Invasive Motor Cortex Stimulation Influences Intracerebral Structures in Patients With Neuropathic Pain: An Activation Likelihood Estimation Meta-Analysis of Imaging Data

Zhang

et al. 2021

IJMS

Neuropathic pain is difficult to cure and is often accompanied by emotional and psychological changes. Exploring the mechanisms underlying neuropathic pain will help to identify a better treatment for this condition. The insular cortex is an important information integration center. Numerous imaging studies have documented increased activity of the insular cortex in the presence of neuropathic pain; however, the specific role of this region remains controversial. Early studies suggested that the insular lobe is mainly involved in the processing of the emotional motivation dimension of pain. However, increasing evidence suggests that the role of the insular cortex is more complex and may even be related to the neural plasticity, cognitive evaluation, and psychosocial aspects of neuropathic pain. These effects contribute not only to the development of neuropathic pain, but also to its comorbidity with neuropsychiatric diseases. In this review, we summarize the changes that occur in the insular cortex in the presence of neuropathic pain and analgesia, as well as the molecular mechanisms that may underlie these conditions. We also discuss potential sex-based differences in these processes. Further exploration of the involvement of the insular lobe will contribute to the development of new pharmacotherapy and psychotherapy treatments for neuropathic pain.

Section: Structural and Functional Changes Occurring In The Insulamentioning

confidence: 99%

Current Understanding of the Involvement of the Insular Cortex in Neuropathic Pain: A Narrative Review

Zhang

et al. 2021

IJMS

“…The median NRS score did not significantly decrease in the sham arm ( 55 ). Currently, the lack of clear guidelines regarding the frequency and stimulation amplitude necessary to achieve sufficient pain reduction currently limits the use of TENS ( 57 , 198 , 199 ). A phase III study would be necessary to prove the effect of Scrambler therapy on pain, reduction in analgesic medication, and QoL in a larger NMOSD cohort ( 57 , 198 , 199 ).…”

Section: Treatment Of Pain In Nmosd and Mogadmentioning

confidence: 99%

Pain in NMOSD and MOGAD: A Systematic Literature Review of Pathophysiology, Symptoms, and Current Treatment Strategies

2020

Neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are autoimmune inflammatory disorders of the central nervous system (CNS). Pain is highly prevalent and debilitating in NMOSD and MOGAD with a severe impact on quality of life, and there is a critical need for further studies to successfully treat and manage pain in these rare disorders. In NMOSD, pain has a prevalence of over 80%, and pain syndromes include neuropathic, nociceptive, and mixed pain, which can emerge in acute relapse or become chronic during the disease course. The impact of pain in MOGAD has only recently received increased attention, with an estimated prevalence of over 70%. These patients typically experience not only severe headache, retrobulbar pain, and/or pain on eye movement in optic neuritis but also neuropathic and nociceptive pain. Given the high relevance of pain in MOGAD and NMOSD, this article provides a systematic review of the current literature pertaining to pain in both disorders, focusing on the etiology of their respective pain syndromes and their pathophysiological background. Acknowledging the challenge and complexity of diagnosing pain, we also provide a mechanism-based classification of NMOSD- and MOGAD-related pain syndromes and summarize current treatment strategies.

Journal of Neurophysiology

“…Thus, the MCC has been proposed to act as a hub between affective processing, pain, cognitive control, and motor planning ( 62 , 63 ). Engagement of the MCC during LFS has relevance for neuropathic pain treatments; motor cortex stimulation for neuropathic pain has been shown to increase cerebral blood flow in regions including the cingulate gyrus ( 64 ), and transcranial magnetic stimulation over medial scalp regions corresponding to the MCC decreases ratings of noxious electrical stimulation ( 65 ). Taken together, decreased MCC responses during LFS at intensities greater than perception may reflect reduced engagement of cingulate nociceptive pathways, which are implicated in neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Intensity-dependent modulation of cortical somatosensory processing during external, low-frequency peripheral nerve stimulation in humans

Hewitt

Newton‐Fenner

Henderson

et al. 2022

External low-frequency peripheral nerve stimulation (LFS) has been proposed as a novel method for neuropathic pain relief. Previous studies have reported that LFS elicits long-term depression-like effects on human pain perception when delivered at noxious intensities, while lower intensities are ineffective. To shed light on cortical regions mediating the effects of LFS, we investigated changes in somatosensory-evoked potentials (SEPs) during four LFS intensities. LFS was applied to the radial nerve (600 pulses, 1 Hz) of twenty-four healthy participants at perception (1×), low (5×), medium (10×) and high intensities (15× detection threshold). SEPs were recorded during LFS, and averaged SEPs in 10 consecutive one-minute epochs of LFS were analysed using source dipole modelling. Changes in resting electroencephalography (EEG) were investigated after each LFS block. Source activity in the midcingulate cortex (MCC) decreased linearly during LFS, with greater attenuation at stronger LFS intensities, and in the ipsilateral operculo-insular cortex during the two lowest LFS stimulus intensities. Increased LFS intensities resulted in greater augmentation of contralateral primary sensorimotor cortex (SI/MI) activity. Stronger LFS intensities were followed by increased alpha (9-11 Hz) band power in SI/MI and decreased theta (3-5 Hz) band power in MCC. Intensity-dependent attenuation of MCC activity with LFS is consistent with a state of long-term depression. Sustained increases in contralateral SI/MI activity suggests that effects of LFS on somatosensory processing may also be dependent on satiation of SI/MI. Further research could clarify if the activation of SI/MI during LFS competes with nociceptive processing in neuropathic pain.