scholarly journals Spinal neuron-glia-immune interaction in cross-organ sensitization

2020 ◽  
Vol 319 (6) ◽  
pp. G748-G760
Author(s):  
Liya Y. Qiao ◽  
Namrata Tiwari
Keyword(s):  
Spinal Cord ◽  
Glial Cells ◽  
Sensory Information ◽  
Spinal Nerve ◽  
Primary Afferents ◽  
Leg Pain ◽  
Spinal Neuron ◽  
Afferent Neurons ◽  
Satellite Glial Cells ◽  
Integrative Processing

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), historically considered as regional gastrointestinal disorders with heightened colonic sensitivity, are increasingly recognized to have concurrent dysfunction of other visceral and somatic organs, such as urinary bladder hyperactivity, leg pain, and skin hypersensitivity. The interorgan sensory cross talk is, at large, termed “cross-organ sensitization.” These organs, anatomically distant from one another, physiologically interlock through projecting their sensory information into dorsal root ganglia (DRG) and then the spinal cord for integrative processing. The fundamental question of how sensitization of colonic afferent neurons conveys nociceptive information to activate primary afferents that innervate distant organs remains ambiguous. In DRG, primary afferent neurons are surrounded by satellite glial cells (SGCs) and macrophage accumulation in response to signals of injury to form a neuron-glia-macrophage triad. Astrocytes and microglia are major resident nonneuronal cells in the spinal cord to interact, physically and chemically, with sensory synapses. Cumulative evidence gathered so far indicate the indispensable roles of paracrine/autocrine interactions among neurons, glial cells, and immune cells in sensory cross-activation. Dichotomizing afferents, sensory convergency in the spinal cord, spinal nerve comingling, and extensive sprouting of central axons of primary afferents each has significant roles in the process of cross-organ sensitization; however, more results are required to explain their functional contributions. DRG that are located outside the blood-brain barrier and reside upstream in the cascade of sensory flow from one organ to the other in cross-organ sensitization could be safer therapeutic targets to produce less central adverse effects.

Perspectives in Pain Research 2014: Neuroinflammation and glial cell activation: The cause of transition from acute to chronic pain?

2015 ◽  
Vol 6 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Brian E. Cairns ◽  
Lars Arendt-Nielsen ◽  
Paola Sacerdote
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Glial Cell ◽  
Schwann Cells ◽  
Glial Cells ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Dorsal Root ◽  
Satellite Glial Cells

AbstractBackgroundIt is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition.There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain. Activated Schwann cells, satellite glial cells, microglia, and astrocytes may contribute to pain sensitivity by releasing cytokines leading to altered neuronal function in the direction of sensitisation.Aims of this perspective paper1) Highlight the complex but important recent achievement in the area of neuroinflammation and pain at spinal cord level and in the dorsal root ganglion.2) Encourage further research which hopefully may provide better understanding of new key elements driving the transition from acute to chronic pain.Recent results in the area of neuroinflammation and painFollowing a sciatic nerve injury, local macrophages, and Schwann cells trigger an immune response immediately followed by recruitment of blood-derived immune cells. Schwann cells, active resident, and infiltrating macrophages release proinflammatory cytokines. Proinflammatory cytokines contribute to axonal damage and also stimulate spontaneous nociceptor activity. This results in activation of satellite glial cells leading to an immune response in the dorsal root ganglia driven by macrophages, lymphocytes and satellite cells. The anterograde signalling progresses centrally to activate spinal microglia with possible up regulation of glial-derived proinflammatory/pronociceptive mediators.An important aspect is extrasegmental spreading sensitisation where bilateral elevations in TNF-α, IL-6, and IL-10 are found in dorsal root ganglion in neuropathic models. Similarly in inflammatory pain models, bilateral up regulation occurs for TNF-α, IL-1 β, and p38 MAPK. Bilateral alterations in cytokine levels in the DRG and spinal cord may underlie the spread of pain to the uninjured side.An important aspect is how the opioids may interact with immune cells as opioid receptors are expressed by peripheral immune cells and thus can induce immune signaling changes. Furthermore, opioids may stimulate microglia cells to produce proinflammatory cytokines such as IL-1.ConclusionsThe present perspective paper indicates that neuroinflammation and the associated release of pro-inflammatory cytokines in dorsal root ganglion and at the spinal cord contribute to the transition from acute to chronic pain. Neuroinflammatory changes have not only been identified in the spinal cord and brainstem, but more recently, in the sensory ganglia and in the nerves as well. The glial cell activation may be responsible for contralateral spreading and possible widespread sensitisation.ImplicationsCommunication between glia and neurons is proposed to be a critical component of neuroinflammatory changes that may lead to chronic pain. Sensory ganglia neurons are surrounded by satellite glial cells but how communication between the cells contributes to altered pain sensitivity is still unknown. Better understanding may lead to new possibilities for (1) preventing development of chronic pain and (2) better pain management.

scholarly journals Satellite Glial Cells Surrounding Primary Afferent Neurons Are Activated and Proliferate during Monoarthritis in Rats: Is There a Role for ATF3?

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e108152 ◽  
Author(s):  
Diana Sofia Marques Nascimento ◽  
José Manuel Castro-Lopes ◽  
Fani Lourença Moreira Neto
Keyword(s):  
Glial Cells ◽  
Afferent Neurons ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Satellite Glial Cells

scholarly journals Genetically identified spinal interneurons integrating tactile afferents for motor control

2015 ◽  
Vol 114 (6) ◽  
pp. 3050-3063 ◽  
Author(s):  
Tuan V. Bui ◽  
Nicolas Stifani ◽  
Izabela Panek ◽  
Carl Farah
Keyword(s):  
Spinal Cord ◽  
Motor Control ◽  
Sensory Information ◽  
Spinal Neuron ◽  
Spinal Neurons ◽  
Tactile Information ◽  
Spinal Interneurons ◽  
Motor Circuits ◽  
Neuron Populations ◽  
Genetic Techniques

Our movements are shaped by our perception of the world as communicated by our senses. Perception of sensory information has been largely attributed to cortical activity. However, a prior level of sensory processing occurs in the spinal cord. Indeed, sensory inputs directly project to many spinal circuits, some of which communicate with motor circuits within the spinal cord. Therefore, the processing of sensory information for the purpose of ensuring proper movements is distributed between spinal and supraspinal circuits. The mechanisms underlying the integration of sensory information for motor control at the level of the spinal cord have yet to be fully described. Recent research has led to the characterization of spinal neuron populations that share common molecular identities. Identification of molecular markers that define specific populations of spinal neurons is a prerequisite to the application of genetic techniques devised to both delineate the function of these spinal neurons and their connectivity. This strategy has been used in the study of spinal neurons that receive tactile inputs from sensory neurons innervating the skin. As a result, the circuits that include these spinal neurons have been revealed to play important roles in specific aspects of motor function. We describe these genetically identified spinal neurons that integrate tactile information and the contribution of these studies to our understanding of how tactile information shapes motor output. Furthermore, we describe future opportunities that these circuits present for shedding light on the neural mechanisms of tactile processing.

scholarly journals Current understanding of trigeminal ganglion structure and function in headache

Cephalalgia ◽  
2018 ◽  
Vol 39 (13) ◽  
pp. 1661-1674 ◽  
Author(s):  
Karl Messlinger ◽  
Andrew F Russo
Keyword(s):  
Glial Cells ◽  
Trigeminal Ganglion ◽  
Ganglion Cells ◽  
Sensory Information ◽  
Calcitonin Gene Related Peptide ◽  
Primary Headaches ◽  
Satellite Glial Cells ◽  
Related Peptide ◽  
Signaling Mechanisms ◽  
Calcitonin Gene

Introduction The trigeminal ganglion is unique among the somatosensory ganglia regarding its topography, structure, composition and possibly some functional properties of its cellular components. Being mainly responsible for the sensory innervation of the anterior regions of the head, it is a major target for headache research. One intriguing question is if the trigeminal ganglion is merely a transition site for sensory information from the periphery to the central nervous system, or if intracellular modulatory mechanisms and intercellular signaling are capable of controlling sensory information relevant for the pathophysiology of headaches. Methods An online search based on PubMed was made using the keyword “trigeminal ganglion” in combination with “anatomy”, “headache”, “migraine”, “neuropeptides”, “receptors” and “signaling”. From the relevant literature, further references were selected in view of their relevance for headache mechanisms. The essential information was organized based on location and cell types of the trigeminal ganglion, neuropeptides, receptors for signaling molecules, signaling mechanisms, and their possible relevance for headache generation. Results The trigeminal ganglion consists of clusters of sensory neurons and their peripheral and central axon processes, which are arranged according to the three trigeminal partitions V1–V3. The neurons are surrounded by satellite glial cells, the axons by Schwann cells. In addition, macrophage-like cells can be found in the trigeminal ganglion. Neurons express various neuropeptides, among which calcitonin gene-related peptide is the most prominent in terms of its prevalence and its role in primary headaches. The classical calcitonin gene-related peptide receptors are expressed in non-calcitonin gene-related peptide neurons and satellite glial cells, although the possibility of a second calcitonin gene-related peptide receptor in calcitonin gene-related peptide neurons remains to be investigated. A variety of other signal molecules like adenosine triphosphate, nitric oxide, cytokines, and neurotrophic factors are released from trigeminal ganglion cells and may act at receptors on adjacent neurons or satellite glial cells. Conclusions The trigeminal ganglion may act as an integrative organ. The morphological and functional arrangement of trigeminal ganglion cells suggests that intercellular and possibly also autocrine signaling mechanisms interact with intracellular mechanisms, including gene expression, to modulate sensory information. Receptors and neurotrophic factors delivered to the periphery or the trigeminal brainstem can contribute to peripheral and central sensitization, as in the case of primary headaches. The trigeminal ganglion as a target of drug action outside the blood-brain barrier should therefore be taken into account.

scholarly journals Profiling the molecular signature of Satellite Glial Cells at the single cell level reveals high similarities between rodent and human

2021 ◽  
Author(s):  
Oshri Avraham ◽  
Alexander Chamessian ◽  
Rui Feng ◽  
Alexandra E Halevi ◽  
Amy M Moore ◽  
...  
Keyword(s):  
Single Cell ◽  
Glial Cells ◽  
Nerve Repair ◽  
Critical Role ◽  
Sensory Information ◽  
Model Systems ◽  
Molecular Signature ◽  
Single Cell Level ◽  
Cell Level ◽  
Satellite Glial Cells

Peripheral sensory neurons located in dorsal root ganglia relay sensory information from the peripheral tissue to the brain. Satellite glial cells (SGC) are unique glial cells that form an envelope completely surrounding each sensory neuron soma. This organization allows for close bidirectional communication between the neuron and it surrounding glial coat. Morphological and molecular changes in SGC have been observed in multiple pathological conditions such as inflammation, chemotherapy-induced neuropathy, viral infection and nerve injuries. There is evidence that changes in SGC contribute to chronic pain by augmenting neuronal activity in various rodent pain models. SGC also play a critical role in axon regeneration. Whether findings made in rodent model systems are relevant to human physiology have not been investigated. Here we present a detailed characterization of the transcriptional profile of SGC in mouse, rat and human at the single cell level. Our findings suggest that key features of SGC in rodent models are conserved in human. Our study provides the potential to leverage on rodent SGC properties and identify potential targets for the treatment of nerve repair and alleviation of painful conditions.

Sacral plexus disorder caused by a wooden toothpick in the rectum

2021 ◽  
Vol 14 (1) ◽  
pp. e238690
Author(s):  
Takuro Endo ◽  
Taku Sugawara ◽  
Naoki Higashiyama
Keyword(s):  
Lower Limb ◽  
Spinal Nerve ◽  
Leg Pain ◽  
Sacral Plexus ◽  
Lateral Recess ◽  
Lateral Recess Stenosis ◽  
Preoperative Ct ◽  
History Of ◽  
History Of Pain ◽  
The Right

A 67-year-old man presented with a 2-month history of pain in his right buttock and lower limb. MRI depicted right L5/S1 lateral recess stenosis requiring surgical treatment; however, preoperative CT showed an approximately 7 cm long, thin, rod-shaped structure in the rectum, which was ultimately determined to be an accidentally ingested toothpick. It was removed surgically 6 days after diagnosis, because right leg pain worsened rapidly. The pain disappeared thereafter, and the symptoms have not recurred since. The pain might have been localised to the right buttock and posterior thigh in the early stages because the fine tip of the toothpick was positioned to the right of the anterior ramus of the S2 spinal nerve. Although sacral plexus disorder caused by a rectal foreign body is extremely rare, physicians should be mindful to avoid misdiagnosis.

scholarly journals Brain fMRI during orientation selective epidural spinal cord stimulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonietta Canna ◽  
Lauri J. Lehto ◽  
Lin Wu ◽  
Sheng Sang ◽  
Hanne Laakso ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Stimulation ◽  
Pain Treatment ◽  
Positive Impact ◽  
Sensory Information ◽  
Activation Patterns ◽  
Promising Tool ◽  
Cord Injury ◽  
Epidural Spinal Cord Stimulation ◽  
Brain Fmri

AbstractEpidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.

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