Functional organization and connectivity of the dorsal column nuclei complex reveals a sensorimotor integration and distribution hub.

The dorsal column nuclei complex (DCN-complex) includes the dorsal column nuclei (DCN, referring to the gracile and cuneate nuclei collectively), external cuneate, X, and Z nuclei, and the median accessory nucleus. The DCN are organized by both somatotopy and modality, and have a diverse range of afferent inputs and projection targets. The functional organization and connectivity of the DCN implicate them in a variety of sensorimotor functions, beyond their commonly accepted role in processing and transmitting somatosensory information to the thalamus, yet this is largely underappreciated in the literature. To consolidate insights into their sensorimotor functions, this review examines the morphology, organization, and connectivity of the DCN and their associated nuclei. First, we briefly discuss the receptors, afferent fibers, and pathways involved in conveying tactile and proprioceptive information to the DCN. Next, we review the modality and somatotopic arrangements of the remaining constituents of the DCN-complex. Finally, we examine and discuss the functional implications of the myriad of DCN-complex projection targets throughout the diencephalon, midbrain, and hindbrain, in addition to their modulatory inputs from the cortex. The organization and connectivity of the DCN-complex suggest that these nuclei should be considered a complex integration and distribution hub for sensorimotor information.

Normal tolerance limits for side-to-side differences in diameters of major lower limbs arteries of 228 healthy subjects.

PURPOSE: To determine reference values and tolerance limits of between-side differences for the calibers of the common femoral artery (CFA), superficial femoral artery (SFA), popliteal artery (PA), dorsalis pedis artery (DPA), and posterior tibial artery (PTA). MATERIALS AND METHODS: Calibers of arteries, defined as the largest distance between internal hyperechogenic lines of the intima-media complex of the arterial wall, were measured during the diastole phase determined from echo-tracking B mode ultrasound scanning and grey-scale ultrasound in 228 healthy volunteers aged 18-81 years (43.1 ± 16.7). RESULTS: The mean, 95% confidence and tolerance limits covering 90% of population for left and right side of each artery were: CFA: 8.1 mm, 7.9-8.3 mm, 6.0-10.3 mm; 8.1 mm, 7.9-8.5 mm, 5.9-10.2 mm; SFA: 6.2 mm, 6.0-6.3 mm, 4.7-7.6 mm; 6.1 mm, 6.0-6.3 mm, 4.7-7.6 mm; PA: 6.1 mm, 6.0-6.2 mm, 4.6-7.6 mm; 6.1 mm, 5.9-6.2 mm, 4.5-7.6 mm; DPA: 2.0 mm, 1.9-2.0 mm, 1.2-2.7 mm; 2.0 mm, 1.9-2.0 mm, 1.2-2.8 mm; PTA: 2.1 mm, 2.0-2.1 mm, 1.4-2.8 mm; 2.1 mm, 2.1-2.2 mm, 1.4-2.8 mm, respectively. Tolerance limits for between-side differences and ratios were: CFA - 0.5-0.7 mm, 0.9-1.1; SFA - 0.5-0.6 mm, 0.9-1.1; PA - 0.5-0.5 mm, 0.9-1.1; DPA -0.4-0.4 mm, 0.8-1.2; PTA - 0.4-0.4 mm, 0.8-1.2. Regression analysis showed weight and age dependency of vessels diameters. There are no differences between men and woman in vessels size, except in DPA's, when body weight and age are taken into account in a regression analysis. CONCLUSIONS: We estimated normal reference tolerance limits of side-to-side differences in diameters of lower limb arteries. The limits can inform an investigator what differences in diameters occur in healthy individuals, and hence can serve as cut-offs in diagnostic and screening strategies.

Evoked Compound Action Potentials Reveal Spinal Cord Dorsal Column Neuroanatomy.

INTRODUCTION: The electrically evoked compound action potential (ECAP) is a measure of the response from a population of fibers to an electrical stimulus. ECAPs can be assessed during spinal cord stimulation (SCS) to elucidate the relationship between stimulation, electrophysiological response, and neuromodulation. This has consequences for the design and programming of SCS devices. METHODS: Sheep were implanted with linear epidural SCS leads. After a stimulating pulse, electrodes recorded ECAPs sequentially as they propagated orthodromically or antidromically. After filtering, amplification, and signal processing, ECAP amplitude and dispersion (width) was measured, and conduction velocity was calculated. Similar clinical data was also collected. A single-neuron computer model that simulated large-diameter sensory axons was used to explore and explain the observations. RESULTS: ECAPs, both animal and human, have a triphasic structure, with P1, N1, and P2 peaks. Conduction velocity in sheep was 109 ms-1 , which indicates that the underlying neural population includes fibers of up to 20 µm in diameter. For travel in both directions, propagation distance was associated with decrease in amplitude and increase in dispersion. Importantly, characteristics of these changes shifted abruptly at various positions along the cord. DISCUSSION: ECAP dispersion increases with propagation distance due to the contribution of slow-conducting small-diameter fibers as the signal propagates away from the source. An analysis of the discontinuities in ECAP dispersion changes with propagation revealed that these are due to the termination of smaller-diameter, slower-conducting fibers at corresponding segmental levels. The implications regarding SCS lead placement, toward the goal of maximizing clinical benefit while minimizing side-effects, are discussed. CONFLICT OF INTEREST: John Parker is the founder and CEO of Saluda Medical and holds stock options. Milan Obradovic, Nastaran Hesam Shariati, Dean M. Karantonis, Peter Single, James Laird-Wah, Robert Gorman and Mark Bickerstaff are employees of Saluda Medical with stock options. At the time the data was collected for the study, Prof. Cousins was a paid consultant for Saluda Medical. John Parker, Milan Obradovic, Dean Karantonis, James Laird-Wah, Robert Gorman and Peter Single are co-inventors in one or more patents related to the topics discussed in this work.

Neuronal atlas of the dorsal horn defines its architecture and links sensory input to transcriptional cell types.

The dorsal horn of the spinal cord is critical to processing distinct modalities of noxious and innocuous sensation, but little is known of the neuronal subtypes involved, hampering efforts to deduce principles governing somatic sensation. Here we used single-cell RNA sequencing to classify sensory neurons in the mouse dorsal horn. We identified 15 inhibitory and 15 excitatory molecular subtypes of neurons, equaling the complexity in cerebral cortex. Validating our classification scheme in vivo and matching cell types to anatomy of the dorsal horn by spatial transcriptomics reveals laminar enrichment for each of the cell types. Neuron types, when combined, define a multilayered organization with like neurons layered together. Employing our scheme, we find that heat and cold stimuli activate discrete sets of both excitatory and inhibitory neuron types. This work provides a systematic and comprehensive molecular classification of spinal cord sensory neurons, enabling functional interrogation of sensory processing.

Effects of naftopidil on inhibitory transmission in substantia gelatinosa neurons of the rat spinal dorsal horn in vitro.

OBJECTIVE: Naftopidil is used clinically for the treatment of voiding disorders in benign prostatic hyperplasia. Previous in vivo experiments in which naftopidil was applied intrathecally abolished rhythmic bladder contraction, suggesting that naftopidil might inhibit a voiding reflex through interaction with spinal dorsal horn neurons. Here we aimed to clarify the mechanism of action of naftopidil on dorsal horn neurons. METHODS: Whole-cell patch-clamp recordings were performed using substantia gelatinosa neurons of adult rat spinal cord slices. Miniature or evoked inhibitor and excitatory postsynaptic currents (IPSCs and EPSCs, respectively) were analyzed. RESULTS: Bath-applied naftopidil increased the frequency but not the amplitude of miniature IPSCs (mIPSCs) in 38% of neurons tested; in contrast, the effect of naftopidil on miniature EPSCs (mEPSCs) were mild and observed in only 2 out of 19 neurons. Naftopidil enhanced the amplitude of both GABAergic and glycinergic evoked-IPSCs (eIPSCs) that were elicited by focal stimuli in the presence of either the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV). CONCLUSIONS: Although naftopidil was developed as an alpha-1 adrenoceptor antagonist, our previous spinal cord slice experiments showed that the activation of an alpha-1 adrenoceptor in substantia gelatinosa increases the frequency of mIPSCs. This result suggested that, under our conditions, naftopidil may interact with a receptor(s) other than an alpha-1 adrenoceptor in the spinal dorsal horn. The present results suggested that naftopidil enhances the release of GABA and glycine by activating inhibitory interneuron terminals in the spinal dorsal horn via a receptor other than an alpha-1 adrenoceptor, thereby modulating sensory transmission in the substantia gelatinosa.

Anatomic study and clinical significance of the dorsal meningovertebral ligaments of the thoracic dura mater.

STUDY DESIGN: A dissection-based study of 18 embalmed thoracic specimens. OBJECTIVE: To investigate the properties and clinical significance of the dorsal meningovertebral ligaments of the thoracic dura mater. SUMMARY OF BACKGROUND DATA: Previously, we performed a comprehensive anatomic study on the dorsal meningovertebral ligaments in the lumbosacral and cervical regions, whereby we concluded that the ligaments were an anatomic factor leading to dural laceration and hemorrhage during flavectomy and laminectomy. Unfortunately, thus far, no systematic anatomic study has been undertaken to examine the dorsal meningovertebral ligaments of the thoracic dura mater. METHODS: Eighteen adult embalmed cadavers were studied, and the morphology, orientation, attachment site, and distribution traits of the dorsal meningovertebal ligaments were observed. In addition, the length, width, or diameter and thickness of the ligaments were measured using a Vernier caliper. Two meningovertebal ligaments were removed for histological examination. RESULTS: In the thoracic region, the dorsal meningovertebral ligaments anchored the dura mater to the lamina or ligamentum flavum. The meningovertebral ligaments displayed a relatively even distribution along the upper thoracic region (T1-T7) and a gradual increase in frequency in the lower thoracic region from T7 to T12. The meningovertebral ligaments protrude into the dura and correspondingly become an integral part of the dura. Some ligaments are accompanied by or are attached to blood vessels. Histological examination of the meningovertebral ligaments revealed fibrous connective tissue. CONCLUSION: The dorsal meningovertebral ligaments exist between the dural sac and ligamentum flavum or lamina in the thoracic spine. Based on their anatomic features, meningovertebral ligaments may be one potential cause for dural laceration and epidural hemorrhage. We propose that, during thoracic flavectomy and laminectomy, the meningovertebral ligaments should first be identified and properly handled, thereby minimizing the occurrence of relevant complications. LEVEL OF EVIDENCE: N/A.

Anatomy of the spinal dorsal root entry zone: its clinical significance.

BACKGROUND: The posterolateral sulcus (PLS) is an important surgical landmark, especially for DREZ (dorsal root entry zone) operations. METHODS: The present study aimed to show the variations of the PLS using human spinal cord histological sections and report the variability in the number of dorsal rootlets of the spinal nerves in each the spinal cord segment. Further, measure the height and width of the dorsal horn on histological sections for cervical, thoracic, and lumbar levels. RESULTS: The results of the present study showed various patterns of PLS 1.clearly present PLS, 2. short PLS, 3. absent PLS or 4. irregular PLS. Height and width measurements of the dorsal horn showed that the average width was greatest at lower cervical (0.48 ± 0.04 mm) and least at lower thoracic levels (0.41 ± 0.04 mm), whereas the average height was greatest at upper cervical (3.0 ± 0.06 mm) and smallest at lower lumbar levels (1.8 ± 0.08 mm). The average number of rootlets varied considerably, at cervical level it was 7.6 ± 1.4 mm, at thoracic 6.6 ± 0.8 mm and at lumbar 6.1 ± 0.4 mm. CONCLUSIONS: The detailed anatomy of the variations of the PLS and the average number of rootlets at each spinal level can increase the success of regional surgery. Further, fine measurements on histological sections can give detailed knowledge on the size necessary for lesioning in DREZ operations.