New daily persistent headache (NPDH) is a rare primary headache that is highly disabling. The pathophysiology of NDPH is still unclear, and we aimed to reveal the underlying mechanism of NDPH through functional magnetic resonance imaging (fMRI) analysis.In this cross-sectional study, thirty patients with NDPH and 30 healthy controls (HCs) were recruited. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the GE 3.0 T system. We performed ReHo, ALFF (conventional band: 0.01-0.08 Hz, slow-5: 0.01-0.027 Hz, slow-4: 0.027-0.073 Hz) and seed-based to the whole brain functional connectivity (FC) analysis in the NDPH and HC groups. The sex difference analysis of ReHo, ALFF, and FC values was conducted in the NDPH group. We also conducted Pearson's correlation analysis between ReHo, ALFF, FC values and clinical characteristics (pain intensity, disease duration, HIT-6, GAD-7, PHQ-9, and PSQI scores).Both increased ReHo (PFWE-corr = 0.012) and ALFF values (0.01-0.08 Hz, PFWE-corr = 0.009; 0.027-0.073 Hz, PFWE-corr =0.044) of the left middle occipital gyrus (MOG_L) were found in the NDPH group compared to the HC group. There was no significant difference in FC maps between the two groups. Compared to the HC group, no difference was found in ReHo (p = 0.284), ALFF (p = 0.246), and FC (p = 0.118) z scores of the MOG_L in the NDPH group. There was also no sex difference in ReHo (p = 0.288), ALFF (p = 0.859), or FC z score (p = 0.118) of the MOG_L in patients with NDPH. There was no correlation between ReHo, ALFF, FC z scores and clinical characteristics after Bonferroni correction (p < 0.05/18).Patients with NDPH may have abnormal activation of the visual system. Abnormal visual activation may occur mainly in higher frequency band of the classical band. No sex differences in brain activity were found in patients with NDPH. 

/pdf/alterations-in-regional-homogeneity-and-multiple-frequency-1zso2434.pdf

Alterations in regional homogeneity and multiple frequency amplitudes of low-frequency fluctuation in patients with new daily persistent headache: a resting-state functional magnetic resonance imaging study

Abstract The skeleton plays a fundamental role in the maintenance of organ function and daily activities. The insulin‐like growth factor (IGF) family is a group of polypeptide substances with a pronounced role in osteoblast differentiation, bone development, and metabolism. Disturbance of the IGFs and the IGF signaling pathway is inextricably linked with assorted developmental defects, growth irregularities, and jeopardized skeletal structure. Recent findings have illustrated the significance of the action of the IGF signaling pathway via growth factors and receptors and its interactions with dissimilar signaling pathways (Wnt/β‐catenin, BMP, TGF‐β, and Hh/PTH signaling pathways) in promoting the growth, survival, and differentiation of osteoblasts. IGF signaling also exhibits profound influences on cartilage and bone development and skeletal homeostasis via versatile cell–cell interactions in an autocrine, paracrine, and endocrine manner systemically and locally. Our review summarizes the role and regulatory function as well as a potentially integrated gene network of the IGF signaling pathway with other signaling pathways in bone and cartilage development and skeletal homeostasis, which in turn provides an enlightening insight into visualizing bright molecular targets to be eligible for designing effective drugs to handle bone diseases and maladies, such as osteoporosis, osteoarthritis, and dwarfism. 

<scp>IGF</scp> signaling pathway in bone and cartilage development, homeostasis, and disease

BACKGROUND
Effective pain control of herpes zoster ophthalmicus (HZO) is not only essential to attenuate the clinical symptoms but to reduce the risk of postherpetic neuralgia development. Recently, neuromodulation therapy has been one promising option for neuropathic pain and increasingly applied in management of zoster-related pain. One key factor of neuromodulation treatment is the therapeutic site for the impaired nerves. In this study we aim to investigate one novel dual-neuromodulation strategy, targeting the level of the peripheral branch and trigeminal ganglion, in the pain management of HZO.


METHODS
Dual neuromodulation strategy combining short-term peripheral nerve stimulation (PNS) with pulsed radiofrequency (PRF) of trigeminal ganglion was compared with single PNS treatment for HZO-related pain. Clinical recordings of patients were retrospectively reviewed. The primary outcome was the pain severity, assessed by the visual analogue scale (VAS) before and after neuromodulation therapy.


RESULTS
PNS achieved significant relief of pain with or without PRF treatment before discharge, which provided enduring therapeutic effect up to 12-month follow-up. The mean reduction of VAS was 6.7 ± 1.4 in dual modulation therapy (n = 13) at last follow-up and 5.4 ± 1.5 in PNS subgroup (n = 20), respectively. Moreover, dual modulation strategy provided better control of pain compared with PNS therapy alone at each time point.


CONCLUSION
It is feasible and effective to combine the PNS and PRF in pain management of HZO. This novel dual modulation strategy of trigeminal pathway may provide additional therapeutic effects of pain symptoms in HZO population.

Dual-neuromodulation strategy in pain management of herpes zoster ophthalmicus: retrospective cohort study and literature review.

Background The neurocutaneous disease caused by the reactivation of varicella-zoster virus (VZV) is called herpes zoster (HZ). The virus remains in the spinal cord back root after the chickenpox disappears. Diminished immune function can reactivate VZV, causing severe neuropathic pain that can last for months or even years, leading to postherpetic neuralgia (PHN), which severely affects the patient’s quality of life. Much literature compares various cytokine levels in the body fluids HZ and PHN patients; however, no studies comprehensively evaluate them. Methods The Cochrane Library, PubMed, Web of Science, and Medline were screened for studies on cytokine levels in body fluids of HZ and PHN patients in the English language. Healthy individuals were selected as the control group, and the standardized mean difference (SMD) between the case and control groups was imputed using a fixed-effects or random-effects model and expressed as a 95% confidence interval (CI). The Newcastle-Ottawa Scale (NOS) was used to assess article quality. Results This meta-analysis included 13 articles with 1373 participants. Compared with the control group, the HZ group had significantly higher levels of interleukin (IL)-4, IL-6, IL-10, Hcy, and C-reactive protein (CRP), whereas the levels of CD3+ T and CD4+ T lymphocytes were reduced. Additionally, PHN patients had significantly higher levels of IL-6 and IL-1β compared with the control group. Conclusion This meta-analysis provides compelling evidence that CRP, Hcy, IL-1β, IL-4, IL-6, IL-8, and IL-10 are associated with the genesis and development of HZ and PHN. These markers can be used to improve the diagnosis and treatment of these diseases.Furthermore, for making the results more convincing, it is necessary to harmonize sample acquisition techniques and analytical methods and also require larger, more rigorously designed studies with broader subgroups and sex/age-matched controls.

Humoral Cytokine Levels in Patients with Herpes Zoster: A Meta-Analysis

Background Chronic low back pain (cLBP) has been associated with alterations in brain functional connectivity (FC) but based upon heterogeneous populations and single network analyses. Our goal is to study a more homogeneous cLBP population and focus on multiple cross-network (CN) connectivity analysis. We hypothesize that within this population: 1) altered CN FC, involving emotion and reward/aversion functions are related to their pain levels and 2) altered relationships are dependent upon pain phenotype (constant neuropathic vs intermittent pain). Methods In this case series, resting state fcMRI scans were obtained over a study duration of 60 months from 23 patients (13 constant neuropathic and 10 intermittent pain) with Persistent Spinal Pain Syndrome (PSPS Type 2) being considered for spinal cord stimulation (SCS) therapy at a single academic center. Images were acquired using a Discovery MR750 GE scanner. During the resting state acquisitions, they were asked to close their eyes and relax. The CN analysis was performed on 7 brain networks and compared to age-matched controls. Linear regression was used to test the correlation between CN connectivity and pain scores. Results CN FC involving emotion networks (STM: striatum network index) was significantly lower than controls in all patients, regardless of pain phenotype (P < 0.003). Pain levels were positively correlated with emotional FC for intermittent pain but negatively correlated for constant pain. Conclusion This is the first report of 1) altered CN FC involving emotion/reward brain circuitry in 2) a homogeneous population of cLBP patients with 3) two different pain phenotypes (constant vs intermittent) in PSPS Type 2 patients being considered for SCS. FC patterns were altered in cLBP patients as compared to controls and were characteristic for each pain phenotype. These data support fcMRI as a potential and objective tool in assessing pain levels in cLBP patients with different pain phenotypes.

Distinct Functional Connectivity Patterns for Intermittent Vs Constant Neuropathic Pain Phenotypes in Persistent Spinal Pain Syndrome Type 2 Patients

Introduction The efficacy of short-term spinal cord stimulation (stSCS) as a treatment for neuropathic pain in patients with postherpetic neuralgia (PHN) has already been validated. However, the potential alterations in brain functionality that are induced by such treatment have yet to be completely elucidated. Methods This study use resting-state functional magnetic resonance imaging (rs-fMRI) to detect the changes in regional homogeneity (ReHo) and degree centrality (DC) related to stimulator-induced pain relief in patients with PHN. A total of 10 patients with PHN underwent an MRI protocol at baseline and after stSCS. Alterations in ReHo and DC were then compared between baseline and after stSCS. We investigated the relationship between clinical parameters and functional changes in the brain. Results Clinical parameters on pain, emotion, and sleep quality were correlated with ReHo and DC. ReHo and DC were significantly altered in the middle temporal gyrus, precuneus, superior frontal gyrus, supramarginal gyrus, inferior parietal lobule, rolandic operculum, middle occipital gyrus, superior parietal gyrus, and the precentral gyrus after stSCS. A significant correlation was detected between ReHo changes in the middle occipital gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality. A significant negative correlation was detected between DC changes in the middle temporal gyrus, rolandic operculum, supramarginal gyrus, precuneus, inferior parietal gyrus, and changes in pain, emotion, and sleep quality. Conclusion This study found that stSCS is able to induce ReHo and DC changes in patients with PHN, thus suggesting that stSCS can change brain function to alleviate pain, sleep, and emotional disorder.

/pdf/alterations-in-local-activity-and-functional-connectivity-in-2will9it.pdf

Alterations in local activity and functional connectivity in patients with postherpetic neuralgia after short-term spinal cord stimulation

Objective: This study aimed to investigate the effect of therapy with peripheral nerve stimulation (PNS) and pulsed radiofrequency (PRF) combined or PNS and PRF separately in patients with herpes zoster ophthalmicus (HZO). Materials and Methods: This cohort study included 106 cases of HZO. Three groups were identified according to the type of treatment received: combination therapy (PNS+PRF) (n=38), PRF (n=37), and PNS (n=31). The observations at 0, 1, 2, and 4 weeks; 3 and 6 months; and 1 and 2 years after the operation were analyzed. Observations at each follow-up included baseline characteristics, Numerical Rating Scale (NRS) and the Pittsburgh Sleep Quality Index (PSQI), concomitant pain medication usage, relapse rate, and adverse events. Results: The postoperative NRS of all 3 groups were significantly lower than preoperative scores. The PSQI of the 3 groups was significantly improved postoperatively, and the concomitant pain medication gradually decreased. Regarding long-term efficacy, the pain NRS and PSQI scores of the PNS+PRF and PNS groups were significantly lower than those of the PRF group (P<0.05), and the relapse rate of the PRF group was higher than that of the PNS+PRF and PNS groups (P<0.05). No significant difference was observed between the PNS+PRF and the PNS groups. Conclusion: Both PNS and PRF treatment of HZO can decrease the pain score, yielding no serious complications. The combination of PNS and PRF or PNS alone resulted in more significant pain relief than treatment with PRF alone. Thus, PNS therapy may be a better treatment option for HZO.

Comparison of the Efficacy of Short-term Peripheral Nerve Stimulation and Pulsed Radiofrequency for Treating Herpes Zoster Ophthalmicus Neuralgia

Bone cancer pain (BCP) is one of the most ubiquitous and refractory symptoms of cancer patients that needs to be urgently addressed. Substantial studies have revealed the pivotal role of Cav3.2 T-type calcium channels in chronic pain, however, its involvement in BCP and the specific molecular mechanism have not been fully elucidated. The expression levels of Cav3.2, insulin-like growth factor 1(IGF-1), IGF-1 receptor (IGF-1R) and hypoxia-inducible factor-1α (HIF-1α) were detected by Western blot in tissues and cells. X-ray and Micro CT used to detect bone destruction in rats. Immunofluorescence was used to detect protein expression and spatial location in the spinal dorsal horn. Electrophoretic mobility shift assay used to verify the interaction between HIF-1α and Cav3.2. The results showed that the expression of Cav3.2 channel was upregulated and blockade of this channel alleviated mechanical allodynia and thermal hyperalgesia in BCP rats. Additionally, inhibition of IGF-1/IGF-1R signaling not only reversed the BCP-induced upregulation of Cav3.2 and HIF-1α, but also decreased nociceptive hypersensitivity in BCP rats. Inhibition of IGF-1 increased Cav3.2 expression levels, which were abolished by pretreatment with HIF-1α siRNA in PC12 cells. Furthermore, nuclear HIF-1α bound to the promoter of Cav3.2 to regulate the Cav3.2 transcription level, and knockdown of HIF-1α suppresses the IGF-1-induced upregulation of Cav3.2 and pain behaviors in rats with BCP. These findings suggest that spinal Cav3.2 T-type calcium channels play a central role during the development of bone cancer pain in rats via regulation of the IGF-1/IGF-1R/HIF-1α pathway. 

Cav3.2 T-Type calcium channels downregulation attenuates bone cancer pain induced by inhibiting IGF-1/HIF-1α signaling pathway in the rat spinal cord

Objective: To investigate the correlation between balloon volume and Meckel's cave size during percutaneous puncture microballoon compression (PMC) for trigeminal neuralgia and the influence of the compression coefficient (the ratio of balloon volume/Meckel's cave size) on the prognosis. Methods: Seventy-two patients (28 males and 44 females) aged (62±11) years who underwent PMC under general anesthesia for trigeminal neuralgia in the First Affiliated Hospital of Zhengzhou University from February 2018 to October 2020 were retrospectively collected. All patients underwent preoperative cranial magnetic resonance imaging (MRI) to measure Meckel's cave size, intraoperative balloon volume was recorded, and the compression coefficient was calculated. Follow-up visits were performed preoperatively (T0) and 1 d (T1), 1 month (T2), 3 months (T3), and 6 months (T4) postoperatively, either in the outpatient clinic or by telephone, and the Barrow Neurological Institute pain scale (BNI-P) score, the Barrow Neurological Institute facial numbness (BNI-N) score and the occurrence of complications were recorded and compared at each time point. Patients were divided into 3 groups according to different prognoses: patients in group A (n=48) were with no recurrence of pain and mild facial numbness, patients in group B (n=19) were with no recurrence of pain but severe facial numbness, while those in group C (n=5) had recurrence of pain. The differences in balloon volume, Meckel's cave size, and compression coefficient were compared among the three groups, and the correlation between balloon volume and Meckel's cave size in each group was analyzed by Pearson correlation. Results: The effective rate of PMC for trigeminal neuralgia was 93.1% (67/72). At time points from T0 to T4, patients had BNI-P scores [M (Q1, Q3)] of 4.5 (4.0, 5.0), 1.0 (1.0, 1.0), 1.0 (1.0, 1.0), 1.0 (1.0, 1.0) and 1.0 (1.0, 1.0), and BNI-N scores [M (Q1, Q3)] of 1.0 (1.0, 1.0), 4.0 (3.0, 4.0), 3.0 (3.0, 4.0), 3.0 (2.0, 4.0) and 2.0 (2.0, 3.0), respectively. Compared with those at T0, patients had lower BNI-P scores and higher BNI-N scores from T1 to T4 (all P<0.05). In all patients, group A, group B, and group C, the balloon volume was (0.65±0.15), (0.67±0.15), (0.59±0.15) and (0.67±0.17) cm3, respectively, with no statistically significant difference (P>0.05), while the Meckel's cave size was (0.42±0.12), (0.44±0.11), (0.32±0.07), and (0.57±0.11) cm3, with a statistically significant difference (P<0.001). The balloon volumes and Meckel's cave sizes were all linearly and positively correlated (r=0.852, 0.924, 0.937 and 0.969, all P<0.05). The compression coefficient in group A, B and C was (1.54±0.14), (1.84±0.18) and (1.18±0.10), respectively, with a statistically significant difference (P<0.001). There were no serious intraoperative complications such as death, diplopia, arteriovenous fistula, cerebrospinal fluid leak, and subarachnoid hemorrhage. Conclusions: Intraoperative balloon volume during PMC for trigeminal neuralgia is linearly and positively correlated with the volume of the patient's Meckel's cave. The compression coefficient varies among patients with different prognoses and the compression coefficient may be a factor affecting the patient's prognosis.

[Correlation between balloon volume and Meckel's cave size and its influence of percutaneous microballoon compression for trigeminal neuralgia].

Epidural hematoma with the intermediate recovery period: A rare severe complication of spinal cord stimulation.

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