Cord Level Research Articles

Thoracic spinal arachnoid web and syringomyelia with rostral expansion to the first cervical spinal cord level: Case report.

Introduction and importanceA spinal arachnoid web is a rare pathology that has been associated with the development of syringomyelia. Syrinx expansion can occur, which can result in the development of new symptoms. In the current literature, the farthest rostral expansion of the associated syrinx has been to the C3 spinal level.Case presentationWe present a 49-year-old Hispanic male with a thoracic spinal arachnoid web and an associated syrinx spanning from C1 to T7 spinal level. The patient developed upper extremities radicular symptoms that worsened over time. He underwent surgical management with T6–8 laminectomy and excision of the web. Postoperative follow-up evaluations demonstrated progressive clinical improvement with eventual resolution of symptoms and syringomyelia.Clinical discussionSyringomyelia secondary to a thoracic spinal arachnoid web is a progressive disease that can expand rostrally to the C1 spinal level. The clinical presentation usually involves the lower extremities. However, if the upper thoracic or cervical spinal cord is involved, patients can also present symptoms in the upper extremities. Management usually involves surgical excision of the web in order to decompress the subarachnoid space and restore the normal cerebrospinal fluid (CSF) flow.ConclusionOur case suggests that syringomyelia secondary to a spinal arachnoid web may continuously expand with concomitant worsening of symptoms. However, surgical resection is curative with possible remission of symptoms and normalization of spinal anatomy.

Spontaneous pain as a challenge of research and management in chronic pain.

Spontaneous pain occurring without apparent external stimuli, is a significant complaint of individuals with chronic pain whose mechanisms, somewhat surprisingly, remain poorly understood. Over the past decades, neuroimaging studies start to reveal brain activities accompanying spontaneous pain. Meanwhile, a variety of animal models and behavioral tests have been established, including non-reflexive tests and free-choice tests, which have been shown to be effective in assessing spontaneous pain. For the spontaneous pain mechanisms, multiple lines of research mainly focus on three aspects: (1) sensitization of peripheral nociceptor receptors and ion channels, (2) spontaneous neuronal firing and abnormal activity patterns at the dorsal root ganglion and spinal cord level, (3) functional and structural alterations in the brain, particularly the limbic system and the medial pain pathway. Despite accumulating evidence revealing distinct neuronal mechanisms from evoked pain, we are still far from full understanding of spontaneous pain, leaving a big gap between bench and bedside for chronic pain treatment. A better understanding of the neural processes in chronic pain, with specific linkage as to which anatomical structures and molecules related to spontaneous pain perception and comorbidities, will greatly improve our ability to develop novel therapeutics.

Brown sequard syndrome as a manifestation of acute spontaneous spinal haematoma: A diagnostic challenge

Brown-Sequard Syndrome (BSS) is a neurological disorder caused by hemisection lesion of the spinal cord. BSS causes can be dichotomized in traumatic and atraumatic, and they can include vascular causes, as ischemia or haemorrhage. We describe the case of a 52-year-old woman presenting with limbs paraesthesia and right leg hyposthenia, associated with cervical acute nontraumatic pain (C6-C7 level). Neurological consultant was requested with a suspicious of vertebral artery dissection: clinical examination revealed right leg flaccid weakness, loss of pain and temperature sensation in left hemisoma, hypopallesthesia of right limbs and T1-T2 sensory level. Those symptoms were suggestive of a Brown Sequard Syndrome. MRI showed an epidural haematoma compressing spinal cord, associated with abnormal signal to C6-C7 and D1 level of spinal cord. Urgent laminectomy and evacuation were performed. Neurological symptoms improved avoiding permanent paraplegia

A CASE REPORT OF PEDIATRIC POST COVID ACUTE TRANSVERSE MYELITIS

Acute transverse myelitis (TM) is a rare acquired neuro-immune spinal cord disorder that can present with the rapid onset of weakness, sensory alterations, and bowel or bladder dysfunction. Pediatric post-infectious acute transverse myelitis presents with a myriad of motor, sensory and autonomic involvement disturbances at the spinal cord level without any significant disturbances in the brain. Few cases have been reported worldwide and post covid proven cases are around 8 in the pediatric population worldwide. Early initiation of treatment with pulse therapy of steroids and prompt recognition can give promising results in the pediatric population. Hereby presented is a similar case, post infectious, COVID antibody proven.

Vitamin D Levels in Pregnant Women Do Not Affect Neonatal Bone Strength.

Vitamin D plays a key role in regulating calcium and phosphate metabolism. However, whether maternal vitamin D levels affect fetal bone strength is unclear. This study assessed correlations between maternal 25(OH)D status and neonatal bone strength 25(OH)D levels, these were measured in the maternal and infant cord blood of 81 mother–infant dyads. Bone strength was measured using a quantitative ultrasound (QUS) of tibial bone speed of sound (SOS). Maternal vitamin D intake, medical history and lifestyle were evaluated from questionnaires. Maternal 25(OH)D levels were deficient (<25 nmol/L) in 24.7%, insufficient (25–50 nmol/L) in 37% and sufficient (>50 nmol/L) in 38.3%. The maternal and cord blood 25(OH)D levels correlated (r = 0.85, p < 0.001). Cord blood levels (57.9 ± 33.5 nmol/L) were higher than the maternal blood levels (46.3 ± 23.2: p < 0.001). The mean SOS was 3042 ± 130 m/s. The neonatal SOS and 25(OH)D levels were not correlated. The mean bone SOS levels were comparable in the three maternal and cord blood 25(OH)D groups. No correlation was found between the maternal 25(OH)D levels and the neonatal anthropometrics. Although the 25(OH)D levels were higher in Jewish mothers than they were in Muslim mothers (51.1 ± 22.6 nmol/L vs. 24 ± 14.7 nmol/L, respectively: p = 0.002) and in those who took supplemental vitamin D, the bone SOS levels were comparable. In conclusion, maternal vitamin D levels correlate with cord levels but do not affect bone strength or growth parameters.

Spinal CCK1 Receptors Contribute to Somatic Pain Hypersensitivity Induced by Malocclusion via a Reciprocal Neuron-Glial Signaling Cascade

Recent studies have shown that the incidence of chronic primary pain including temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS) often exhibit comorbidities. We recently reported that central sensitization and descending facilitation system contributed to the development of somatic pain hypersensitivity induced by orofacial inflammation combined with stress. The purpose of this study was to explore whether TMD caused by unilateral anterior crossbite (UAC) can induce somatic pain hypersensitivity, and whether the cholecystokinin (CCK) receptor-mediated descending facilitation system promotes hypersensitivity through neuron-glia cell signaling cascade. UAC evoked thermal and mechanical pain hypersensitivity of the hind paws from day 5 to 70 that peaked at week 4 post UAC. The expression levels of CCK1 receptors, interleukin-18 (IL-18) and IL-18 receptors (IL-18R) were significantly up-regulated in the L4 to L5 spinal dorsal horn at 4 weeks post UAC. Intrathecal injection of CCK1 and IL-18 receptor antagonists blocked somatic pain hypersensitivity. IL-18 mainly co-localized with microglia, while IL-18R mainly co-localized with astrocytes and to a lesser extent with neurons. These findings indicate that the signaling transduction between neurons and glia at the spinal cord level contributes to the descending pain facilitation through CCK1 receptors during the development of the comorbidity of TMD and FMS. PerspectiveCCK1 receptor-dependent descending facilitation may mediate central mechanisms underlying the development of widespread somatic pain via a reciprocal neuron-glial signaling cascade, providing novel therapeutic targets for the clinical treatment of TMD and FMS comorbidities.

NFB-01. Central nervous system tumors in Von Hippel-Lindau multisystem disorder: are there preventive approaches to escape tumor initiation at a young age?

In pediatric neuro-oncology, the likelihood of an underlying tumor predisposition condition should be considered for all types of brain tumors. The aim of this study was to report the dramatic history of a VHL Tunisian family with many affected adolescents presenting central nervous system hemangioblastomas among wich many died in their twenties and those who survived suffered from depression and suicide attempts. To provide optimal clinical care and genetic counseling to affected patients and their young relatives, we conducted a literature review to answer the major question for this family: are there any preventive approaches to escape tumor initiation in our at-risk relatives at young age? The onset of VHL syndrome at the index case of our Tunisian family was at the age of 40 years when she presented a blurred vision on the right, related to retinal angiomatosis. The evolution was caraterised by recurrent eye lesions, the development of multiple renal tumors and hemangioblastomas at the cerebral, cerebellar and cervical spinal cord levels with neurologic symptoms and various functional nervous sequels after neurosurgical resections. Familial features of VHL were present in half of her siblings (6 among 12). Her 2 adolescent sisters, dead at the age of 20, harbored cerebral hemangioblastomas, whereas 2 of her brothers who died respectively at the age of 21 and 47 years harbored respectively ocular angiomas and vertebral angiomas. A third 48 year-old alive brother harbored cerebral hemangioblastoma as well as renal cell carcinoma. Only preimplantation genetic diagnosis (PGD) to select unaffected embryos can be applied to prevent the disease. High-throughput methods such as microarrays and sequencing are available nowadays for late-onset disorders with genetic predispositions. Long term surveillance and timely preventive treatment of lesions are crucial for VHL disease carriers. Effective psychosocial support to vulnerable children and their families is also essential.

Polyunsaturated Fatty Acids in Mother, Infant, and Placental Tissue, and Their Relationship With Pre-Pregnancy BMI

ObjectivesMaternal obesity produces inflammation, which may result in adverse pregnancy outcomes such as preterm birth. Polyunsaturated fatty acids (PUFA), including omega-6 (n-6) and omega-3 (n-3) fatty acids, regulate inflammation and may mitigate the negative effects of inflammation. Previous studies report higher n-6 and lower n-3 PUFA concentration in early to mid-pregnancy for individuals with higher pre-pregnancy BMI (pBMI). However, the relationship between PUFA concentration at delivery and pBMI are not well understood. The purpose of this study is to determine the relationship between pBMI and maternal plasma, umbilical cord plasma, and placental PUFA concentrations, as well as PUFA intrauterine transfer percentage (IUTP).MethodsFollowing IRB approval, maternal plasma, umbilical cord plasma, and placental samples were collected at delivery from 55 maternal-infant dyads. IUTPs for each PUFA (linoleic acid (LA), α-linolenic acid (ALA), arachidonic acid (AA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA)) were calculated as [cord blood]/[maternal blood] × 100. Spearman's correlations assessed relationships between PUFA levels, PUFA IUTP, and pBMI. Linear regression models were adjusted for smoking status. A p-value < 0.05 was considered statistically significant.ResultsThe mean pBMI for our cohort was 28.7 kg/m2. Preceding pregnancy, 21% of mothers were normal or underweight, 36% overweight, and 43% obese. Maternal LA (R = −0.3, p = 0.03), maternal DHA (R = −0.27, p = 0.04), and placental EPA (R = −0.42, p = 0.02) were significantly correlated with maternal pBMI. After adjusting for smoking status, no correlations remained significant. PUFA cord levels and PUFA IUTP were not correlated to pBMI.ConclusionsTo our knowledge, this is the first study exploring relationships between pBMI and PUFA levels at delivery. Our findings contrast with previous research reporting correlations between PUFA levels and pBMI in early to mid-pregnancy. The effects of pBMI on PUFA status may be most prominent early in pregnancy. Future research should explore the relationship between pBMI and PUFA levels across all stages of pregnancy.Funding SourcesUNMC Pediatrics Department; Child Health Research Institute.

Knockdown of PAR2 alleviates cancer-induced bone pain by inhibiting the activation of astrocytes and the ERK pathway

ObjectiveCancer-induced bone pain (CIBP) is a kind of pain with complex pathophysiology. Proteinase-activated receptor 2 (PAR-2) is involved in CIBP. This study explored the effects of PAR-2 on CIBP rats.MethodsCIBP rat model was established by injecting Walker 256 rat breast cancer cells into the left tibia of female Sprague-Dawley rats and verified by tibial morphology observation, HE staining, and mechanical hyperalgesia assay. CIBP rats were injected with PAR-2 inhibitor, ERK activator, and CREB inhibitor through the spinal cord sheath on the 13th day after operation. CIBP behaviors were measured by mechanical hyperalgesia assay. On the 14th day after operation, L4-5 spinal cord tissues were obtained. PAR-2 expression, co-expression of PAR-2 and astrocyte marker GFAP, GFAP mRNA and protein levels and the ERK pathway-related protein levels were detected by Western blot, immunofluorescence double staining, RT-qPCR, and Western blot.ResultsCIBP rats had obvious mechanical hyperalgesia and thermal hyperalgesia from the 7th day after modeling; mechanical hyperalgesia threshold and thermal threshold were decreased; PAR-2 was increased in spinal cord tissues and was co-expressed with GFAP. PAR-2 silencing alleviated rat CIBP by inhibiting astrocyte activation. p-ERK/t-ERK and p-CREB/t-CREB levels in CIBP spinal cord were elevated, the ERK/CREB pathway was activated, while the ERK/CREB pathway was inhibited by PAR-2 silencing. The alleviating effect of PAR-2 inhibitor on hyperalgesia behaviors in CIBP rats were weakened by ERK activator, while were partially restored by CREB inhibitor.ConclusionsPAR-2 knockdown inhibited the ERK/CREB pathway activation and astrocyte activation, thus alleviating CIBP in rats.

Progressive multifocal leukoencephalopathy, more than an encephalopathy

Progressive multifocal leukoencephalopathy is a pathology associated with the presence of the JC virus, although it occurs in other conditions, nowadays most cases occur in patients with AIDS, in severe stages of immunosuppression. This condition, and hence its name, has always been associated with the presence of intracerebral lesions, where it can have a wide distribution. However, it is very rare, if ever, to report lesions of this disease in the spinal cord. We present a case of a 40-year-old patient, an HIV carrier in the AIDS stage, who, in addition to presenting brain lesions, had multiple lesions at the cervical spinal cord level. We believe that these lesions may be more common than believed and should be intentionally sought if possible.

Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit.

In perilous and stressful situations, the ability to suppress pain can be critical for survival. The rostral ventromedial medulla contains neurons that robustly inhibit nocioception at the level of the spinal cord through a top-down modulatory pathway. Although much is known about the role of the rostral ventromedial medulla in the inhibition of pain, the precise ability to directly manipulate pain-inhibitory neurons in the rostral ventromedial medulla has never been achieved. We now expose a cellular circuit that inhibits nocioception and itch in mice. Through a combination of molecular, tracing and behavioural approaches, we found that rostral ventromedial medulla neurons containing the kappa-opioid receptor inhibit itch and nocioception. With chemogenetic inhibition, we uncovered that these neurons are required for stress-induced analgesia. Using intersectional chemogenetic and pharmacological approaches, we determined that rostral ventromedial medulla kappa-opioid receptor neurons inhibit nocioception and itch through a descending circuit. Lastly, we identified a dynorphinergic pathway arising from the periaqueductal grey that modulates nociception within the rostral ventromedial medulla. These discoveries highlight a distinct population of rostral ventromedial medulla neurons capable of broadly and robustly inhibiting itch and nocioception.

Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.

Perinatal pharmacology is influenced by a myriad of physiological variables that are changing dynamically. The influence of these covariates has not been assessed systemically. The objective of this work was to use theophylline as a model drug and to predict its pharmacokinetics before, during (including prediction of the umbilical cord level), and after pregnancy as well as in milk (after single and multiple doses) and in neonates using a physiological-based pharmacokinetic (PBPK) model. Neonatal theophylline exposure from milk consumption was projected in both normal term and preterm subjects. Predicted infant daily doses were calculated using theophylline average and maximum concentration in the milk as well as an estimate of milk consumption. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted theophylline concentrations in non-pregnant and pregnant populations at different gestational weeks were within 2-fold of the observations and the observed concentrations fell within the 5th−95th prediction interval from the PBPK simulations. The PBPK model predicted an average cord-to-maternal plasma ratio of 1.0, which also agrees well with experimental observations. Predicted postpartum theophylline concentration profiles in milk were also in good agreement with observations with a predicted milk-to-plasma ratio of 0.68. For an infant of 2 kg consuming 150 ml of milk per day, the lactation model predicted a relative infant dose (RID) of 12 and 17% using predicted average (Cavg,ss) and maximum (Cmax,ss) concentration in milk at steady state. The maximum RID of 17% corresponds to an absolute infant daily dose of 1.4 ± 0.5 mg/kg/day. This dose, when administered as 0.233 mg/kg every 4 h, to resemble breastfeeding frequency, resulted in plasma concentrations as high as 3.9 (1.9–6.8) mg/L and 2.8 (1.3–5.3) (5th−95th percentiles) on day 7 in preterm (32 GW) and full-term neonatal populations.

Risk factors and prognosis of spinal cord injury without radiological abnormality in children in China.

BackgroundCompared to adults, spinal cord injury without radiographic abnormality (SCIWORA) is more common in children due to the congenital spinal soft tissue elasticity and immature vertebral bodies. In this study, we aimed to investigate the risk factors and prognosis associated with SCIWORA in China.MethodWe retrospectively examined patient records at the First Hospital of Jilin University from January 2007 to December 2020. Patients diagnosed with SCIWORA were included in the study group (n=16). The age, gender, history of trauma, symptoms, injury level of the spinal cord, the American Spinal Injury Association (ASIA) impairment score according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), as well as laboratory and imaging findings were analyzed.ResultThe study group included 16 patients with SCIWORA with a mean age of 6.69±2.51 y. The ISNCSCI impairment scale was significantly different between the pre-school age patients (≤7 years old) and school age patients (>7 years old) before (P=0.044) and after therapy (P=0.002). Similarly, magnetic resonance imaging demonstrated a significant difference in the spinal injury level between pre-school age and school age patients (P=0.041). Further, the study group was subdivided into three subgroups according to the cause of trauma: Dance, Taekwondo, or Falls. Magnetic resonance imaging revealed significant differences among the three subgroups (P=0.041).ConclusionCompared to school-age patients, pre-school-age patients were more vulnerable to SCIWORA with more severe ISNCSCI scores. Dance and Taekwondo are among the risk factors associated with SCIWORA in Chinese children.

Extremely low frequency magnetic exposure attenuates oxidative stress and apoptotic cell death in injured spinal cord of rats

Secondary spinal cord injury (SCI) sets on immediately after trauma which results in vascular, morphological and biochemical changes at the site of lesion. Amongst these, the crucial events such as oxidative stress and apoptosis result in spreading the injury to adjacent tissues following the initial insult. Exposure to extremely low frequency magnetic field (ELFMF) is reported to modulate oxidative stress and cell death in vivo. Here, we investigated the influence of ELFMF on oxidative stress and cell death after SCI. Adult male Wistar rats were divided into Sham-SCI (Laminectomy only), Sham-SCI+MF (ELFMF exposure; 17.96 μT intensity, 50 Hz frequency, 2 h duration/day to Sham-SCI rats), SCI (complete transection of T13 spinal cord) and SCI+MF (ELFMF exposure to SCI rats) groups. They were sacrificed on day 2 for antioxidant assay and day 1, 2 and 3 for cell death study. The oxidative stress was assessed by antioxidant enzyme activities and the cell death was assessed by TUNEL assay and Caspase-3 immnuohistochemistry. Data revealed significant reduction in the lipid peroxidation and number of cells undergone cell death besides improvement in antioxidant levels in the spinal cord of ELFMF exposed SCI rats. These novel findings demonstrate the potential of ELFMF to attenuate oxidative stress and cell death in the early stage of secondary injury process after SCI.

Probing the Cellular Basis of Spinal Kappa Opioid Receptor Inhibition of Itch

The kappa opioid receptor (KOR, encoded by Oprk1) is an extremely attractive target for the treatment of chronic itch. The KOR agonist nalfurafine is used to treat chronic itch associated with kidney and liver disease in Japan, with additional KOR agonists in development for atopic dermatitis and neuropathic itch. Despite the clinical promise of KOR agonists, the cellular basis of KOR inhibition of itch remains unknown. Previous work from our lab demonstrated that KOR inhibition of itch occurs – at least in part – at the level of the spinal cord, raising the question: how does KOR signaling inhibit itch spinal circuits? We are addressing this fundamental gap in knowledge through a combination of molecular, genetic, behavioral, and physiological approaches in mice. First, we used fluorescent in situ hybridization to determine which spinal neuron populations express Oprk1. We show that Oprk1 is expressed within a heterogenous population of spinal neurons, but primarily those that express the neuropeptide substance P or the neurokinin-1 receptor, which drive itch behavior. Moreover, retrograde viral labeling revealed that Oprk1 is expressed in spinoparabrachial neurons that relay itch input from the spinal cord to the brain. Next, we tested whether Oprk1 spinal neurons contribute to itch behaviors. We selectively expressed excitatory chemogenetic tools in Oprk1-Cre spinal neurons and found that chemogenetic activation of these neurons potentiated itch behaviors. Finally, we used ex vivo two-photon calcium imaging of the spinal cord to visualize the neuron networks activated by spinal itch neuropeptides and investigated how KOR agonists inhibit these networks. Notably, these data are the first in-depth look into the cellular basis of spinal KOR inhibition of itch and provide fundamental mechanistic insights into KOR agonists that are clinically effective in alleviating chronic itch. Supported by NIH grants F32NS110155 (TDS) and R01NS0967905 (SER).

Pulse corticosteroids for the management of extensive CNS tuberculosis presenting with acute-onset quadriparesis.

Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy.

Caloric Restriction Alleviates CFA-Induced Inflammatory Pain via Elevating β-Hydroxybutyric Acid Expression and Restoring Autophagic Flux in the Spinal Cord.

Inflammatory pain is the most common type of pain encountered in clinical practice; however, the currently available treatments are limited by insufficient efficacy and side effects. Therefore, new methods to relieve inflammatory pain targeting new mechanisms are urgently needed. Preclinical investigations have shown that CR (calorie restriction) exerts analgesic effects in neuropathic and cancer pain; however, the effect of CR on chronic inflammatory pain remains unknown. During calorie restriction, autophagy, a lysosome-dependent degradation process, can be activated to support cell survival. In the present study, we investigated the analgesic effects of CR on complete Freund’s adjuvant (CFA)-induced inflammatory pain. The accumulation of LC3-II and p62 showed impaired autophagic flux in the ipsilateral spinal cord of mice with CFA-induced inflammatory pain. CR alleviated mechanical allodynia and thermal hyperalgesia and reduced paw edema and pro-inflammatory factors following CFA administration. CR exerted an analgesic effect by restoring autophagic flux in the spinal cord. Regarding the mechanisms underlying the analgesic effects of CR, β-hydroxybutyric acid (BHB) was studied. CR increased BHB levels in the ipsilateral spinal cord. Furthermore, exogenous BHB administration exerted an analgesic effect by restoring autophagic flux in the spinal cords of CFA-induced inflammatory pain mice. Taken together, these results illustrated that CR relieved inflammatory pain by restoring autophagic flux in the spinal cord, while BHB controlled the benefits of CR, suggesting that CR or BHB might be a promising treatment for inflammatory pain.

Emerging role of neuregulin-1beta1 in pathogenesis and progression of multiple sclerosis

Emerging role of neuregulin-1beta1 in pathogenesis and progression of multiple sclerosis

TRANSVERSE MYELITIS DUE TO TUBERCULOSIS: CASE REPORT WITH NARRATIVE REVIEW

Tuberculosis is a global public health problem, which continues to increase morbidity and mortality around the world. The infectious agent is the well-known Koch bacillus, Mycobacterium tuberculosis complex, discovered in 1882 by Robert Koch. Tuberculosis in the central nervous system with spinal cord involvement is a rare event. It is believed that the medullar infection is due to the contiguity of a bone infection at the vertebral level. The initial symptoms of spinal cord infection are due to the motor and sensory compromise of the compromised spinal cord level. Infection in the central nervous system occurs mainly due to the presentation of meningitis and intramedullary tuberculosis in HIV-positive patients, which is considered to represent only 2% of the cases of tuberculosis of the central nervous system. We present a case of spinal cord involvement due to tuberculosis.

The T-Type Calcium Channel Cav3.2 in Somatostatin Interneurons in Spinal Dorsal Horn Participates in Mechanosensation and Mechanical Allodynia in Mice.

Somatostatin-positive (SOM+) neurons have been proposed as one of the key populations of excitatory interneurons in the spinal dorsal horn involved in mechanical pain. However, the molecular mechanism for their role in pain modulation remains unknown. Here, we showed that the T-type calcium channel Cav3.2 was highly expressed in spinal SOM+ interneurons. Colocalization of Cacna1h (which codes for Cav3.2) and SOMtdTomato was observed in the in situ hybridization studies. Fluorescence-activated cell sorting of SOMtdTomato cells in spinal dorsal horn also proved a high expression of Cacna1h in SOM+ neurons. Behaviorally, virus-mediated knockdown of Cacna1h in spinal SOM+ neurons reduced the sensitivity to light touch and responsiveness to noxious mechanical stimuli in naïve mice. Furthermore, knockdown of Cacna1h in spinal SOM+ neurons attenuated thermal hyperalgesia and dynamic allodynia in the complete Freund’s adjuvant-induced inflammatory pain model, and reduced both dynamic and static allodynia in a neuropathic pain model of spared nerve injury. Mechanistically, a decrease in the percentage of neurons with Aβ-eEPSCs and Aβ-eAPs in superficial dorsal horn was observed after Cacna1h knockdown in spinal SOM+ neurons. Altogether, our results proved a crucial role of Cav3.2 in spinal SOM+ neurons in mechanosensation under basal conditions and in mechanical allodynia under pathological pain conditions. This work reveals a molecular basis for SOM+ neurons in transmitting mechanical pain and shows a functional role of Cav3.2 in tactile and pain processing at the level of spinal cord in addition to its well-established peripheral role.