Spinothalamic Research Articles

Lesions to both somatic and affective pain pathways lead to decreased salience network connectivity.

Human pain is a salient stimulus composed of two main components: a sensory/somatic component, carrying peripheral nociceptive sensation via the spinothalamic tract and brainstem nuclei to the thalamus and then to sensory cortical regions, and an affective (suffering) component, where information from central thalamic nuclei is carried to the anterior insula, dorsal anterior cingulate cortex and other regions. While the sensory component processes information about stimulus location and intensity, the affective component processes information regarding pain-related expectations, motivation to reduce pain and pain unpleasantness. Unlike investigations of acute pain that are based on the introduction of real-time stimulus during brain recordings, chronic pain investigations are usually based on longitudinal and case-control studies, which are limited in their ability to infer the functional network topology of chronic pain. In the current study, we utilized the unique opportunity to target the CNS's pain pathways in two different hierarchical locations to establish causality between pain relief and specific connectivity changes seen within the salience and sensorimotor networks. We examined how lesions to the affective and somatic pain pathways affect resting-state network topology in cancer patients suffering from severe intractable pain. Two procedures have been employed: percutaneous cervical cordotomy (n = 15), hypothesized to disrupt the transmission of the sensory component of pain along the spinothalamic tract, or stereotactic cingulotomy (n = 7), which refers to bilateral intracranial ablation of an area in the dorsal anterior cingulate cortex and is known to ameliorate the affective component of pain. Both procedures led to immediate significant alleviation of experienced pain and decreased functional connectivity within the salience network. However, only the sensory procedure (cordotomy) led to decreased connectivity within the sensorimotor network. Thus, our results support the existence of two converging systems relaying experienced pain, showing that pain-related suffering can be either directly influenced by interfering with the affective pathway or indirectly influenced by interfering with the ascending spinothalamic tract.

Pain Management and Rehabilitation for Central Sensitization in Temporomandibular Disorders: A Comprehensive Review.

Temporomandibular disorders (TMD) are a group of musculoskeletal diseases affecting masticatory muscles and temporomandibular joints (TMJ). In this context, the chronic TMD could be considered as a condition with chronic primary orofacial pain, presenting as myofascial TMD pain or TMJ arthralgia. In this context, myogenous TMD may present overlapping features with other disorders, such as fibromyalgia and primary headaches, characterized by chronic primary pain related to dysfunction of the central nervous system (CNS), probably through the central sensitization. This phenomenon could be defined as an amplified response of the CNS to sensory stimuli and peripheral nociceptive, characterized by hyperexcitability in the dorsal horn neurons in the spinal cord, which ascend through the spinothalamic tract. The main objectives of the management of TMD patients are: decreasing pain, increasing TMJ function, and reducing the reflex masticatory muscle spasm/pain. The first-line treatments are physical therapy, pharmacological drugs, occlusal splints, laser therapy, extracorporeal shockwave therapy, transcutaneous electrical nerve stimulation, and oxygen–ozone therapy. Although all these therapeutic approaches were shown to have a positive impact on the central sensitization of TMD pain, there is still no agreement on this topic in the scientific literature. Thus, in this comprehensive review, we aimed at evaluating the evidence on pain management and rehabilitation for the central sensitization in TMD patients.

Fibromyalgia-associated hyperalgesia is related to psychopathological alterations but not to gut microbiome changes.

Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. Our research team examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) and psychological disturbances are accompanied by alterations of the fecal microbiome. We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed through questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain. QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients. FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors, we conclude that the contribution of the gut microbiome to the pathophysiology of FMS is limited.

Utility of Diffusion and Magnetization Transfer MRI in Cervical Spondylotic Myelopathy: A Pilot Study.

Diffusion tensor imaging (DTI) and magnetization transfer (MT) magnetic resonance imaging (MRI) can help detect spinal cord pathology, and tract-specific analysis of their parameters, such as fractional anisotropy (FA), mean diffusivity, axial diffusivity (AD), radial diffusivity (RD) and MT ratio (MTR), can give microstructural information. We performed the tract-based acquisition of MR parameters of three major motor tracts: the lateral corticospinal (CS), rubrospinal (RuS) tract, and lateral reticulospinal (RS) tract as well as two major sensory tracts, i.e., the fasciculus cuneatus (FC) and spinal lemniscus, to detect pathologic change and find correlations with clinical items. MR parameters were extracted for each tract at three levels: the most compressed lesion level and above and below the lesion. We compared the MR parameters of eight cervical spondylotic myelopathy patients and 12 normal controls and analyzed the correlation between clinical evaluation items and MR parameters in patients. RuS and lateral RS showed worse DTI parameters at the lesion level in patients compared to the controls. Worse DTI parameters in those tracts were correlated with weaker power grasp at the lesion level. FC and lateral CS showed a correlation between higher RD and lower FA and MTR with a weaker lateral pinch below the lesion level.

Somatotopy of Mouse Spinothalamic Innervation and the Localization of a Noxious Stimulus Requires Deleted in Colorectal Carcinoma Expression by Phox2a Neurons.

Anterolateral system (AS) neurons transmit pain signals from the spinal cord to the brain. Their morphology, anatomy, and physiological properties have been extensively characterized and suggest that specific AS neurons and their brain targets are concerned with the discriminatory aspects of noxious stimuli, such as their location or intensity, and their motivational/emotive dimension. Among the recently unraveled molecular markers of AS neurons is the developmentally expressed transcription factor Phox2a, providing us with the opportunity to selectively disrupt the embryonic wiring of AS neurons to gain insights into the logic of their adult function. As mice with a spinal-cord-specific loss of the netrin-1 receptor deleted in colorectal carcinoma (DCC) have increased AS neuron innervation of ipsilateral brain targets and defective noxious stimulus localization or topognosis, we generated mice of either sex carrying a deletion of Dcc in Phox2a neurons. Such DccPhox2a mice displayed impaired topognosis along the rostrocaudal axis but with little effect on left-right discrimination and normal aversive responses. Anatomical tracing experiments in DccPhox2a mice revealed defective targeting of cervical and lumbar AS axons within the thalamus. Furthermore, genetic labeling of AS axons revealed their expression of DCC on their arrival in the brain, at a time when many of their target neurons are being born and express Ntn1 Our experiments suggest a postcommissural crossing function for netrin-1:DCC signaling during the formation of somatotopically ordered maps and are consistent with a discriminatory function of some of the Phox2a AS neurons.SIGNIFICANCE STATEMENT How nociceptive (pain) signals are relayed from the body to the brain remains an important question relevant to our understanding of the basic physiology of pain perception. Previous studies have demonstrated that the AS is a main effector of this function. It is composed of AS neurons located in the spinal cord that receive signals from nociceptive sensory neurons that detect noxious stimuli. In this study, we generate a genetic miswiring of mouse AS neurons that results in a decreased ability to perceive the location of a painful stimulus. The precise nature of this defect sheds light on the function of different kinds of AS neurons and how pain information may be organized.

Amygdala and anterior insula control the passage from nociception to pain.

Activation of the spinothalamic system does not always result in a subjective pain perception. While the cerebral network processing nociception is relatively well known, the one underlying its transition to conscious pain remains poorly described. We used intracranial electroencephalography in epileptic patients to investigate whether the amplitudes and functional connectivity of posterior and anterior insulae (PI and AI) and amygdala differ according to the subjective reports to laser stimuli delivered at a constant intensity set at nociceptive threshold. Despite the constant intensity of stimuli, all patients reported variable subjective perceptions from one stimulus to the other. Responses in the sensory PI remained stable throughout the experiment, hence reflecting accurately the stability of the stimulus. In contrast, both AI and amygdala responses showed significant enhancements associated with painful relative to nonpainful reports, in a time window corresponding to the conscious integration of the stimulus. Functional connectivity in the gamma band between these two regions increased significantly, both before and after stimuli perceived as painful. While the PI appears to transmit faithfully the actual stimulus intensity received via the spinothalamic tract, the AI and the amygdala appear to play a major role in the transformation of nociceptive signals into a painful perception.

Secondary damage and neuroinflammation in the spinal dorsal horn mediate post-thalamic hemorrhagic stroke pain hypersensitivity: SDF1-CXCR4 signaling mediation.

Central post-stroke pain (CPSP) is an intractable neuropathic pain, which can be caused by primary lesion of central somatosensory system. It is also a common sequelae of the thalamic hemorrhagic stroke (THS). So far, the underlying mechanisms of CPSP remain largely unknown. Our previous studies have demonstrated that SDF1-CXCR4 signaling in the hemorrhagic region contributes to the maintenance of the THS pain hypersensitivity via mediation of the thalamic neuroinflammation. But whether the spinal dorsal horn, an initial point of spinothalamic tract (STT), suffers from retrograde axonal degeneration from the THS region is still unknown. In this study, neuronal degeneration and loss in the spinal dorsal horn were detected 7 days after the THS caused by intra-thalamic collagenase (ITC) injection by immunohistochemistry, TUNEL staining, electron microscopy, and extracellular multi-electrode array (MEA) recordings, suggesting the occurrence of secondary apoptosis and death of the STT projecting neuronal cell bodies following primary THS via retrograde axonal degeneration. This retrograde degeneration was accompanied by secondary neuroinflammation characterized by an activation of microglial and astrocytic cells and upregulation of SDF1-CXCR4 signaling in the spinal dorsal horn. As a consequence, central sensitization was detected by extracellular MEA recordings of the spinal dorsal horn neurons, characterized by hyperexcitability of both wide dynamic range and nociceptive specific neurons to suprathreshold mechanical stimuli. Finally, it was shown that suppression of spinal neuroinflammation by intrathecal administration of inhibitors of microglia (minocycline) and astrocytes (fluorocitrate) and antagonist of CXCR4 (AMD3100) could block the increase in expression levels of Iba-1, GFAP, SDF1, and CXCR4 proteins in the dorsal spinal cord and ameliorate the THS-induced bilateral mechanical pain hypersensitivity, implicating that, besides the primary damage at the thalamus, spinal secondary damage and neuroinflammation also play the important roles in maintaining the central post-THS pain hypersensitivity. In conclusion, secondary neuronal death and neuroinflammation in the spinal dorsal horn can be induced by primary thalamic neural damage via retrograde axonal degeneration process. SDF1-CXCR4 signaling is involved in the mediation of secondary spinal neuroinflammation and THS pain hypersensitivity. This finding would provide a new therapeutic target for treatment of CPSP at the spinal level.

Distinct neural networks derived from galanin-containing nociceptors and neurotensin-expressing pruriceptors

Pain and itch are distinct sensations arousing evasion and compulsive desire for scratching, respectively. It's unclear whether they could invoke different neural networks in the brain. Here, we use the type 1 herpes simplex virus H129 strain to trace the neural networks derived from two types of dorsal root ganglia (DRG) neurons: one kind of polymodal nociceptors containing galanin (Gal) and one type of pruriceptors expressing neurotensin (Nts). The DRG microinjection and immunosuppression were performed in transgenic mice to achieve a successful tracing from specific types of DRG neurons to the primary sensory cortex. About one-third of nuclei in the brain were labeled. More than half of them were differentially labeled in two networks. For the ascending pathways, the spinothalamic tract was absent in the network derived from Nts-expressing pruriceptors, and the two networks shared the spinobulbar projections but occupied different subnuclei. As to the motor systems, more neurons in the primary motor cortex and red nucleus of the somatic motor system participated in the Gal-containing nociceptor-derived network, while more neurons in the nucleus of the solitary tract (NST) and the dorsal motor nucleus of vagus nerve (DMX) of the emotional motor system was found in the Nts-expressing pruriceptor-derived network. Functional validation of differentially labeled nuclei by c-Fos test and chemogenetic inhibition suggested the red nucleus in facilitating the response to noxious heat and the NST/DMX in regulating the histamine-induced scratching. Thus, we reveal the organization of neural networks in a DRG neuron type-dependent manner for processing pain and itch.

History of Spinal Cord "Pain" Pathways Including the Pathways Not Taken.

Traditional medical neuroanatomy/neurobiology textbooks teach that pain is generated by several ascending pathways that course in the anterolateral quadrant of the spinal cord, including the spinothalamic, spinoreticular and spinoparabrachial tracts. The textbooks also teach, building upon the mid-19th century report of Brown-Séquard, that unilateral cordotomy, namely section of the anterolateral quadrant, leads to contralateral loss of pain (and temperature). In many respects, however, this simple relationship has not held up. Most importantly, pain almost always returns after cordotomy, indicating that activation of these so-called “pain” pathways may be sufficient to generate pain, but they are not necessary. Indeed, Brown-Séquard, based on his own studies, eventually came to the same conclusion. But his new view of “pain” pathways was largely ignored, and certainly did not forestall Spiller and Martin's 1912 introduction of cordotomy to treat patients. This manuscript reviews the history of “pain” pathways that followed from the first description of the Brown-Séquard Syndrome and concludes with a discussion of multisynaptic spinal cord ascending circuits. The latter, in addition to the traditional oligosynaptic “pain” pathways, may be critical to the transmission of “pain” messages, not only in the intact spinal cord but also particularly after injury.

Characterisation of deep dorsal horn projection neurons in the spinal cord of the Phox2a::Cre mouse line.

Projection neurons belonging to the anterolateral system (ALS) underlie the perception of pain, skin temperature and itch. Many ALS cells are located in laminae III-V of the dorsal horn and the adjacent lateral white matter. However, relatively little is known about the excitatory synaptic input to these deep ALS cells, and therefore about their engagement with the neuronal circuitry of the region. We have used a recently developed mouse line, Phox2a::Cre, to investigate a population of deep dorsal horn ALS neurons known as “antenna cells”, which are characterised by dense innervation from peptidergic nociceptors, and to compare these with other ALS cells in the deep dorsal horn and lateral white matter. We show that these two classes differ, both in the density of excitatory synapses, and in the source of input at these synapses. Peptidergic nociceptors account for around two-thirds of the excitatory synapses on the antenna cells, but for only a small proportion of the input to the non-antenna cells. Conversely, boutons with high levels of VGLUT2, which are likely to originate mainly from glutamatergic spinal neurons, account for only ∼5% of the excitatory synapses on antenna cells, but for a much larger proportion of the input to the non-antenna cells. VGLUT1 is expressed by myelinated low-threshold mechanoreceptors and corticospinal axons, and these innervate both antenna and non-antenna cells. However, the density of VGLUT1 input to the non-antenna cells is highly variable, consistent with the view that these neurons are functionally heterogeneous.

Spinal cord involvement in MOGAD, AQP4-Ab NMOSD & MS

IntroductionSpinal cord involvement is important in aquaporin-4(AQP4) antibody(Ab)-positive neuro- myelitis optica spectrum disorder(NMOSD), myelin-oligodendrocyte glycoprotein-Ab disease(MOGAD) and multiple sclerosis(MS).MethodsData from adults with spinal cord involvement and MOGAD(n=46) or AQP4-Ab(n=69) were retrospectively analysed. An additional c-spine MRI (3DT1,3DT2,2D axial T2*,DTI,MTR) was performed and analysed using SCT and FSL on 20 patients from each cohort, together with 20 MS and 20 healthy volunteers(HV).ResultsCompared to AQP4-Ab, MOGAD patients had more short lesions(p≤0.0001) and multiple lesions(p≤0.001). In AQP4-Ab, age was the most important factor affecting long-term outcome; while in MOGAD it was the presence of a brainstem lesion at the time of the myelitis. In the cervical cord MRI study, the MOGAD group had no residual lesions, and did not show a significant reduction in either CSA, FA or MTR, but showed a reduction of grey matter volume in those with cervical cord involvement(p=0.0229). The AQP4-Ab group showed a significantly reduced CSA(p=0.0288) and FA(p=0.0085) and a reduced MTR compared to both HV(p≤0.0001) and MOGAD(p=0.0096). This was driven by those with cervical cord lesions. The MS group had a significantly reduced FA(p=0.0204), GM(p=0.0133) and MTR(p=0.0106). FA associated with EDSS(p=0.02,R2=0.25) in the corticospinal tract and pain in the spinothalamic tract(p≤0.01,R2=0.32). Overall, CSA was the strongest predictor of EDSS.ConclusionMOGAD may predominantly affect the grey matter. AQP4-Ab disease shows the most severe, localised cord damage. MRI metrics do not discriminate these conditions but show clinical significance.romina.mariano@ndcn.ox.ac.uk

The Role of Mediodorsal Thalamic Projections to Prelimbic Medial Prefrontal Cortex in Affective Pain Processing and Pain Tolerance

Both human and rodent studies demonstrate that the mediodorsal (MD) thalamus, a target of spinothalamic tract neurons, is involved in processing the affective component of pain. The specific role of MD nuclei and their projections in pain remains incompletely understood. MD projects to several cortical regions, one of which is the prelimbic region of the prefrontal cortex (PL), an area thought to play a role in pain processing and modulation. The purpose of this study was to elucidate the role of MD neurons that project to the PL in affective pain processing and pain tolerance. We utilized viral vectors and the Cre-lox system to specifically express designer receptors exclusively activated by designer drugs (DREADDs) in MD pyramidal neurons that project to the PL to activate or deactivate the circuit with CNO. Mice received chronic constriction injuries (CCI) contralateral to viral injections. This was followed by conditioned place aversion (CPA) or preference tests and the operant plantar thermal assay (OPTA). Activating the unilateral MD-PL circuit using excitatory DREADDs in naïve mice did not produce a conditioned place aversion. It did, however, produce place aversion in mice with CCI. Unilaterally inhibiting the MD-PL circuit in mice with CCI did not produce a place preference. There was no difference in the time spent tolerating a noxious temperature to receive a sucrose reward when this circuit was either activated or inhibited in mice with CCI. The MD-PL circuit is involved in the enhancement of aversion in mice with chronic pain. This circuit, however, is not sufficient to produce aversion in pain-free mice. This circuit may not be necessary for the affective component of pain, as unilaterally inhibiting it did not result in preference in mice with CCI. Finally, this circuit may not be involved with the modulation of pain tolerance in mice with CCI. Grant support from R01 NS107356.

Mapping thalamic-anterior cingulate monosynaptic inputs in adult mice.

The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.

Anterior Spinal Cord Ischemia due to an Acute Aortic Intramural Type B Hematoma

Anterior Spinal Cord Ischemia due to an Acute Aortic Intramural Type B Hematoma

Affective function of touch and the neurophysiological mechanism

<p id="p00005">Touch is an important sensory channel for individuals to explore the external world in everyday life. The sense of touch helps us to discriminate the location of a stimulus on the skin surface, to identify the shape, size and texture of objects. However, touch can also be affective. The motivational-affective dimension of touch is involved in coding its valence and motivational relevance. This aspect of tactile sensation plays an important role in maintaining social bonding and promoting interpersonal communication. <p id="p00006">The affective function of interpersonal touch can be achieved through unimodal presentations or multimodal information integration processing. That is, tactile action itself, either a strong handshake or a tender hug, can directly convey emotions. Although the accuracy of decoding six basic emotions (anger, fear, happiness, sadness, disgust, and surprise) from interpersonal touch are slightly less than from the facial expression and vocal information, interpersonal touch has advantages in conveying social emotions such as "love", "gratitude" and "sympathy". Such advantages reflect the important significance of affective touch in establishing social bonding and promoting cooperative relationships. Further more, the affective meaning and social attributes carried by interpersonal touch can provide social background for emotion of other modal （e.g., visual or auditory） information processing, so as to enhance participants’ attention and to sharpen their social evaluation of emotional cues. <p id="p00007">Compared with sensory-discriminative subsystem, the motivational-affective subsystem has a special neurophysiological mechanism. For example, C-tactile (CT) afferents are strongly implicated as the neurobiological substrate underlying the affective property of touch. CTs, a class of slowly conducting mechanoreceptors, are specially tuned to the properties of human physical contact. They fire maximally to skin-temperature, light-pressure stroking at a rate of 1-10 cm per s. C-tactile-mediated affective tactile stimulation project in spinothalamic tract (STT) pathway (the spinal signaling of orofacial C-fiber mediated affective touch is still unclear), bypass the primary somatosensory cortex, directly project to the insular cortex, and then process in the amygdala, medial prefrontal cortex (mPFC), posterior superior temporal sulcus (pSTS) and other core areas of the “social brain” neural network. In addition, evidence from EEG research shows that, beta oscillation at parietal scalp sites, may be related to the affective representation of tactile stimuli, and theta oscillation at frontal, parietal, temporal, occipital scalp sites, may reflect an attentional-emotional regulatory mechanism of affective touch. <p id="p00008">Another complex facet of touch is that, affective touch would be complicated by its inextricable links to context, gender and sexuality, culture, and other individual, interpersonal, and societal factors. Moreover, learned from the previous research on facial emotion perception, a considerable body of work about affective touch are also around the topic of coding-decoding of basic emotions, so that the results fail to fully reveal the specificity of tactile channel in transmitting social emotions. Therefore, we should pay more attention to top-down contextual factors in the future researches, such as personal relationship, cultural difference, and social context, that may influence how to define and interpret the emotion and motivation of interpersonal touch. Meanwhile, although the time course of emotional touch perception was explored with electrophysiological measures, however no clear index has been identified till now. In addition, in order to reveal the relevance and independence between the sensory-discriminative and motivational-affective subsystems, such as activation likelihood estimate (ALE) meta-analysis and meta-analytic connectivity modeling (MACM) analysis can be used to reveal the cortical functional neuroanatomy supporting a distinction between affective and discriminative touch.

Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing

To further advance functional MRI (fMRI)-based brain science, it is critical to dissect fMRI activity at the circuit level. To achieve this goal, we combined brain-wide fMRI with neuronal silencing in well-defined regions. Since focal inactivation suppresses excitatory output to downstream pathways, intact input and suppressed output circuits can be separated. Highly specific cerebral blood volume-weighted fMRI was performed with optogenetic stimulation of local GABAergic neurons in mouse somatosensory regions. Brain-wide spontaneous somatosensory networks were found mostly in ipsilateral cortical and subcortical areas, which differed from the bilateral homotopic connections commonly observed in resting-state fMRI data. The evoked fMRI responses to somatosensory stimulation in regions of the somatosensory network were successfully dissected, allowing the relative contributions of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC) inputs, and local intracortical circuits to be determined. The ventral posterior thalamic nucleus receives ST inputs, while the posterior medial thalamic nucleus receives CT inputs from the primary somatosensory cortex (S1) with TC inputs. The secondary somatosensory cortex (S2) receives mostly direct CC inputs from S1 and a few TC inputs from the ventral posterolateral nucleus. The TC and CC input layers in cortical regions were identified by laminar-specific fMRI responses with a full width at half maximum of <150 µm. Long-range synaptic inputs in cortical areas were amplified approximately twofold by local intracortical circuits, which is consistent with electrophysiological recordings. Overall, whole-brain fMRI with optogenetic inactivation revealed brain-wide, population-based, long-range circuits, which could complement data typically collected in conventional microscopic functional circuit studies.

Diagnostic sensitivity of traumatic axonal injury of the spinothalamic tract in patients with mild traumatic brain injury.

Diffusion tensor tractography (DTT) can detect traumatic axonal injury (TAI) in patients whose conventional brain magnetic resonance imaging results are negative. This study investigated the diagnostic sensitivity of TAI of the spinothalamic tract (STT) in patients with a mild traumatic brain injury (TBI) suffering from central pain symptoms, using DTT.Thirty-five patients with central pain following mild TBI and 30 healthy control subjects were recruited for this study. After DTT-based reconstruction of the STT, we analyzed the STT in terms of configuration (narrowing and/or tearing) and the DTT parameters (fractional anisotropy and tract volume).Thirty-three (94.3%) patients had at least 1 DTT parameter value at 1 standard deviation below the control group value, and 20 (57.1%) patients had values at 2 standard deviations, below the control group value. All 35 patients showed STT abnormalities (tearing, narrowing, or both) on DTT.A high diagnostic sensitivity of TAI of the STT in patients with mild TBI was achieved. However, the small number of subjects who visited the university hospital and the limitations of DTT should be considered when generalizing the results of this study.

Central Nervous System Tumors in Children.

Central Nervous System Tumors in Children.

The behavioral and molecular effects of estradiol and progesterone on a rat model of spinothalamic tract lesion

The behavioral and molecular effects of estradiol and progesterone on a rat model of spinothalamic tract lesion

Microglial deactivation by adeno-associated virus expressing small-hairpin GCH1 has protective effects against neuropathic pain development in a spinothalamic tract-lesion model.

AimsNeuropathic pain after spinal cord injury is one of the most difficult clinical problems after the loss of mobility, and pharmacological or neuromodulation therapy showed limited efficacy. In this study, we examine the possibility of pain modulation by a recombinant adeno‐associated virus (rAAV) encoding small‐hairpin RNA against GCH1 (rAAV‐shGCH1) in a spinal cord injury model in which neuropathic pain was induced by a spinothalamic tract (STT) lesion.MethodsMicro‐electric lesioning was used to damage the left STT in rats (n = 32), and either rAAV‐shGCH1 (n = 19) or rAAV control (n = 6) was injected into the dorsal horn of the rats at the same time. On postoperative days 3, 7, and 14, we evaluated neuropathic pain using a behavioral test and microglial activation by immunohistochemical staining.ResultsA pain modulation effect of shGCH1 was observed from postoperative days 3 to 14. The mechanical withdrawal threshold was 13.0 ± 0.95 in the shGCH1 group, 4.3 ± 1.37 in the control group, and 3.49 ± 0.85 in sham on postoperative day 3 (p < 0.0001) and continued to postoperative day 14 (shGCH1 vs. control: 11.4 ± 1.1 vs. 2.05 ± 0.60, p < 0.001 and shGCH1 vs. sham: 11.4 ± 1.1 vs. 1.43 ± 0.54, p < 0.001). Immunohistochemical staining of the spinal cord dorsal horn showed deactivation of microglia in the shGCH1 group without any change of delayed pattern of astrocyte activation as in STT model.ConclusionsNeuropathic pain after spinal cord injury can be modulated bilaterally by deactivating microglial activation after a unilateral injection of rAAV‐shGCH1 into the dorsal horn of a STT lesion spinal cord pain model. This new attempt would be another therapeutic approach for NP after SCI, which once happens; there is no clear curative options still now.