Thalamic Pain Research Articles

Development and pharmacological verification of a new mouse model of central post-stroke pain

Central post-stroke pain (CPSP) including thalamic pain is one of the most troublesome sequelae that can occur after a cerebrovascular accident. Although the prevalence of CPSP among stroke patients is relatively low, the persistent, often treatment-refractory, painful sensations can be a major problem and decrease the affected patient's quality of life. To better understand of the pathophysiological basis of CPSP, we developed and characterized a new mouse model of thalamic CPSP. This model is based on a hemorrhagic stroke lesion with collagenase in the ventral posterolateral nucleus of the thalamus. Histopathological analysis indicated that the thalamic hemorrhage produced a relatively confined lesion that destroys the tissue within the initial bleed, and also showed the presence of activated microglia adjacent to the core of hemorrhagic lesions. Behavioral analysis demonstrated that the animals displayed diclofenac-, morphine- or pregabalin-resistant mechanical allodynia and thermal hyperalgesia of the hind paw contralateral to the lesion for over 112 days. However, we found that minocycline, a microglial inhibitor, significantly ameliorated mechanical allodynia and thermal hyperalgesia. These results suggest that this model might be proved as a useful animal model for studying the neuropathology of thalamic syndrome, and developing improved therapeutics for CPSP.

Cognitive and behavioral deficits following bilateral thalamic stroke: A longitudinal study

We describe behavioral and neuropsychological outcome of a patient (N.S.), who showed a bilateral paramedian thalamic ischemic lesion, with particular reference to the longitudinal evolution of topographical disorientation (TD) and confabulations. We report clinical neuropsychological/behavioral data over a 43-month follow-up. The results show early after the stroke a severe amnesic-confabulatory syndrome with dysexecutive deficits, associated with memory disorders both for visuo-spatial and verbal materials and TD both for known and new places. Behavioral disinhibition and anosognosia for cognitive deficits were also observed.All cognitive impairments have been recovered during the long-term follow-up.Bilateral paramedian thalamic infarcts often lead to severe and long-lasting neurological and cognitive impairments. Only a few cases showed good recovery. Our patient represents an interesting and uncommon case of bilateral paramedian thalamic syndrome with a significant neuropsychological recovery.

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.

Comparison of fMRI BOLD Response Patterns by Electrical Stimulation of the Ventroposterior Complex and Medial Thalamus of the Rat

The objective of this study was to compare the functional connectivity of the lateral and medial thalamocortical pain pathways by investigating the blood oxygen level-dependent (BOLD) activation patterns in the forebrain elicited by direct electrical stimulation of the ventroposterior (VP) and medial (MT) thalamus. An MRI-compatible stimulation electrode was implanted in the VP or MT of α-chloralose-anesthetized rats. Electrical stimulation was applied to the VP or MT at various intensities (50 µA to 300 µA) and frequencies (1 Hz to 12 Hz). BOLD responses were analyzed in the ipsilateral forelimb region of the primary somatosensory cortex (iS1FL) after VP stimulation and in the ipsilateral cingulate cortex (iCC) after MT stimulation. When stimulating the VP, the strongest activation occurred at 3 Hz. The stimulation intensity threshold was 50 µA and the response rapidly peaked at 100 µA. When stimulating the MT, The optimal frequency for stimulation was 9 Hz or 12 Hz, the stimulation intensity threshold was 100 µA and we observed a graded increase in the BOLD response following the application of higher intensity stimuli. We also evaluated c-Fos expression following the application of a 200-µA stimulus. Ventroposterior thalamic stimulation elicited c-Fos-positivity in few cells in the iS1FL and caudate putamen (iCPu). Medial thalamic stimulation, however, produced numerous c-Fos-positive cells in the iCC and iCPu. The differential BOLD responses and c-Fos expressions elicited by VP and MT stimulation indicate differences in stimulus-response properties of the medial and lateral thalamic pain pathways.

La maladie de Cushing

Red ear syndrome (RES) is characterized by recurrent unilateral or bilateral painful attacks of the external ear, accompanied by ear redness, burning, or warmth. Proposed etiologies of this rare condition include dysregulation of sympathetic outflow, upper cervical pathology, glossopharyngeal and trigeminal neuralgia, TMJ dysfunction, thalamic syndrome, and primary headache syndromes. Idiopathic cases also exist in the literature. Pediatric cases are particularly rare and more commonly associated with migraine. Given the various potential etiologies, no single treatment is effective in all cases. This paper summarizes the current understanding and management of RES, and describes a case of idiopathic pediatric RES.

Abstract 125: Repetitive Transcranial Magnetic Stimulation Once A Week Induces Sustainable Long-term Relief Of Post-stroke Pain

Introduction: Post-stroke thalamic pain is a serious problem for some patients after stroke, deteriorating their activities of daily life, and is often resistant to medical treatments. Surgical intervention, such as electrical motor cortex stimulation, has been reported to be effective, but only for 40-60% of the patients despite of invasive procedures and costly devices. For some patients with electrical motor cortex stimulation, continuous stimulation is not always essential while occasional stimulation, such as a few hours every several days, is enough for their pain control. Recently, repetitive transcranial magnetic stimulation (rTMS) is reported to relieve post-stroke pain transiently but effectively. Hypothesis: We assessed the hypothesis that rTMS of motor cortex, maintained once a week, could induce sustainable long-term pain relief in patients with medication-resistant post-stroke pain. Methods: Fifteen patients suffering from medication-resistant post-stroke pain after thalamic hemorrhagic stroke were included. rTMS (10 trains of 10-second 5Hz TMS pulses at 50-second intervals, 90% of active motor threshold) was delivered on the motor cortex of the affected side. The rTMS session was repeated once a week for more than 12 weeks. The effect of rTMS on pain was rated by patients using a visual analog scale (VAS). Result: Mean VAS (±SEM) before rTMS (baseline) was 6.4±0.4 and reduced gradually and significantly in accordance with rTMS sessions. The VAS 12 weeks later was 3.4±0.5. Nine of 15 patients (60%) reported reduction of three or more VAS points. Five patients suffering from paresthesia rather than pain showed less reduction of VAS compared to the others. In five patients, rTMS was continued for one year and the effect of pain relief was also sustained. Conclusion: rTMS of the motor cortex, when maintained once a week, can provide long-term pain relief in patients with medication-resistant post-stroke pain.

Cheiro-Oral Syndrome Secondary to Thalamic Infarction

Small thalamic infarcts can present with a variety of sensory deficits that can be difficult to diagnose clinically because of their seemingly disconnected manifestations. Here we report a case of a 55-year-old man presenting with the clinical findings of Cheiro-Oral syndrome, a pure sensory thalamic lacunar syndrome that clinically presents with contralateral sensory deficits of the fingers and hemimouth. This report highlights both common and unusual clinical presentations of isolated thalamic infarctions, correlating clinical symptomatology with anatomic localization. In patients with such findings on examination, thalamic infarction should be considered, with a thorough workup initiated to both confirm the diagnosis and optimally reduce future stroke risk.

Thalamic Metabolism and Restless Legs Syndrome

Researchers at University of Bologna, Italy, evaluated medial thalamus metabolism and structural integrity in 23 patients with restless legs syndrome and 19 healthy controls.

Pure sensory syndromes and post-stroke pain secondary to bilateral thalamic lacunar infarcts: a case report

IntroductionPatients often complain about sensory symptoms that appear to the doctor as harmless, and reassurances are often given. Sensory strokes may easily be ignored.Case presentationA 48-year-old Caucasian woman with insulin-dependent diabetes and hyperlipidemia experienced symptoms that progressed within hours to a complete left-sided hemisensory syndrome. This was caused by a lacunar infarct in the ventral posterior tier nuclei of the right thalamus. A few days later she gradually developed an almost identical, but incomplete hemisensory syndrome on the opposite side caused by a corresponding lacune in the left thalamus. Severe persistent and paroxysmal pain on both sides of the body became disabling.ConclusionSmall strokes only affecting the somatosensory system should not be underestimated. Neuropathic pain may result. Probably unique in the present case is the demonstration of bilateral thalamic pain secondary to two almost identical thalamic infarcts. Small vessel disease (microatheroma or lipohyalinosis) was the most likely cause of the lacunes. One can only speculate if there was an occlusion in two separate thalamic perforators, or in a single dominant artery supplying the bilateral thalami.

Clinical efficacy observation of thalamic pain treated with acupuncture under the guidance of evidence-based medicine

ObjectiveTo study the feasibility of the crossover trial design and the minimal imbalance index random distribution method in the clinical small-sample-size randomized controlled trial (RCT) research of thalamic pain treated with acupuncture under the guidance of evidence-based medicine (EBM). MethodsThe crossover trial design was adopted. Eleven cases with the definite diagnosis were randomized into a program-I group (6 cases, treated with acupuncture before western medicine) and a program-ll group (5 cases, treated with western medicine before acupuncture) according to the minimal imbalance index method. In the statistical analysis, the groups were named as an acupuncture group and a western medicine group separately, 11 cases in each one. Acupuncture was applied to Xìmén (▪PC 4), Yīnxì (▪ HT 6), Xuèhăi (▪ SP 10), etc. In the control treatment, Carbamazepine was prescribed for oral administration. Either the duration of treatment or the wash-out period was 10 days. The visual analogue scale (VAS) was adopted for the efficacy assessment. ResultsThe total effective was 100.0% (11/11) after treatment in either group. The remarkably effective rates were 63.6% (7/11) and 36.4% (4/11) in the acupuncture group and the western medicine group separately, without statistically significant difference in comparison. ConclusionThe crossover trial design and the minimal imbalance index distribution method can accomplish RCT of the clinical acupuncture and moxibustion research with the small sample size involved. They can provide the high-quality evidences for clinical acupuncture research. Acupuncture therapy can achieve the same therapeutic effect as Carbamazepine, the common western medicine, and the efficacy of it is potentially superior to that of western medicine.

Improved Dexterity after Chronic Electrical Stimulation of the Motor Cortex for Central Pain: A Special Relevance for Thalamic Syndrome

Objectives: To demonstrate that motor cortex stimulation (MCS) could improve motor function in patients with neuropathic pain. Methods: In this prospective clinical study of 38 patients referred for MCS as treatment for their neuropathic pain, we collected any declaration of improvement in motor performance that could be attributed to MCS. Results: Ten patients (26%) declared a benefit in their motor function. Eight presented objective evidence of recovered dexterity for rapid alternating movements. A minor proportion had improvement in dystonic posture (n = 2), but none had detectable increased motor strength or tonus changes. Overall, 73% of the patients with limb ataxia declared a benefit after MCS. In 6 out of 10 patients (60%), the anatomic lesion responsible for pain was restricted to the lateral aspect of the thalamus. All of them had either clinical or electrophysiological evidence of lemniscal dysfunction (proprioceptive ataxia). No correlation was found between the scores of pain relief and the modification of motor status. The correlation between thalamic lesions and benefits in motor performance was significant (Fisher’s exact test, two-tailed, p = 0.0017). Conclusions: Up to 26% of patients estimated that MCS improved their motor outcome through recovered dexterity and in cases of lateral thalamic lesions.

Atypical presentation of thalamic post-stroke pain

Central post-stroke pain (CPSP) is a neuropathic pain syndrome occurring after a cerebrovascular accident. CPSP following a thalamic stroke (‘‘thalamic pain’’) is characterized by severe, persistent, paroxysmal, often intolerable pain on the hemiplegic side, unresponsive to any analgesic treatment [1]. We describe a patient in whom thalamic pain, which was the main presenting symptom of hemorrhagic stroke, was initially considered as peripheral neuropathic in nature, due to an atypical distribution of pain and the presence of muscular weakness. A 76-year-old man came to the Emergency Room for pain in his left thigh begun abruptly 3 days before and progressively increased in intensity, becoming intolerable. He had a history of hypertension, diabetes and chronic low back pain. On admission, neurological examination revealed moderate weakness in left hip flexion (Medical Research Council (MRC) 4-/5), absent deep tendon reflexes in lower limbs, allodynia and hyperpathia in the left anteromedial thigh, associated with a mild decrease in superficial sensation over the same region; sensation in response to pinprick, light touch and temperature, as well as vibratory sensation, was symmetrically decreased in feet and legs with a stocking distribution and a distal–proximal gradient (Fig. 1a). Subjective numbness associated with pain (described as severe, persistent, intolerable, deep and sometimes burning) over the left anteromedial thigh was reported. Brain computed tomography (CT) performed exclusively on the unfavorable vascular risk factor profile of the patient (diabetes and hypertension and acute onset of symptoms) showed a small hemorrhage in the right lateral thalamus ruptured in the homolateral ventricle (Fig. 1b). Neurophysiological study ruled out the coexistence of a lumbar radiculopathy/plexopathy or femoral mononeuropathy, showing only a sensory polyneuropathy. During the hospitalization, the pain progressively and spontaneously reduced, and completely disappeared within 1 week, without requiring pharmacological treatment. According to the literature [2], we did not use mannitol since there were no signs of increased intracranial pressure, and mean blood pressure was maintained below 130 mm Hg. In this patient, some neurological findings (absent deep reflexes in lower limbs, vibration and superficial sensation symmetrically decreased with a stocking distribution) were indicative of a distal, symmetrical sensory polyneuropathy, probably secondary to diabetes. Other findings were suggestive of a possible lumbar radiculopathy (history of chronic low back pain; weakness in left hip flexion; pain and mild decrease in superficial sensation over the left antero-medial thigh; absent knee reflexes). Overall, these findings could be compatible with an L2/L3 radiculopathy causing hip flexors’ weakness; alternatively, although less probable, given the muscular weakness confined to hip flexion and the sensory disturbance distribution, a diagnosis of partial lumbar plexopathy/femoral nerve mononeuropathy secondary to diabetes could be taken into consideration. The case we describe represents an atypical presentation of CPSP. F. Brigo F. Rossini (&) A. Stefani P. Tocco A. Fiaschi A. Salviati Section of Clinical Neurology, Department of Neurological, Neuropsychological, Morphological and Movement Sciences, University of Verona, Piazzale L.A. Scuro, 10, 37134 Verona, Italy e-mail: fabio.rossini@email.it

MRI might identify patients at risk of poststroke thalamic pain

MRI might identify patients at risk of poststroke thalamic pain

Assessing the risk of central post-stroke pain of thalamic origin by lesion mapping

Central post-stroke pain of thalamic origin is an extremely distressing and often refractory disorder. There are no well-established predictors for pain development after thalamic stroke, and the role of different thalamic nuclei is unclear. Here, we used structural magnetic resonance imaging to identify the thalamic nuclei, specifically implicated in the generation of central post-stroke pain of thalamic origin. Lesions of 10 patients with central post-stroke pain of thalamic origin and 10 control patients with thalamic strokes without pain were identified as volumes of interest on magnetic resonance imaging data. Non-linear deformations were estimated to match each image with a high-resolution template and were applied to each volume of interest. By using a digital atlas of the thalamus, we elucidated the involvement of different nuclei with respect to each lesion. Patient and control volumes of interest were summed separately to identify unique areas of involvement. Voxelwise odds ratio maps were calculated to localize the anatomical site where lesions put patients at risk of developing central post-stroke pain of thalamic origin. In the patients with pain, mainly lateral and posterior thalamic nuclei were affected, whereas a more anterior-medial lesion pattern was evident in the controls. The lesions of 9 of 10 pain patients overlapped at the border of the ventral posterior nucleus and the pulvinar, coinciding with the ventrocaudalis portae nucleus. The lesions of this area showed an odds ratio of 81 in favour of developing thalamic pain. The high odds ratio at the ventral posterior nucleus-pulvinar border zone indicates that this area is crucial in the pathogenesis of thalamic pain and demonstrates the feasibility of identifying patients at risk of developing central post-stroke pain of thalamic origin early after thalamic insults. This provides a basis for pre-emptive treatment studies.

Thumb, forefinger, and lip numbness: a distinctive thalamic lacunar syndrome

Thumb, forefinger, and lip numbness: a distinctive thalamic lacunar syndrome

Interactive Responses of a Thalamic Neuron to Formalin Induced Lasting Pain in Behaving Mice

Thalamocortical (TC) neurons are known to relay incoming sensory information to the cortex via firing in tonic or burst mode. However, it is still unclear how respective firing modes of a single thalamic relay neuron contribute to pain perception under consciousness. Some studies report that bursting could increase pain in hyperalgesic conditions while others suggest the contrary. However, since previous studies were done under either neuropathic pain conditions or often under anesthesia, the mechanism of thalamic pain modulation under awake conditions is not well understood. We therefore characterized the thalamic firing patterns of behaving mice in response to nociceptive pain induced by inflammation. Our results demonstrated that nociceptive pain responses were positively correlated with tonic firing and negatively correlated with burst firing of individual TC neurons. Furthermore, burst properties such as intra-burst-interval (IntraBI) also turned out to be reliably correlated with the changes of nociceptive pain responses. In addition, brain stimulation experiments revealed that only bursts with specific bursting patterns could significantly abolish behavioral nociceptive responses. The results indicate that specific patterns of bursting activity in thalamocortical relay neurons play a critical role in controlling long-lasting inflammatory pain in awake and behaving mice.

Tratamiento del dolor neuropático con lacosamida

Lacosamide is a new antiepileptic drug with a novel mechanism of action, as it selectively promotes the slow inactivation of voltage-dependent sodium channels without affecting fast inactivation. There are studies in the literature regarding its effectiveness in controlling neuropathic pain.We describe the use of intravenous lacosamide in the treatment of three patients with neuropathic pain: a woman with neuropathic pain in the first branch of the right trigeminal nerve during the acute phase of herpes zoster, a woman with central pain secondary to Dejerine-Roussy syndrome due to a malignant brain tumour, and a man with facial pain due to infiltration of the trigeminal nerve by a secondary lymphoma of the central nervous system. In the three cases, the administration of intravenous lacosamide has led to a considerable improvement in pain. The lacosamide dose has been 200 mg/day with excellent tolerability.Lacosamide can be an effective and well-tolerated alternative in the treatment of neuropathic pain and, moreover, its intravenous use can achieve pain control faster or be suitable when it is not tolerated orally.

Kyste neuroépithélial thalamo-mésencéphalique

Thalamo-mesencephalic neuroepithelial cysts are rare lesions of the central nervous system. They are thought to arise from neuroectoderm and are also referred to as ependymal cysts due to their origin. It can remain asymptomatic throughout life or rarely can cause symptoms. We describe a 42-year-old woman who presented with thalamic syndrome due to a neuroepithelial cyst of the thalamo-midbrain. Differential diagnosis is made with other cystic lesions in the brain. However a good analysis of imaging feature led to diagnosis. When the lesion is symptomatic, mini-invasive procedure is indicated.

Cerebral Blood Flow Alterations in Pain-Processing Regions of Patients with Fibromyalgia Using Perfusion MR Imaging

Widespread pain sensitivity in patients with FM suggests a CNS processing problem. The purpose of this study was to assess alterations in perfusion as measured by DSC in a number of brain regions implicated in pain processing between patients with FM and healthy controls. Twenty-one patients with FM and 27 healthy controls underwent conventional MR imaging and DSC. For DSC, 12 regions of interest were placed in brain regions previously implicated in pain processing. rCBF values were calculated for each region of interest. Subjects answered mood/pain coping questionnaires and underwent clinical/experimental pain assessment. There were significant correlations between the thalamic rCBF values and the pain-control beliefs of FM subjects. The strength of the relationship between clinical pain measures and thalamic rCBF values increased after adjusting for pain-control beliefs. There was a significantly different distribution pattern of rCBF values across various brain regions between the FM group and the healthy controls. There was a lower degree of correlation in the FM group between the thalamic rCBF values and the other brain regions relative to the healthy controls. Significant correlations were found between thalamic rCBF values and pain belief values. These data suggest that there are baseline alterations of brain perfusion in patients with FM. rCBF values of the thalami exhibited lower correlations with respect to other brain regions thought to be involved in pain processing compared with those in healthy controls.

Ludwig Edinger (1855–1918)

Ludwig Edinger, a German neurologist is considered as one of the founders of modern neuroanatomy. He was conferred the degree of Doctor of Medicine at the University of Strassburg. His observation of small living organisms under a microscope at an early age led him to study medicine. Edinger had many discoveries to his credit. He was the first to describe the ventral and dorsal spinocerebellar tracts, to distinguish between paleo-encephalon and neo-encephalon, and between paleo-cerebellum and neo-cerebellum. He coined the terms "gnosis" and "praxis," which were later adopted in psychological descriptions of agnosia and apraxia. He identified the Edinger-Westphal nucleus in 1885 and was the first to describe the syndrome of thalamic pain. Edinger worked with renowned clinicians and published a large number of papers. He founded the Neurological Institute at the Goethe University in Frankfurt, which is the oldest neurological Institute in Germany. Edinger was a rare combination of a profound scientist, a brilliant teacher, a fine artist, and a noted hypnotist. While at the height of his career, he underwent a surgery and died a few hours later. It was his last will that his brain should be dissected in his own institute. It showed extraordinarily well-developed occipital lobes as well as other unusual features.