Microstructural plasticity in nociceptive pathways after spinal cord injury

Abstract

ObjectiveTo track the interplay between (micro-) structural changes along the trajectories of nociceptive pathways and its relation to the presence and intensity of neuropathic pain (NP) after spinal cord injury (SCI).MethodsA quantitative neuroimaging approach employing a multiparametric mapping protocol was used, providing indirect measures of myelination (via contrasts such as magnetisation transfer (MT) saturation, longitudinal relaxation (R1)) and iron content (via effective transverse relaxation rate (R2*)) was used to track microstructural changes within nociceptive pathways. In order to characterise concurrent changes along the entire neuroaxis, a combined brain and spinal cord template embedded in the statistical parametric mapping framework was used. Multivariate source-based morphometry was performed to identify naturally grouped patterns of structural variation between individuals with and without NP after SCI.ResultsIn individuals with NP, lower R1 and MT values are evident in the primary motor cortex and dorsolateral prefrontal cortex, while increases in R2* are evident in the cervical cord, periaqueductal grey (PAG), thalamus and anterior cingulate cortex when compared with pain-free individuals. Lower R1 values in the PAG and greater R2* values in the cervical cord are associated with NP intensity.ConclusionsThe degree of microstructural changes across ascending and descending nociceptive pathways is critically implicated in the maintenance of NP. Tracking maladaptive plasticity unravels the intimate relationships between neurodegenerative and compensatory processes in NP states and may facilitate patient monitoring during therapeutic trials related to pain and neuroregeneration.

Brain morphology changes after spinal cord injury: A voxel-based meta-analysis

“…Our study demonstrated gray matter atrophy in the bilateral thalamus, which was in accordance with previous VBM studies and meta-analyses ( 23 , 34 – 36 ). Although neurons in the brain are not disrupted directly following SCI, the afferent motor pathway and efferent sensory pathway undergo degenerative processes ( 37 , 38 ).…”

Resting state functional connectivity differentiation of neuropathic and nociceptive pain in individuals with chronic spinal cord injury

“…The putamen, a part of the striatum and basal ganglia, is involved with production of movement, reward, and multisensory integration of noxious and non-noxious stimuli, with previously demonstrated pain-related activation hypothesized to be involved in motor responses for withdrawal from painful stimuli or inhibition of painful movement ( Bingel et al, 2002 , Borsook et al, 2010 , Chudler and Dong, 1995 ). Alterations in R2* signal, reflective of iron content, in the parahippocampal gyrus and basal ganglia were previously identified in individuals with SCI with neuropathic pain ( Kyathanahally et al, 2021 ), which demonstrates overlap with our identified alterations in the BOLD signal between the parahippocampal gyrus and putamen. A previously identified negative correlation between neuropathic pain severity in individuals with SCI and mean diffusivity of the amygdala suggest microstructural changes could contribute to our findings of altered amygdala connectivity ( Gustin et al, 2014 ).…”

“… Lee et al, 2022 , Min et al, 2015 , Seixas et al, 2016 , Sprenger et al, 2015 ), putamen ( Iwabuchi et al, 2023 ; B. Lee et al, 2022 , Min et al, 2015 , Ruscheweyh et al, 2018 , Sprenger et al, 2015 , Zhang et al, 2014 ), and the periaqueductal gray matter ( Kyathanahally et al, 2021 , Li et al, 2020a , Linnman et al, 2012 , Sprenger et al, 2015 ) ( Supplemental Fig. 1 ).…”

“…The majority of existing pain literature in PwSCI has focused on structural differences with reported alterations of gray matter volume of the primary somatosensory and motor cortices ( Jutzeler et al, 2016 , Mole et al, 2014 ), anterior cingulate cortex ( Jutzeler et al, 2016 ), thalamus ( Jutzeler et al, 2016 ) and insula ( Yoon et al, 2013 ) in PwSCI with neuropathic pain compared to those without pain or healthy individuals. Alterations in mean diffusivity of the thalamus, amygdala, and insula ( Gustin et al, 2010 ), as well as biochemical differences in the thalamus ( Gustin et al, 2014 , Pattany et al, 2002 , Widerström-Noga et al, 2015 ), anterior cingulate cortex ( Widerström-Noga et al, 2013 ), and periaqueductal gray matter ( Kyathanahally et al, 2021 ) have also been identified in PwSCI with neuropathic pain compared to those without pain or healthy individuals. Additional regions with established roles in pain processing and reported structural or functional differences in PwSCI compared to healthy individuals include the posterior cingulate cortex ( Cermik et al, 2006 ), basal ganglia ( Min et al, 2015 ), and hippocampus and parahippocampal gyri (Q.…”

Spinal cord pathology revealed by MRI in traumatic spinal cord injury

“…Lower MT values within the dorsal columns and spinothalamic tracts are also related to lower light touch and pin-prick scores in chronic SCI, respectively, highlighting the association between remote tract demyelination and specific sensory impairments [44 ▪ ]. Additionally, in terms of microstructural measures revealed by qMRI, higher iron-sensitive R2 ∗ values can also be detected along nociceptive pathways in the cervical cord of chronic SCI patients with NP; its magnitude being associated with pain intensity [45].…”