Article Snippet: Electrical stimulations (square wave pulses, DS5, Digitimer, Welwyn Garden City, UK) were applied subcutaneously between the second and fourth digit of the right hind paw with two intensities (first, 1 mA: low; second, 5 mA: high at a frequency of 9 Hz and with 2ms pulse duration).

Techniques: Adjuvant, Injection, Control, Derivative Assay, Comparison

Journal: Current Research in Neurobiology

Article Title: Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats

doi: 10.1016/j.crneur.2024.100142

Figure Lengend Snippet: Activation probability of both pain entities after electrical and mechanical stimulation with low (1 mA/50g) and high (5 mA/95g) intensities. a Voxel-wise activation probability maps overlaid on a representative anatomical T1 weighted slice image. The corresponding average T2∗ weighted EPI slice of all rats is shown on the right. b Brain structure-specific activation probability. Length of spokes scales with the number of animals that showed activation in the respective region, referenced to the total number of animals in that group. c Activation probability overlap (pain entity independent) of activated regions with at least 20% activation probability, encoded by the color of the spokes. d Percentage of activated structures with complete overlap of all pain entities. e Percentage of structures activated explicitly by only one entity. am: amygala, au: auditory cortex, CPu: caudate putamen, hip: hippocampus, hyp: hypothalamus, pir: piriform cortex, PtA: parietal association cortex, rhin: ento- and ectorhinale cortex, RS: retrosplenial cortex, S1: primary somatosensory cortex, S2: secondary somatosensory cortex, thal: thalamus, ZI: zona incerta. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Electrical stimulations (square wave pulses, DS5, Digitimer, Welwyn Garden City, UK) were applied subcutaneously between the second and fourth digit of the right hind paw with two intensities (first, 1 mA: low; second, 5 mA: high at a frequency of 9 Hz and with 2ms pulse duration).

Techniques: Activation Assay

Journal: Current Research in Neurobiology

Article Title: Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats

doi: 10.1016/j.crneur.2024.100142

Figure Lengend Snippet: Networks of stimulus- and pain entity-specifically activated brain structures. a Networks with anatomical node positions. All significant connections (determined by FDR with q = 0.05) are displayed. Node size encodes degree, i.e., number of connections. Node colors represent anatomical groups of brain structures (see ). b and c Network density (proportion of all possible connections) and network size (number of nodes) for electrical ( b ) and mechanical ( c ) stimulation. Only brain structures with an activation probability above 20% were taken into account. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Electrical stimulations (square wave pulses, DS5, Digitimer, Welwyn Garden City, UK) were applied subcutaneously between the second and fourth digit of the right hind paw with two intensities (first, 1 mA: low; second, 5 mA: high at a frequency of 9 Hz and with 2ms pulse duration).

Techniques: Activation Assay

Journal: Current Research in Neurobiology

Article Title: Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats

doi: 10.1016/j.crneur.2024.100142

Figure Lengend Snippet: Impact of stimulus modality and intensity on pain entity. Changes in functional connectivities during a electrical stimulation b mechanical stimulation c high intensity stimulation between ES and MS. Only significant components (NBS, p FWE <0.1) are shown for stimulation intensity ( a, b , top), pain entity at high stimulation intensity ( a, b , bottom), and high-intensity stimulation MS vs ES ( c ). Modulations imply for each connection significant ( t -test, p < 0.05, uncorrected) increase (red lines) or decrease (blue lines) of connectivity strength. Node positions were determined using the force-based Kamada-Kawai algorithm derived from high-intensity ES CTR. Node size encodes the number of significantly modulated connections per node. p FWE : significance of modulated component, permutation corrected (NBS). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Electrical stimulations (square wave pulses, DS5, Digitimer, Welwyn Garden City, UK) were applied subcutaneously between the second and fourth digit of the right hind paw with two intensities (first, 1 mA: low; second, 5 mA: high at a frequency of 9 Hz and with 2ms pulse duration).

Techniques: Functional Assay, Derivative Assay

Journal: Current Research in Neurobiology

Article Title: Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats

doi: 10.1016/j.crneur.2024.100142

Figure Lengend Snippet: Post-hoc tests on ANOVA main effects for factor stimulation modality and factor pain model

Article Snippet: Electrical stimulations (square wave pulses, DS5, Digitimer, Welwyn Garden City, UK) were applied subcutaneously between the second and fourth digit of the right hind paw with two intensities (first, 1 mA: low; second, 5 mA: high at a frequency of 9 Hz and with 2ms pulse duration).

Techniques:

Journal: Current Research in Neurobiology

Article Title: Distinct functional cerebral hypersensitivity networks during incisional and inflammatory pain in rats

doi: 10.1016/j.crneur.2024.100142

Figure Lengend Snippet: Mahalanobis distance between corresponding brain regions in LDA separated groups. Left: low stimulation intensity. Right: high stimulation intensity. Only distances of brain structures are displayed that exceed (in at least one comparison per stimulation intensity) the average distance + standard deviation, which is shown by the horizontal line in each diagram. Brain structures were pooled into anatomical groups, marked by colored bars below the x-axis. a,b Mahalanobis distance between CTR and pain models (INC, CFA) after electrical ( a ) or mechanical ( b ) stimulation. c Mahalanobis distance between ES and MS. We calculated the average distance and standard deviation over all pain entities, resulting in one set of brain structure per stimulation intensity.

Article Snippet: Electrical stimulations (square wave pulses, DS5, Digitimer, Welwyn Garden City, UK) were applied subcutaneously between the second and fourth digit of the right hind paw with two intensities (first, 1 mA: low; second, 5 mA: high at a frequency of 9 Hz and with 2ms pulse duration).

Techniques: Comparison, Standard Deviation