Neuroplasticity of Supraspinal Structures Associated with Pathological Pain

Boadas-Vaello, Pere; Homs, Judit; Reina, Francisco; Carrera, Ana; Verdú, Enrique

doi:10.1002/ar.23587

Cited by 42 publications

(40 citation statements)

References 213 publications

(229 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Along these lines, we demonstrated that CP patients with high ACC glutamate levels had increased pain symptoms and a trend towards decreased quality of life for especially the emotional functioning domain of the quality of life questionnaire. High ACC glutamate levels might indicate neuronal hyperexcitability, which is considered to be important in chronification of neuropathic pain (Boadas-Vaello et al, 2017). A previous pilot study showed that in CP patients responding to treatment with transcranial magnetic stimulation, the decrease in pain was correlated to changes in glutamate and NAA levels in the brain (Fregni et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cingulate glutamate levels associate with pain in chronic pancreatitis patients

Hansen

Muthulingam

Drewes

et al. 2019

NeuroImage: Clinical

View full text Add to dashboard Cite

Aims Emerging evidence show that patients with chronic pancreatitis (CP) and abdominal pain have structural and functional alterations in the central nervous system. The aim was to investigate cerebral metabolic signatures in CP and the associations to various risk factors/clinical characteristics and patient outcomes. Methods Magnetic resonance spectroscopy was used to measure brain metabolites in the anterior cingulate cortex (ACC), insula, prefrontal cortex and the parietal region in patients with CP and healthy controls. Subgroup analyses based on disease characteristics (alcoholic etiology of CP, diabetes and opioid treatment) were performed. Finally, relations to abdominal pain symptoms and quality of life scores were explored. Results Thirty-one patients with CP (mean age 58.5 ± 9.2 years) and 23 healthy controls (54.6 ± 7.8 years) were included. Compared to healthy controls, patients had increased glutamate/creatine (glu/cre) levels in the ACC (1.24 ± 0.17 vs. 1.13 ± 0.21, p = .045) and reduced parietal N -acetylaspartate/creatine (NAA/cre) levels (1.44 ± 0.18 vs. 1.54 ± 0.12, p = .027). Patients with alcoholic etiology of CP had significant lower levels of parietal NAA/cre as compared to patients without alcoholic etiology and healthy controls ( p < .006). Patients with a high level of ACC glu/cre reported more severe abdominal pain than their counterparts with a low level of ACC glu/cre (pain score 4.1 ± 2.7 vs.1.9 ± 2.3, p = .039). Conclusions Cerebral spectroscopy revealed novel and complementary information on central pain mechanisms and alcohol mediated toxic effects in patients with CP. Our data suggest that cingulate glutamate levels associate with the patients clinical pain symptoms, while parietal NAA levels more likely associate with an alcoholic etiology of CP.

show abstract

Section: Discussionmentioning

confidence: 99%

Cingulate glutamate levels associate with pain in chronic pancreatitis patients

Hansen

Muthulingam

Drewes

et al. 2019

NeuroImage: Clinical

View full text Add to dashboard Cite

show abstract

“…It has been suggested that proinflammatory mediators (e.g., cytokines) and activation of microglia and astrocytes could be responsible for the structural, functional, and molecular neuroplasticity changes observed in supraspinal structures, associated with pathological pain [ 123 ]. Bilateral increases in the density of microglia are observed in the infralimbic cortex of rats 7 days post-injury, without any detectable change in the other investigated regions, namely the ACC, prelimbic, and agranular insular cortices [ 124 ].…”

Section: Changes In the Pfc During Acute Painmentioning

confidence: 99%

Role of the Prefrontal Cortex in Pain Processing

2018

View full text Add to dashboard Cite

The prefrontal cortex (PFC) is not only important in executive functions, but also pain processing. The latter is dependent on its connections to other areas of the cerebral neocortex, hippocampus, periaqueductal gray (PAG), thalamus, amygdala, and basal nuclei. Changes in neurotransmitters, gene expression, glial cells, and neuroinflammation occur in the PFC during acute and chronic pain, that result in alterations to its structure, activity, and connectivity. The medial PFC (mPFC) could serve dual, opposing roles in pain: (1) it mediates antinociceptive effects, due to its connections with other cortical areas, and as the main source of cortical afferents to the PAG for modulation of pain. This is a 'loop' where, on one side, a sensory stimulus is transformed into a perceptual signal through high brain processing activity, and perceptual activity is then utilized to control the flow of afferent sensory stimuli at their entrance (dorsal horn) to the CNS. (2) It could induce pain chronification via its corticostriatal projection, possibly depending on the level of dopamine receptor activation (or lack of) in the ventral tegmental area-nucleus accumbens reward pathway. The PFC is involved in biopsychosocial pain management. This includes repetitive transcranial magnetic stimulation, transcranial direct current stimulation, antidepressants, acupuncture, cognitive behavioral therapy, mindfulness, music, exercise, partner support, empathy, meditation, and prayer. Studies demonstrate the role of the PFC during placebo analgesia, and in establishing links between pain and depression, anxiety, and loss of cognition. In particular, losses in PFC grey matter are often reversible after successful treatment of chronic pain.

show abstract

“…Overall, despite the available data regarding neuroplastic changes in supraspinal structures associated with nervous system injury-induced pathological pain (Boadas-Vaello et al, 2017 ), the cellular and molecular processes occurring in these structures as a consequence of PNI are not yet fully understood. Particularly, since distinct subregions of PAG may play different or specific roles in the descending modulation of pain (McMullan and Lumb, 2006 ; Eidson and Murphy, 2013 ), it is of interest to investigate whether dlPAG and vlPAG show different pathophysiological responses after PNI, and whether these responses appear in parallel with RVM glial activation, and to do so in distinct PNI models.…”

Section: Introductionmentioning

confidence: 99%

Activation of Astrocytes and Microglial Cells and CCL2/CCR2 Upregulation in the Dorsolateral and Ventrolateral Nuclei of Periaqueductal Gray and Rostral Ventromedial Medulla Following Different Types of Sciatic Nerve Injury

Dubový

Klusáková

Hradilová-Svíženská

et al. 2018

Front. Cell. Neurosci.

Self Cite

View full text Add to dashboard Cite

Peripheral nerve injuries (PNIs) may result in cellular and molecular changes in supraspinal structures possibly involved in neuropathic pain (NPP) maintenance. Activated glial cells in specific supraspinal subregions may affect the facilitatory role of descending pathways. Sterile chronic compression injury (sCCI) and complete sciatic nerve transection (CSNT) in rats were used as NPP models to study the activation of glial cells in the subregions of periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Molecular markers for activated astrocytes (glial fibrillary acidic protein, GFAP) and microglial cells (OX42) were assessed by quantitative immunohistochemistry and western blotting. The cellular distribution of CCL2/CCR2 was monitored using immunofluorescence. sCCI induced both mechanical and thermal hypersensitivity from day 1 up to 3 weeks post-injury. Unilateral sCCI or CSNT for 3 weeks induced significant activation of astrocytes bilaterally in both dorsolateral (dlPAG) and ventrolateral PAG (vlPAG) compared to naïve or sham-operated rats. More extensive astrocyte activation by CSNT compared to sCCI was induced bilaterally in dlPAG and ipsilaterally in vlPAG. Significantly more extensive activation of astrocytes was also found in RVM after CSNT than sCCI. The CD11b immunopositive region, indicating activated microglial cells, was remarkably larger in dlPAG and vlPAG of both sides from sCCI- and CSNT-operated rats compared to naïve or sham-operated controls. No significant differences in microglial activation were detected in dlPAG or vlPAG after CSNT compared to sCCI. Both nerve injury models induced no significant differences in microglial activation in the RVM. Neurons and activated GFAP+ astrocytes displayed CCL2-immunoreaction, while activated OX42+ microglial cells were CCR2-immunopositive in both PAG and RVM after sCCI and CSNT. Overall, while CSNT induced robust astrogliosis in both PAG and RVM, microglial cell activation was similar in the supraspinal structures in both injury nerve models. Activated astrocytes in PAG and RVM may sustain facilitation of the descending system maintaining NPP, while microglial activation may be associated with a reaction to long-lasting peripheral injury. Microglial activation via CCR2 may be due to neuronal and astrocytal release of CCL2 in PAG and RVM following injury.

show abstract

Neuroplasticity of Supraspinal Structures Associated with Pathological Pain

Cited by 42 publications

References 213 publications

Cingulate glutamate levels associate with pain in chronic pancreatitis patients

Cingulate glutamate levels associate with pain in chronic pancreatitis patients

Role of the Prefrontal Cortex in Pain Processing

Activation of Astrocytes and Microglial Cells and CCL2/CCR2 Upregulation in the Dorsolateral and Ventrolateral Nuclei of Periaqueductal Gray and Rostral Ventromedial Medulla Following Different Types of Sciatic Nerve Injury

Contact Info

Product

Resources

About