MR-guided Focused Ultrasound Thalamotomy for Chronic Pain.

MR-guided focused ultrasound (FUS) represents a promising alternative for patients with chronic neuropathic who have failed medical management and other treatment options. Early single-center experience with chronic neuropathic pain and trigeminal neuralgia has demonstrated favorable long-term outcomes. Excellent safety profile with low risk of motor and sensory complications and so far anecdotal permanent neurologic deficits make FUS a powerful tool to treat patients who are otherwise hopeless. Neuromodulation may be the most influential factor driving outcomes and studies devised to detect neuroplasticity will be critical to guide such therapies.

Contributions of neuroimaging in central poststroke pain: a review.

BACKGROUND: Central neuropathic poststroke pain (CNPSP) affects up to 12% of patients with stroke in general and up to 18% of patients with sensory deficits. This pain syndrome is often incapacitating and refractory to treatment. Brain computed tomography and magnetic resonance imaging (MRI) are widely used methods in the evaluation of CNPSP. OBJECTIVE: The present study aims to review the role of neuroimaging methods in CNPSP. METHODS: We performed a literature review of the main clinical aspects of CNPSP and the contribution of neuroimaging methods to study its pathophysiology, commonly damaged brain sites, and possible differential diagnoses. Lastly, we briefly mention how neuroimaging can contribute to the non-pharmacological CNPSP treatment. Additionally, we used a series of MRI from our institution to illustrate this review. RESULTS: Imaging has been used to explain CNPSP pathogenesis based on spinothalamic pathway damage and connectome dysfunction. Imaging locations associated with CNPSP include the brainstem (mainly the dorsolateral medulla), thalamus (especially the ventral posterolateral/ventral posteromedial nuclei), cortical areas such as the posterior insula and the parietal operculum, and, more recently, the thalamocortical white matter in the posterior limb of the internal capsule. Imaging also brings the prospect of helping search for new targets for non-pharmacological treatments for CNPSP. Other neuropathic pain causes identified by imaging include syringomyelia, multiple sclerosis, and herniated intervertebral disc. CONCLUSION: Imaging is a valuable tool in the complimentary evaluation of CNPSP patients in clinical and research scenarios.

ANTECEDENTES: A dor neuropática central pós-acidente vascular cerebral (DNPAVC) afeta até 12% dos pacientes com AVC em geral e até 18% dos pacientes com déficits sensoriais. Essa síndrome dolorosa costuma ser incapacitante e refratária ao tratamento. A tomografia computadorizada e a ressonância magnética do cérebro são métodos amplamente utilizados na avaliação da DNPAVC. OBJETIVO: Este estudo tem como objetivo revisar o papel dos métodos de neuroimagem na DNPAVC. MéTODOS: Realizamos uma revisão da literatura sobre os principais aspectos clínicos da DNPAVC e a contribuição dos métodos de neuroimagem para estudar a fisiopatologia da DNPAVC, locais cerebrais comumente lesados na DNPAVC e possíveis diagnósticos diferenciais. Por fim, mencionamos brevemente como a neuroimagem pode contribuir no tratamento não farmacológico da DNPAVC. Além disso, utilizamos uma série de imagens de ressonância magnética da nossa instituição para ilustrar esta revisão. RESULTADOS: Os exames de imagem têm sido usados para explicar a patogênese da DNPAVC com base no dano da via espinotalâmica e na disfunção do conectoma. Os locais de imagem associados à DNPAVC incluem o tronco cerebral (principalmente o bulbo dorsolateral), o tálamo (especialmente os núcleos ventral posterolateral/ventral posteromedial), áreas corticais como a ínsula posterior e o opérculo parietal e, mais recentemente, a substância branca tálamo-cortical no membro posterior da cápsula interna. Os exames de imagem também trazem a perspectiva de auxiliar na busca de novos alvos para tratamentos não farmacológicos para DNPAVC. Outras causas de dor neuropática identificadas por exames de imagem incluem siringomielia, esclerose múltipla e hérnia de disco intervertebral. CONCLUSãO: Os exames de imagem são uma ferramenta valiosa na avaliação complementar de pacientes com DNPAVC em cenários clínicos e de pesquisa.

Acupuncture Modulation of Chronic Neuropathic Pain and Its Association With Brain Functional Properties.

Chronic neuropathic pain has been one of the prominent causes of disability, and acupuncture has shown promise in treatment. The present study aimed to characterize acupuncture modulation of chronic neuropathic pain and explore the related functional brain changes. Sixty chronic sciatica patients were divided into acupuncture- or sham acupuncture groups and received 10 sessions of treatment during 4 weeks. The visual analog scale for leg pain, oswestry disability index (ODI), and resting-state functional magnetic resonance images were assessed at baseline and after treatment. Then, fractional amplitudes of low-frequency fluctuations (fALFF) and support vector regression analyses were performed. Compared with sham acupuncture, acupuncture significantly improved symptoms, including visual analog scale for leg pain and ODI. In addition, acupuncture exhibited increased fALFF of the right superior parietal lobule (SPL) and right postcentral gyrus. Furthermore, the actual 4-week ODI values were positively correlated with the support vector regression-predicted values based on the right SPL fALFF and baseline clinical measurements. These results indicate that the spontaneous neural activity of the right SPL and right postcentral gyrus may be involved in the modulation of acupuncture in chronic neuropathic pain. In addition, the spontaneous neural activity of the right SPL might be used as the predictor of response to acupuncture therapy. PERSPECTIVE: This clinical neuroimaging study elucidated the neural basis of acupuncture in chronic sciatica. Neurological indicators and clinical measurements could be used as potential predictors of acupuncture response. This study combines neuroimaging and artificial intelligence techniques to highlight the potential of acupuncture for the treatment of chronic neuropathic pain. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100044585, http://www.chictr.org.cn.

Recent developments and challenges in positron emission tomography imaging of gliosis in chronic neuropathic pain.

ABSTRACT: Understanding the mechanisms that underpin the transition from acute to chronic pain is critical for the development of more effective and targeted treatments. There is growing interest in the contribution of glial cells to this process, with cross-sectional preclinical studies demonstrating specific changes in these cell types capturing targeted timepoints from the acute phase and the chronic phase. In vivo longitudinal assessment of the development and evolution of these changes in experimental animals and humans has presented a significant challenge. Recent technological advances in preclinical and clinical positron emission tomography, including the development of specific radiotracers for gliosis, offer great promise for the field. These advances now permit tracking of glial changes over time and provide the ability to relate these changes to pain-relevant symptomology, comorbid psychiatric conditions, and treatment outcomes at both a group and an individual level. In this article, we summarize evidence for gliosis in the transition from acute to chronic pain and provide an overview of the specific radiotracers available to measure this process, highlighting their potential, particularly when combined with ex vivo / in vitro techniques, to understand the pathophysiology of chronic neuropathic pain. These complementary investigations can be used to bridge the existing gap in the field concerning the contribution of gliosis to neuropathic pain and identify potential targets for interventions.

Pretreatment Brain White Matter Integrity Associated With Neuropathic Pain Relief and Changes in Temporal Summation of Pain Following Ketamine.

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP. We used a fixel-based analysis of diffusion-weighted imaging data to evaluate WM microstructure (fiber density [FD]) and macrostructure (fiber bundle cross-section) within the DMN and mPFC-PAG pathways in 70 individuals who underwent magnetic resonance imaging and TSP testing; 35 with NP who underwent ketamine treatment and 35 age- and sex-matched pain-free individuals. Individuals with NP were assessed before and 1 month after treatment; those with ≥30% pain relief were considered responders (n = 18), or otherwise as nonresponders (n = 17). We found that WM structure within the DMN and mPFC-PAG pathways did not differentiate responders from nonresponders. However, pretreatment FD in the anterior limb of the internal capsule correlated with pain relief (r=.48). Moreover, pretreatment FD in the DMN (left mPFC-precuneus/posterior cingulate cortex; r=.52) and mPFC-PAG (r=.42) negatively correlated with changes in TSP. This suggests that WM microstructure in the DMN and mPFC-PAG pathway is associated with the degree to which ketamine reduces central sensitization. Thus, fixel metrics of WM structure may hold promise to predict ketamine NP treatment outcomes. PERSPECTIVE: We used advanced fixel-based analyses of MRI diffusion-weighted imaging data to identify pretreatment WM microstructure associated with ketamine outcomes, including analgesia and markers of attenuated central sensitization. Exploring associations between brain structure and treatment outcomes could contribute to a personalized approach to treatment for individuals with NP.

Frequency of idiopathic intracranial hypertension with ultrasound in patients with fibromyalgia: Relation with function, central sensitization, and neuropathic pain.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of idiopathic intracranial hypertension (IIH) in fibromyalgia (FMS) patients by utilizing ultrasound to measure the optic nerve sheath diameter (ONSD), a marker of elevated intracranial pressure and also to investigate the relationship with function, fatigue, quality of life (QOL), central sensitization (CS) and neuropathic pain. METHODS: The study encompassed 80 female FMS patients and 75 healthy controls. Ultrasound was employed to measure the average ONSD in both groups. Conditions potentially elevating intracranial pressure were ruled out following neurological assessments. Pain (via visual analog scale, VAS), function (revised Fibromyalgia Impact Questionnaire, r-FIQ), QOL (Short Form-36, SF-36), fatigue (fatigue severity scale, FACIT), CS (Central Sensitization Scale), and neuropathic pain (Douleur Neuropathique-4) were evaluated. RESULTS: The average ONSD was significantly higher in the patient group than the control group. Patients with ONSD >5.5 mm consistent with IIH were categorized as Group 1 (n = 54, 67.5%), while those with a diameter of 5.5 mm and below-formed Group 2. VAS pain (p = .033) and FIQ-R scores (p = .033) were significantly higher in Group 1 than Group 2. Headache was found more common in Group 1. CONCLUSION: This study unveils a substantial occurrence (67.5%) of IIH in FMS patients, suggesting shared pathophysiological mechanisms contributing to symptoms like fatigue, headache, and cognitive dysfunction. Additionally, these findings implicate heightened functional impairment, CS, headache, and fatigue in FMS patients with IIH.

In subjects with chronic low back pain, does neuropathia exclusively correlated to neuronal compression? A correlation study of PainDETECT questionnaire and corresponding MRI and X-ray findings.

INTRODUCTION: Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP), nociceptive (NoP), and ambiguous pain. This study aimed to investigate the relationship between pain classification and lumbar intervertebral degenerative parameters obtained from imaging. METHODS: A cohort study was conducted involving 279 patients, aged 18 years and above, who completed PainDETECT questionnaires and underwent lumbar MRI and/or X-ray scans. RESULTS: The study included 102 patients with NoP, 78 with ambiguous pain, and 99 with NeP. The NeP group had lower mean age (58.21 vs. 53.63, p < 0.05) and higher mean numerical rating scale score (7.9 vs. 5.9, p < 0.001) compared to the NoP group. A negative correlation was found between PainDETECT scores and pelvic incidence (τ = - 0.177, p = 0.043). The NeP group exhibited significantly higher severity of foraminal stenosis (U = 18.962, p = 0.002), spinal stenosis (U = 14.481, p = 0.005), and Pfirrmann grade (U = 14.221, p = 0.028) compared to the NoP group. A higher proportion of NeP patients had intervertebral disk bulge (96% vs. 78% vs. 78%, p = 0.002) and high-intensity zones (51% vs. 41% vs. 19%, p < 0.001) compared to those with NoP and ambiguous pain. CONCLUSION: NeP, as determined by the PainDETECT questionnaire, is associated with more severe neural compression, increased presence of discogenic disease and inflammatory disk severity, and decreased pelvic incidence. This pioneering study establishes a connection between pathological findings and pain categorization, providing clinicians with valuable guidance for formulating tailored management plans and reducing the need for unnecessary pharmacotherapy, imaging, and non-targeted surgical interventions.

Functional Cerebral Neurovascular Mapping During Focused Ultrasound Peripheral Neuromodulation of Neuropathic Pain.

BACKGROUND: Nociceptive pain is required for healthy function, yet, neuropathic pain (disease or injury) can be severely debilitating. Though a wide-array of treatment options are available, they are often systemic and/or invasive. As a promising neuromodulation treatment, Focused ultrasound (FUS) is a noninvasive and highly spatially-targeted technique shown to stimulate neural activity, yet, effects on pain signaling are currently unknown. OBJECTIVE: Develop and validate a method for studying FUS nerve stimulation modulation of pain-evoked neural responses in vivo. METHODS: We developed a high-resolution functional ultrasound (fUS) method capable of mapping cortical responses in healthy and neuropathic pain mice in response to FUS neuromodulation treatment. RESULTS: FUS-evoked hemodynamic responses are correlated with the intensity of peripheral neuromodulation. We confirm functional connectivity is altered in neuropathic mice and demonstrate that FUS can modulate neuropathic pain-evoked hemodynamics. CONCLUSIONS: The findings presented herein provides evidence for an FUS-based nerve pain method and validates the fUS technique developed for monitoring pain-evoked hemodynamics. SIGNIFICANCE: We anticipate that the findings presented herein describe a noninvasive and flexible nerve modulation technique for pain mitigation, furthering evidence for clinical translation.

Higher Regional Gray Matter Volume and White Matter Integrity in Individuals With Central Neuropathic Pain After Spinal Cord Injury.

Spinal cord injury (SCI) is a debilitating neurological condition that often leads to central neuropathic pain (CNP). As the fundamental mechanism of CNP is not fully established, its management is one of the most challenging problems among people with SCI. To shed more light on CNP mechanisms, the aim of this cross-sectional study was to compare the brain structure between individuals with SCI and CNP and those without CNP by examining the gray matter (GM) volume and the white matter (WM) integrity. Fifty-two individuals with SCI-28 with CNP and 24 without CNP-underwent a magnetic resonance imaging (MRI) session, including a T1-weighted scan for voxel-based morphometry, and a diffusion-weighted imaging (DWI) scan for WM integrity analysis, as measured by fractional anisotropy (FA) and mean diffusivity (MD). We found significantly higher GM volume in individuals with CNP compared with pain-free individuals in the right superior (p < 0.0014) and middle temporal gyri (p < 0.0001). Moreover, individuals with CNP exhibited higher WM integrity in the splenium of the corpus callosum (p < 0.0001) and in the posterior cingulum (p < 0.0001), compared with pain-free individuals. The results suggest that the existence of CNP following SCI is associated with GM and WM structural abnormalities in regions involved in pain intensification and spread, and which may reflect maladaptive neural plasticity in CNP.

Peripheral Pain Captured Centrally: Altered Brain Morphology on MRI in Small Fiber Neuropathy Patients With and Without an SCN9A Gene Variant.

The current study aims to characterize brain morphology of pain as reported by small fiber neuropathy (SFN) patients with or without a gain-of-function variant involving the SCN9A gene and compare these with findings in healthy controls without pain. The Neuropathic Pain Scale was used in patients with idiopathic SFN (N = 20) and SCN9A-associated SFN (N = 12) to capture pain phenotype. T1-weighted, structural magnetic resonance imaging (MRI) data were collected in patients and healthy controls (N = 21) to 1) compare cortical thickness and subcortical volumes and 2) quantify the association between severity, quality, and duration of pain with morphological properties. SCN9A-associated SFN patients showed significant (P < .017, Bonferroni corrected) higher cortical thickness in sensorimotor regions, compared to idiopathic SFN patients, while lower cortical thickness was found in more functionally diverse regions (eg, posterior cingulate cortex). SFN patient groups combined demonstrated a significant (Spearman's ρ = .44-.55, P = .005-.049) correlation among itch sensations (Neuropathic Pain Scale-7) and thickness of the left precentral gyrus, and midcingulate cortices. Significant associations were found between thalamic volumes and duration of pain (left: ρ = -.37, P = .043; right: ρ = -.40, P = .025). No associations were found between morphological properties and other pain qualities. In conclusion, in SCN9A-associated SFN, profound morphological alterations anchored within the pain matrix are present. The association between itch sensations of pain and sensorimotor and midcingulate structures provides a novel basis for further examining neurobiological underpinnings of itch in SFN. PERSPECTIVE: Cortical thickness and subcortical volume alterations in SFN patients were found in pain hubs, more profound in SCN9A-associated neuropathy, and correlated with itch and durations of pain. These findings contribute to our understanding of the pathophysiological pathways underlying chronic neuropathic pain and symptoms of itch in SFN.

Focused Ultrasound Central Lateral Thalamotomy for the Treatment of Refractory Neuropathic Pain: Phase I Trial.

BACKGROUND AND OBJECTIVES: Magnetic resonance-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) has not yet been validated for treating refractory neuropathic pain (NP). Our aim was to assess the safety and potential efficacy of MRgFUS CLT for refractory NP. METHODS: In this prospective, nonrandomized, single-arm, investigator-initiated phase I trial, patients with NP for more than 6 months related to phantom limb pain, spinal cord injury, or radiculopathy/radicular injury and who had undergone at least one previous failed intervention were eligible. The main outcomes were safety profile and pain as assessed using the brief pain inventory, the pain disability index, and the numeric rating scale. Medication use and the functional connectivity of the default mode network (DMN) were also assessed. RESULTS: Ten patients were enrolled, with nine achieving successful ablation. There were no serious adverse events and 12 mild/moderate severity events. The mean age was 50.9 years (SD: 12.7), and the mean symptom duration was 12.3 years (SD: 9.7). Among eight patients with a 1-year follow-up, the brief pain inventory decreased from 7.6 (SD: 1.1) to 3.8 (SD: 2.8), with a mean percent decrease of 46.3 (SD: 40.6) (paired t -test, P = .017). The mean pain disability index decreased from 43.0 (SD: 7.5) to 25.8 (SD: 16.8), with a mean percent decrease of 39.3 (SD: 41.6) ( P = .034). Numeric rating scale scores decreased from a mean of 7.2 (SD: 1.8) to 4.0 (SD: 2.8), with a mean percent decrease of 42.8 (SD: 37.8) ( P = .024). Patients with predominantly intermittent pain or with allodynia responded better than patients with continuous pain or without allodynia, respectively. Some patients decreased medication use. Resting-state functional connectivity changes were noted, from disruption of the DMN at baseline to reactivation of connectivity between DMN nodes at 3 months. CONCLUSION: MRgFUS CLT is feasible and safe for refractory NP and has potential utility in reducing symptoms as measured by validated pain scales.

Altered intrinsic brain activity in patients with neuropathic pain after brachial plexus avulsion.

OBJECTIVE: This study aimed to investigate brain activity changes in patients suffering from neuropathic pain (NP) following brachial plexus avulsion (BPA). METHODS: Fifteen patients with NP following BPA and eight healthy participants (HP) were recruited for this study. All participants underwent examination using resting-state functional MRI. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were calculated and compared between the BPA group, left-BPA subgroup, right-BPA subgroup, and the HP group using independent samples t-tests. RESULTS: In the BPA group, there were notable increases in ALFF/ReHo observed in the left rolandic operculum, insula, and supramarginal gyrus, while decreases were observed in the left paracentral lobule, fusiform gyrus, calcarine fissure and surrounding cortex, lingual gyrus, precuneus, as well as the bilateral anterior/median cingulate and paracingulate gyri, supplementary motor area, and cerebellum. In the left-BPA subgroup, elevated ALFF/ReHo levels were identified in the left middle/inferior frontal gyri, rolandic operculum, and supramarginal gyrus, with corresponding decreases in the left calcarine fissure and surrounding cortex, inferior occipital gyrus, fusiform gyrus, lingual gyrus, as well as the bilateral anterior/median cingulate and paracingulate gyri, postcentral gyri, supplementary motor area, paracentral lobules, and cerebellum. The right-BPA subgroup displayed increased ALFF/ReHo in the left frontal lobe, rolandic operculum, insula, fusiform gyrus, and lingual gyrus, as well as the right cerebellum. Conversely, decreases in ALFF/ReHo were observed in the bilateral anterior/median cingulate and paracingulate gyri, calcarine fissure and surrounding cortex, cuneus, and occipital lobes. CONCLUSIONS: The NP after BPA caused spontaneous activity changes in brain regions associated with linguistic, visual, somatosensory, and motor coordination and processing function. The majority of these abnormal areas were situated in the left cerebral hemisphere, while the effect of cingulate gyri and cerebellum seemed to be bilateral.

Ultrasound appearance and targeted therapy of symptomatic neural lesions in the breast and chest wall after breast cancer surgery.

AIM: To evaluate the feasibility of ultrasound (US) in identification of nerve lesions after breast cancer surgery in patients with neuropathic pain and assess the effect of a targeted US-guided therapy. MATERIAL AND METHODS: Patients with neuropathic pain after breast cancer surgery underwent US examination. Nerve lesions identified by US were treated by a US-guided application of a mixture of local anesthetics and corticoids. The patients reported pain relief on a 100-point scale (0% = no effect, 100% = complete relief) and its duration in the next 18 months. RESULTS: We performed 17 interventions in 11 women. A neuroma was observed in 2 patients, edema of the nerve in 5 patients, and scarring across the nerve in 4 patients. The affected nerves were the intercostobrachial nerve (5 patients), the long thoracic nerve (4), cutaneous branch of the pectoral nerve (1), and both the intercostobrachial and the long thoracic nerve (1). After 15 (88%) interventions, the patients reported relief (55±32%) with a median duration of 3 months (0.5-18 months). CONCLUSION: In patients after breast cancer surgery, ultrasound can reliably identify small painful neural lesions which can be efficiently treated by ultrasound-guided intervention.

A rs-fMRI study of functional connectivity changes between thalamus and postcentral gyrus in patients with neuropathic pain after brachial plexus avulsion.

BACKGROUND: The neuropathic pain (NPP) after brachial plexus avulsion (BPA) is common and difficult to cure, and thalamus and postcentral gyrus have been accepted to be the key nodes of mechanisms and pathways for pain. However, little attention has been paid on the thalamus-postcentral gyrus functional connectivity changes in NP patients after BPA. METHODS: Eighteen patients with NPP after BPA and twenty age and gender matched healthy controls were enrolled and underwent resting-state functional MRI (rs-fMRI) scans in this study. The Pearson's r-value of functional connection (bilateral thalamus and postcentral gyrus as regions of interest) was generated and examined using two sample t-test. The linear regression analysis was used to select possible related factors, and multiple linear regression of the possible predictors was used to identify the variables that significantly predicted Visual Analogue Score (VAS). RESULTS: The standardized Pearson r-values of the left thalamus-right thalamus, left thalamus-left postcentral gyrus, left thalamus-right postcentral gyrus, right thalamus-left postcentral gyrus and right thalamus-right postcentral gyrus in the control group were 0.759 ± 0.242, 0.358 ± 0.297, 0.383 ± 0.270, 0.317 ± 0.295 and 0.333 ± 0.304, respectively. And the corresponding standardized Pearson r-values in patients group were 0.510 ± 0.224,0.305 ± 0.212,0.281 ± 0.225,0.333 ± 0.193 and 0.333 ± 0.210, respectively. The functional connectivity strength of the left thalamus-right thalamus in control group was significantly higher than that in the patients group (P < 0.05). Linear regression analysis showed that the functional connectivity strength of the left thalamus-right thalamus was negatively correlated with the patients' VAS score (P < 0.05). CONCLUSIONS: NPP patients after BPA had a significant pain-related bilateral thalamus functional connection reorganization, with the purpose to limit the pain signal inputs within the unilateral cerebral hemisphere.

Brain imaging signatures of neuropathic facial pain derived by artificial intelligence.

Advances in neuroimaging have permitted the non-invasive examination of the human brain in pain. However, a persisting challenge is in the objective differentiation of neuropathic facial pain subtypes, as diagnosis is based on patients' symptom descriptions. We use artificial intelligence (AI) models with neuroimaging data to distinguish subtypes of neuropathic facial pain and differentiate them from healthy controls. We conducted a retrospective analysis of diffusion tensor and T1-weighted imaging data using random forest and logistic regression AI models on 371 adults with trigeminal pain (265 classical trigeminal neuralgia (CTN), 106 trigeminal neuropathic pain (TNP)) and 108 healthy controls (HC). These models distinguished CTN from HC with up to 95% accuracy, and TNP from HC with up to 91% accuracy. Both classifiers identified gray and white matter-based predictive metrics (gray matter thickness, surface area, and volume; white matter diffusivity metrics) that significantly differed across groups. Classification of TNP and CTN did not show significant accuracy (51%) but highlighted two structures that differed between pain groups-the insula and orbitofrontal cortex. Our work demonstrates that AI models with brain imaging data alone can differentiate neuropathic facial pain subtypes from healthy data and identify regional structural indicates of pain.

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

Many individuals with spinal cord injury live with debilitating chronic pain that may be neuropathic, nociceptive, or a combination of both in nature. Identification of brain regions demonstrating altered connectivity associated with the type and severity of pain experience may elucidate underlying mechanisms, as well as treatment targets. Resting state and sensorimotor task-based magnetic resonance imaging data were collected in 37 individuals with chronic spinal cord injury. Seed-based correlations were utilized to identify resting state functional connectivity of regions with established roles in pain processing: the primary motor and somatosensory cortices, cingulate, insula, hippocampus, parahippocampal gyri, thalamus, amygdala, caudate, putamen, and periaqueductal gray matter. Resting state functional connectivity alterations and task-based activation associated with individuals' pain type and intensity ratings on the International Spinal Cord Injury Basic Pain Dataset (0-10 scale) were evaluated. We found that intralimbic and limbostriatal resting state connectivity alterations are uniquely associated with neuropathic pain severity, whereas thalamocortical and thalamolimbic connectivity alterations are associated specifically with nociceptive pain severity. The joint effect and contrast of both pain types were associated with altered limbocortical connectivity. No significant differences in task-based activation were identified. These findings suggest that the experience of pain in individuals with spinal cord injury may be associated with unique alterations in resting state functional connectivity dependent upon pain type.

Magnetic resonance-guided focused ultrasound central lateral thalamotomy against chronic and therapy-resistant neuropathic pain: retrospective long-term follow-up analysis of 63 interventions.

OBJECTIVE: Medial thalamotomies were introduced in the late 1940s. Pain relief was shown to be achieved for all body locations. With some exceptions, these early relatively small series showed frequent, more or less complete recurrence of the original pain. The posterior part of the central lateral nucleus in the human medial thalamus was identified in the 1990s using multiarchitectonic studies and intraoperative single-cell recordings and was confirmed as a surgical target. This retrospective patient series extended over 11 years. Its goal was to demonstrate the efficacy and risk profile of the MR-guided focused ultrasound (MRgFUS) central lateral thalamotomy (CLT) against chronic and therapy-resistant neuropathic (i.e., neurogenic) pain. METHODS: In this single-center, nonrandomized retrospective cross-sectional analysis of consecutive patients, 63 consecutive MRgFUS CLT interventions were performed in 55 patients. RESULTS: The mean follow-up duration was 55 months. A total of 112 CLT targets were performed, and the CLT was applied bilaterally in 48 patients and contralateral to their pain in 7 patients. Repeat MRgFUS interventions were performed in 8 patients. One serious adverse event with numbness of the upper lip was recorded. The mean pain relief rated by patients was 42% ± 32% at 3 months, 43% ± 36% at 1 year, and 42% ± 37% at the last follow-up (n = 63). The proportions of cases with ≥ 30% pain relief were 65% at 3 months, 63% at 1 year, and 61% at the last follow-up. Good outcomes (≥ 50% pain relief) were found in 54% of patients at 3 months, 49% at 1 year, and 51% at the last follow-up. The reduction in mean VAS scores showed similar percentage reductions as those for pain relief (-41% for continuous pain and -49% for pain attacks) at the 1-year follow-up. The mean frequency of pain attacks was reduced by 92%. Allodynia was reduced or suppressed in 68% of patients and never appeared de novo after MRgFUS CLT. CONCLUSIONS: These results suggest that MRgFUS CLT against neuropathic pain is a safe approach and its results are stable over time. At a mean follow-up duration of 55 months, the mean pain relief was 42% and more than 50% of patients still reported ≥ 50% pain relief. Patients with classical and idiopathic trigeminal neuralgia reported a higher mean pain relief compared with the whole patient group.

Limbic Connectivity Underlies Pain Treatment Response in Small-Fiber Neuropathy.

OBJECTIVE: Small-fiber neuropathy (SFN) is characterized by neuropathic pain due to degeneration of small-diameter nerves in the skin. Given that brain reorganization occurs following chronic neuropathic pain, this study investigated the structural and functional basis of pain-related brain changes after skin nerve degeneration. METHODS: Diffusion-weighted and resting-state functional MRI data were acquired from 53 pathologically confirmed SFN patients, and the structural and functional connectivity of the pain-related network was assessed using network-based statistic (NBS) analysis. RESULTS: Compared with age- and sex-matched controls, the SFN patients exhibited a robust and global reduction of functional connectivity, mainly across the limbic and somatosensory systems. Furthermore, lower functional connectivity was associated with skin nerve degeneration measured by reduced intraepidermal nerve fiber density and better therapeutic response to anti-neuralgia medications, particularly for the connectivity between the insula and the limbic areas including the anterior and middle cingulate cortices. Similar to the patterns of functional connectivity changes, the structural connectivity was robustly reduced among the limbic and somatosensory areas, and the cognition-integration areas including the inferior parietal lobule. There was shared reduction of structural and functional connectivity among the limbic, somatosensory, striatal, and cognition-integration systems: (1) between the middle cingulate cortex and inferior parietal lobule and (2) between the thalamus and putamen. These observations indicate the structural basis underlying altered functional connectivity in SFN. INTERPRETATION: Our findings provide imaging evidence linking structural and functional brain dysconnectivity to sensory deafferentation caused by peripheral nerve degeneration and therapeutic responses for neuropathic pain in SFN. ANN NEUROL 2023;93:655-667.

Ultrasound-guided percutaneous peripheral nerve stimulation for chronic refractory neuropathic pain: a unique series.

During the last two decades, with the advent of recent technology, peripheral nerve stimulation has become an appealing modality at the forefront of pain management. In this case series, we document the clinical rationale and technical considerations on three of the most challenging cases, refractory to previous interventions, that were treated by our team with an ultrasound-guided percutaneous peripheral nerve stimulator targeting the musculocutaneous, bilateral greater occipital and subcostal nerves. At the 6-month follow-up, all patients experienced greater than 50% relief of baseline pain, with a near-complete resolution of pain exacerbations. Furthermore, to our knowledge, this is the first report of an ultrasound-guided percutaneous technique of a peripheral nerve stimulator targeting the musculocutaneous and subcostal nerves.

Peripheral nerve stimulation is a new tool used in the treatment of peripheral nerve pain. In this study, we share our experience using this technology in three unusual, difficult-to-treat chronic nerve pain presentations, targeting the musculocutaneous, bilateral greater occipital and subcostal nerves. All patients were asked about how pain levels had changed since the peripheral nerve stimulation device had been implanted. In every case, patients reported a decline in their pain level from day one. After 6 months of peripheral nerve stimulator use, all patients reported a greater than 50% pain relief.