Stereological study on the numerical plasticity of myelinated fibers and oligodendrocytes in the rat spinal cord with painful diabetic neuropathy.

Painful diabetic neuropathy may associate with nerve morphological plasticity in both peripheral and central nervous system. The aim of this study was to determine numerical changes of myelinated fibers in the spinothalamic tract region and oligodendrocytes in the spinal dorsal horn of rats with painful diabetic neuropathy and the effects of metformin on the above changes. Male Sprague-Dawley rats were randomly allocated into the control group (n = 7), the painful diabetic neuropathy group (n = 6) and the painful diabetic neuropathy treated with metformin group (the PDN + M group, n = 7), respectively. Twenty-eight days after medication, numbers of myelinated fibers in the spinothalamic tract and oligodendrocytes in the spinal dorsal horn were estimated by the optical disector (a stereological technique). Compared to the control group, number of myelinated fibers in the spinothalamic tract increased significantly in the painful diabetic neuropathy and PDN + M group, compared to the painful diabetic neuropathy group, number of myelinated fibers decreased in the PDN + M group (P < 0.05). As the oligodendrocyte in the spinal dorsal horn was considered, its number increased significantly in the painful diabetic neuropathy group compared to the control and the PDN + M group (P < 0.05), there was no significant difference between the control and the PDN + M group (P > 0.05). Our results indicate that painful diabetic neuropathy is associated with a serial of morphometric plasticity in the rat spinal cord including the numerical increase of the myelinated fibers in the spinothalamic tract and the oligodendrocytes in the spinal dorsal horn. The analgesic effect of metformin against painful diabetic neuropathy might be related to its adverse effects on the above morphometric plasticity.

Mechanisms of Below-Level Pain Following Spinal Cord Injury (SCI).

Mechanisms of below-level pain are discoverable as neural adaptations rostral to spinal injury. Accordingly, the strategy of investigations summarized here has been to characterize behavioral and neural responses to below-level stimulation over time following selective lesions of spinal gray and/or white matter. Assessments of human pain and the pain sensitivity of humans and laboratory animals following spinal injury have revealed common disruptions of pain processing. Interruption of the spinothalamic pathway partially deafferents nocireceptive cerebral neurons, rendering them spontaneously active and hypersensitive to remaining inputs. The spontaneous activity among these neurons is disorganized and unlikely to generate pain. However, activation of these neurons by their remaining inputs can result in pain. Also, injury to spinal gray matter results in a cascade of secondary events, including excitotoxicity, with rostral propagation of excitatory influences that contribute to chronic pain. Establishment and maintenance of below-level pain results from combined influences of injured and spared axons in the spinal white matter and injured neurons in spinal gray matter on processing of nociception by hyperexcitable cerebral neurons that are partially deafferented. A model of spinal stenosis suggests that ischemic injury to the core spinal region can generate below-level pain. Additional questions are raised about demyelination, epileptic discharge, autonomic activation, prolonged activity of C nocireceptive neurons, and thalamocortical plasticity in the generation of below-level pain. PERSPECTIVE: An understanding of mechanisms can direct therapeutic approaches to prevent development of below-level pain or arrest it following spinal cord injury. Among the possibilities covered here are surgical and other means of attenuating gray matter excitotoxicity and ascending propagation of excitatory influences from spinal lesions to thalamocortical systems involved in pain encoding and arousal.

Delayed-onset central poststroke pain due to degeneration of the spinothalamic tract following thalamic hemorrhage: A case report.

RATIONALE: Recent studies have used diffusion tensor tractography (DTT) to demonstrate that central poststroke pain (CPSP) was related to spinothalamic tract (STT) injury in patients with stroke. However, few studies have been reported about delayed-onset CPSP due to degeneration of the STT following a stroke. PATIENT'S CONCERNS: A 57-year-old female patient presented with right hemiparesis after stroke. Two weeks after onset, she did not report any pain. At approximately 6 months after onset, she reported pain in the right arm and leg, and the pain slowly intensified with the passage of time. At 14 months after onset, the characteristics and severity of her pain were assessed to be continuous pain without allodynia or hyperalgesia; tingling and cold-sensational pain in her right whole arm and leg (visual analog scale score: 5). DIAGNOSES: The patient was diagnosed as the right hemiparesis due to spontaneous thalamic hemorrhage. INTERVENTIONS: Clinical assessment and diffusion tensor imaging (DTI) were performed 2 weeks and 14 months after onset. OUTCOMES: She suffered continuous pain in her right whole arm and leg (visual analog scale score: 5). On DTT of the 2-week postonset DTI scans, the configuration of the STT was well-preserved in both hemispheres. However, in contrast to those 2-week postonset results, the 14-month postonset DTT results showed partial tearing and thinning in the left STT. Regardless, both the 2-week and 14-month postonset DTT showed that the left STT passed through the vicinity of the thalamic lesion. LESSONS: Diagnostic importance of performing a DTT-based evaluation of the STT in patients exhibiting delayed-onset CPSP following intracerebral hemorrhage.

A "matched" sensory reference can guide goal-directed movements of the affected hand in central post-stroke sensory ataxia.

Patients with central post-stroke sensory ataxia (CPSA) suffer from not only somatosensory dysfunction but also the ataxic movement disorder of the affected limb. These sensory and motor impairments possibly interfere each other, but such interference is still unclear. We evaluated smoothness of grasp movements in CPSA patients using a kinematic analysis, and verified the effect of somatosensory reference from the intact hand on grasp movements. Eight CPSA patients were enrolled. We recorded their reach-and-pinch movements of both affected and intact hands toward the tip of the 3-cm-diameter vertical bar, using a three-dimensional measurement system. When executing these movements of one hand, the patients simultaneously pinched the same diameter bar as the goal tip (matched-reference condition: Matched-Ref) or the 5-cm-diameter thicker bar (mismatched-reference condition: Mismatched-Ref) by the other hand. The normalized jerk index (i.e., movement smoothness) of the affected hand was disturbed compared with the intact hand. The kinematic data of the finger opening and closing phases were also disturbed. These disturbances were partially improved with Matched-Ref but not Mismatched-Ref of the intact hand. We successfully evaluated the features of CPSA, indicating that the somatosensory reference method could be useful for rehabilitation in sensory ataxia.

Clinical, pathological and functional characterization of riboflavin-responsive neuropathy.

Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy.

Microstructural mechanisms of analgesia in percutaneous cervical cordotomy revealed by diffusion tensor imaging.

The purpose of this study is to demonstrate the potential of diffusion tensor imaging (DTI) to reveal structural mechanisms underlying spinal ablative procedures, including percutaneous radiofrequency cordotomy (PRFC). PRFC is a surgical procedure that produces analgesia through focal ablation of the lateral spinothalamic tract (STT), thereby interrupting the flow of pain information from the periphery to the brain. To date, studies regarding mechanisms of analgesia after PRFC have been limited to postmortem cadaveric dissection and histology. However, with recent advances in DTI, the opportunity has arisen to study the STT non-invasively in vivo. In this technical note, an individual with successful pain relief following unilateral STT PRFC was examined using DTI, with the contralateral STT serving as an internal control. PRFC substantially reduced rostrocaudal directional DTI signal in the STT from the lesion in the cervical spinal cord through the pons and mesencephalon. Our findings confirm that focal ablation and anterograde degeneration accompany the analgesic effects of PRFC. In vivo imaging of the STT with DTI may contribute to surgical targeting for PRFC procedures, better understanding of the therapeutic and untoward effects of PRFC, and a deeper understanding of spinothalamic contributions to nociception.

Delayed-Onset Central Pain due to Degeneration of Ischemic Transcallosal Fibers After Corpus Callosum Hemorrhage.

AIMS: A patient developed delayed-onset central pain due to degeneration of the spinothalamic tract resulting from degeneration of the ischemic transcallosal fibers, in the aftermath of a corpus callosum (CC) hemorrhage. The detection and diagnosis of these lesions using diffusion tensor tractography are described. METHODS: A 59-yr-old man underwent conservative management for hemorrhages in the CC and lateral ventricle that resulted from hitting his head against a wall while falling. He began to feel pain in his right upper and lower extremities approximately 1½ yrs after the initial injury. The pain was characterized as constant tingling, numb, and cool sensation without allodynia or hyperalgesia (visual analogue scale score, 5). RESULTS: Disruption of transcallosal fibers in the genu and isthmus of the CC was observed on diffusion tensor tractography 1 mo after the initial injury. By 3 yrs, the diffusion tensor tractography showed that transcallosal fibers in the isthmus (67.8%-77.9%) of the CC had disappeared, and the left spinothalamic tract had become thinner. CONCLUSION: The results suggest that central pain can occur without direct injury of the spinothalamic tract and point up the need for evaluation of the spinothalamic tract and transcallosal fibers in patients with a CC lesion who complain of central pain.

Degeneration of an injured spinothalamic tract in a patient with mild traumatic brain injury.

OBJECTIVES: This study reports on a patient who developed degeneration of an injured spinothalamic tract (STT) detected on diffusion tensor tractography (DTT) following mild traumatic brain injury (TBI). CASE DESCRIPTION: A 56-year-old female had suffered from head trauma resulting from a pedestrian car accident. The patient did not experience loss of consciousness or post-traumatic amnesia and the patient's Glasgow Coma Scale score was 15. She had begun to feel pain in her left hand and foot at ~ 7 days after onset. The characteristics and severity of pain were as follows: constant tingling and pricking sensation without allodynia or hyperalgesia (Visual Analogue Scale score: 3~4). No specific focal lesion was observed on brain and spine MRI and an electromyography study showed no evidence of peripheral nerve injury or radiculopathy. At 6 months after onset, the central pain in the left hand and foot became aggravated, with a Visual Analogue Scale score of 6. RESULTS: On 1-month DTT, partial tearing was observed in both STTs. In contrast, both partially torn STTs had become atrophy on 9-month DTT. CONCLUSIONS: This study recommends further studies conducted on the prognosis (regeneration or degeneration) of injured STTs and on the effect of change of an injured STT on central pain.

Thalamic Reorganization in Chronic Patients With Intracerebral Hemorrhage: A Retrospective Cross-Sectional Study.

The aim of this study was to investigate changes of synaptic area of the spinothalamic tract and its thalamocortical pathway (STT) in the thalamus in chronic patients with putaminal hemorrhage.Twenty four patients with a lesion in the ventral posterior lateral nucleus (VPL) of the thalamus following putaminal hemorrhage were recruited for this study. The subscale for tactile sensation of the Nottingham Sensory Assessment (NSA) was used for the determination of somatosensory function. Diffusion tensor tractography of the STT was reconstructed using the Functional Magnetic Resonance Imaging of the Brain Software Library. We classified patients according to 2 groups: the VPL group, patients whose STTs were synapsed in the VPL; and the non-VPL group, patients whose STTs were synapsed in other thalamic areas, except for the VPL.Thirteen patients belonged to the VPL group, and 8 patients belonged to the non-VPL group. Three patients were excluded from grouping due to interrupted integrity of the STTs. The tactile sensation score of the NSA in the non-VPL group (10.50 ±â€Š0.93) was significantly decreased compared with that of the VPL group (19.45 ±â€Š1.33) (P < 0.05).We found that 2 types of patient had recovered via the VPL area or other areas of the STT. It appears that patients who showed shifting of the thalamic synaptic area of the STT might have recovered by the process of thalamic reorganization following thalamic injury. In addition, thalamic reorganization appears to be related to poorer somatosensory outcome.

Oligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice.

Mechanisms underlying central neuropathic pain are poorly understood. Although glial dysfunction has been functionally linked with neuropathic pain, very little is known about modulation of pain by oligodendrocytes. Here we report that genetic ablation of oligodendrocytes rapidly triggers a pattern of sensory changes that closely resemble central neuropathic pain, which are manifest before overt demyelination. Primary oligodendrocyte loss is not associated with autoreactive T- and B-cell infiltration in the spinal cord and neither activation of microglia nor reactive astrogliosis contribute functionally to central pain evoked by ablation of oligodendrocytes. Instead, light and electron microscopic analyses reveal axonal pathology in the spinal dorsal horn and spinothalamic tract concurrent with the induction and maintenance of nociceptive hypersensitivity. These data reveal a role for oligodendrocytes in modulating pain and suggest that perturbation of oligodendrocyte functions that maintain axonal integrity can lead to central neuropathic pain independent of immune contributions.

Aromatase inhibition exacerbates pain and reactive gliosis in the dorsal horn of the spinal cord of female rats caused by spinothalamic tract injury.

Central pain syndrome is characterized by severe and excruciating pain resulting from a lesion in the central nervous system. Previous studies have shown that estradiol decreases pain and that inhibitors of the enzyme aromatase, which synthesizes estradiol from aromatizable androgens, increases pain sensitivity. In this study we have assessed whether aromatase expression in the dorsal horns of the spinal cord is altered in a rat model of central pain syndrome, induced by the unilateral electrolytic lesion of the spinothalamic tract. Protein and mRNA levels of aromatase, as well as the protein and mRNA levels of estrogen receptors α and ß, were increased in the dorsal horn of female rats after spinothalamic tract injury, suggesting that the injury increased estradiol synthesis and signaling in the dorsal horn. To determine whether the increased aromatase expression in this pain model may participate in the control of pain, mechanical allodynia thresholds were determined in both hind paws after the intrathecal administration of letrozole, an aromatase inhibitor. Aromatase inhibition enhanced mechanical allodynia in both hind paws. Because estradiol is known to regulate gliosis we assessed whether the spinothalamic tract injury and aromatase inhibition regulated gliosis in the dorsal horn. The proportion of microglia with a reactive phenotype and the number of glial fibrillary acidic protein-immunoreactive astrocytes were increased by the injury in the dorsal horn. Aromatase inhibition enhanced the effect of the injury on gliosis. Furthermore, a significant a positive correlation of mechanical allodynia and gliosis in the dorsal horn was detected. These findings suggest that aromatase is up-regulated in the dorsal horn in a model of central pain syndrome and that aromatase activity in the spinal cord reduces mechanical allodynia by controlling reactive gliosis in the dorsal horn.

Frizzled3 is required for the development of multiple axon tracts in the mouse central nervous system.

Targeted mutation of the Frizzled3 (Fz3) gene in mice has been shown to disrupt the growth and guidance of a subset of peripheral and central axons. Here we used conditional deletion of Fz3 to explore the forebrain territories in which Fz3 action is required for the development of the anterior commissure and the corticothalamic, corticospinal, and thalamocortical tracts. Experiments with region-specific deletion of Fz3 using a variety of Cre lines show that proper routing of corticothalamic and thalamocortical axons in the internal capsule requires Fz3 expression in the ventral telencephalon. The pattern of defects among forebrain axon tracts that are induced by conditional deletion of Fz3 conforms closely to the pattern previously observed with analogous conditional deletion of Celsr3, implying a close mechanistic link between Fz3 and Celsr3 in axon guidance. We further found that several central nervous system axon tracts require Fz3 function as early as embryonic day 11.5, and that Fz3 is required for pathfinding by dopaminergic and serotonergic axons in the brain and by a subset of optic tract axons. In addition, conditional deletion of Fz3 in all tissues caudal to the neck eliminates the spinothalamic tract and the transmission of somatosensory information from the spinal cord to the brain, as determined by neuroanatomic tracing and behavioral testing.

Injury of the spinothalamic tract in a patient with mild traumatic brain injury: diffusion tensor tractography study.

OBJECTIVE: To report on a patient found to have injury of the spinothalamic tract on diffusion tensor tractography following traumatic brain injury. CASE DESCRIPTION: A 29-year-old male patient with head trauma resulting from a pedestrian car accident presented with pain in multiple areas (both subscapular areas, posterior head and neck, both upper trapezius areas, and the right arm and leg). His pain had not improved with various types of conservative management. RESULTS: Evaluations (conventional brain magnetic resonance imaging, electromyography, and whole spine magnetic resonance imaging), performed 2 years after the head trauma, did not reveal any specific abnormality. Fibromyalgia and myofascial pain syndrome were ruled out by physical examination. Injuries of the spinothalamic tracts in both hemispheres were observed on diffusion tensor imaging in terms of the configuration (thinning) and diffusion tensor tractography parameters (decreased fractional anisotropy or tract volume). CONCLUSION: Some of the pain in the trunk and extremities in this patient could be ascribed to central pain caused by injury of both spinothalamic tracts. We conclude that diffusion tensor tractography provides a useful means of detecting injury of the spinothalamic tract in patients with traumatic brain injury.

Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.

BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. RESULTS: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. CONCLUSIONS: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Relationship between somatosensory function and the spinothalamocortical pathway in chronic stroke patients.

Diffusion tensor tractography (DTT) allows for identification and evaluation of the spinothalamic tract and its thalamocortical pathway (STP). We attempted to investigate the relationship between tactile sensation and the STP in chronic stroke patients. We measured fractional anisotropy, mean diffusivity, and tract volume of the STP. The tactile sensation score of the affected side in patients with preserved STP integrity was higher compared with that of patients with an interrupted STP. The remaining volume and integrity of the STP in the affected hemisphere were important factors for tactile sensation of the affected side in chronic patients with intracerebral hemorrhage (ICH).

Role of microglia and astrocyte in central pain syndrome following electrolytic lesion at the spinothalamic tract in rats.

Central pain syndrome (CPS) is a debilitating state and one of the consequences of spinal cord injury in patients. Many pathophysiological aspects of CPS are not well documented. Spinal glia activation has been identified as a key factor in the sensory component of chronic pain. In this study, the role of glial subtypes in the process of CPS induced by unilateral electrolytic lesion of spinothalamic tract (STT) is investigated. Male rats received a laminectomy at T8-T9 and then unilateral electrolytic lesion centered on the STT. Thermal and mechanical thresholds as well as locomotor function were measured on days 0, 3, 7, 14, 21, and 28 post-injuries by tail flick, von Frey filament, and open field tests, respectively. To investigate the spinal glial activation following denervation in STT-lesioned groups, Iba1 and GFAP were detected by immunohistochemistry and Western blotting at the same time points. Data showed that STT lesion significantly decreased thermal pain at day 3 in comparison with sham groups. Significant bilateral allodynia appeared in hind paws at day 14 after spinal cord injury and continued to day 28 (P < 0.05). Additionally, electrolytic spinal lesion attenuated locomotor function of injured animals after 7 days (P < 0.05). In both histological assessments and Western blotting, Iba1 increased at days 3 and 7 while increased GFAP occurred from day 14 to 28 after lesion. It appears that microglial activation is important in the early stages of pain development and astrocytic activation occurs later. These events may lead to behavioral outcomes especially central neuropathic pain.

Decreased spinothalamic and dorsal column medial lemniscus-mediated function is associated with neuropathic pain after spinal cord injury.

Neuropathic pain (NP) after spinal cord injury (SCI) can significantly and negatively affect quality of life and is often refractory to currently available treatments. In order to find more effective therapeutic avenues, it would be helpful to identify the primary underlying pathophysiological mechanisms in each individual. The aim of the present study was to assess the relationship between the presence and severity of NP after SCI and measures of somatosensory function mediated via the dorsal column medial lemniscal (DCML) pathway and the spinothalamic tract (STT). Vibratory, mechanical, thermal, and pain thresholds measured in areas at and below the neurological level of injury (LOI) in persons with SCI and NP (SCI-NP, n=47) and in persons with SCI without NP (SCI-noNP, n=18) were normalized to data obtained from able-bodied pain-free control subjects (A-B, n=30). STT-mediated function at and below the LOI was significantly impaired in both SCI groups compared with A-B controls (p<0.001), but not significantly different between the two SCI groups (NP vs. no-NP). In contrast, the SCI-NP group had significantly greater impairment of DCML-mediated function at the LOI, as reflected by greater vibratory detection deficits (z=-3.89±0.5), compared with the SCI-noNP group (z=-1.95±0.7, p=0.034). Within the SCI-NP group, NP severity was significantly associated with increased thermal sensitivity below the LOI (r=0.50, p=0.038). Our results suggest that both impaired STT and DCML-mediated function are necessary for the development of NP after SCI. However, within the SCI-NP group, greater NP severity was associated with greater sensitivity to thermal stimuli below the LOI. This finding concurs with other studies suggesting that STT damage with some sparing is associated with NP.

The prevalence of central poststroke pain according to the integrity of the spino-thalamo-cortical pathway.

OBJECTIVES: Little is known about the prevalence of central poststroke pain (CPSP) according to the integrity of the spino-thalamo-cortical pathway (STP). Using diffusion tensor tractography, we investigated the prevalence of CPSP according to the integrity of the STP in patients with intracerebral hemorrhage. METHODS: We recruited 52 consecutive chronic patients and 10 normal control subjects. Patients were classified into two groups according to preservation of the integrity of the STP. Each group was divided into two subgroups according to the presence of CPSP. RESULTS: The preserved group included 34 patients [CPSP subgroup, 16 (47%) patients; non-CPSP subgroup, 18 (53%) patients], and 18 patients were enrolled into the disrupted group [CPSP subgroup, 3 (17%) patients; non-CPSP subgroup, 15 (83%) patients]. The fractional anisotropy and mean diffusivity values of the CPSP and non-CPSP subgroups of the preserved group were decreased and increased when compared with those of the control group, respectively (p < 0.05). CONCLUSIONS: We found that the prevalence of CPSP in patients with partial injury of the STP was higher than that of patients with complete injury of the STP. Partial injury of the STP appears to be more vulnerable to development of CPSP than complete injury of the STP in patients with intracerebral hemorrhage.

MRI of the central nervous system in MS patients with and without pain.

BACKGROUND: Central pain (CP) is a common symptom in MS. Multiple theories are present about the mechanism of CP. Previous studies suggested that lesion of the spinothalamic tract is a necessary condition for development of CP. No previous study has in detail evaluated the association between the specific site of demyelinations and the presence of CP in MS. OBJECTIVE: The study aimed to evaluate the location of plaques in MS patients with CP including a group of MS patients without pain as a reference group. METHODS: All patients underwent a bedside sensory examination and MRI of the brain and spinal cord. MR imaging was acquired on an 1.5 Tesla MR equipment. A trained neuroradiologist, blinded to pain status, evaluated the MRI. RESULTS: Thirteen MS patients with CP and 10 MS patients without pain were included. Allodynia and/or dysesthesia were more frequent in pain patients (11/13 vs. 1/10, P<0.01). No difference was found in the number of patients with plaques in spinothalamic tract, dorsal column-medial lemniscus, dorsolateral funiculus, grey substance, thalamus or capsula interna. A non-significantly lower number of pain patients had lesions in thalamo-cortical pathways (8/13 vs. 10/10, P=0.027). CONCLUSIONS: No association between CP and site of demyelinations was found, although a trend toward a higher prevalence of intact thalamo-cortical pathways was seen in pain patients. CP was associated with allodynia, suggesting central hyperexcitability.