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

AIMS: Neuropathic 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. METHODS: Micro-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. RESULTS: A 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. CONCLUSIONS: Neuropathic 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.

Identifying Discomplete Spinal Lesions: New Evidence from Pain-Autonomic Interaction in Spinal Cord Injury.

The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions; that is, residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared with objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively). Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%), and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relationship was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%). In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discerning STT lesion completeness might support the investigation of its association with neuropathic pain following SCI.

Cortico-spinal imaging to study pain.

Functional magnetic resonance imaging of the brain has helped to reveal mechanisms of pain perception in health and disease. Recently, imaging approaches have been developed that allow recording neural activity simultaneously in the brain and in the spinal cord. These approaches offer the possibility to examine pain perception in the entire central pain system and in addition, to investigate cortico-spinal interactions during pain processing. Although cortico-spinal imaging is a promising technique, it bears challenges concerning data acquisition and data analysis strategies. In this review, we discuss studies that applied simultaneous imaging of the brain and spinal cord to explore central pain processing. Furthermore, we describe different MR-related acquisition techniques, summarize advantages and disadvantages of approaches that have been implemented so far and present software that has been specifically developed for the analysis of spinal fMRI data to address challenges of spinal data analysis.

Theory of mind network in multiple Sclerosis: A double disconnection mechanism.

The relationship between cognitive and affective theory of mind (ToM), clinical variables, and brain tissue injury is still a subject of debate in multiple sclerosis (MS). By adopting a ToM Networks model, we investigated ToM performance, and brain imaging correlates in relapsing-remitting (RR) and progressive (Pr) MS. 16RR, 19Pr, and 21 healthy controls were assessed with both cognitive (CToM) and affective ToM (AToM) tests and neuropsychological tools and were evaluated with MRI. Cortical thickness, sub-cortical volumetry, and tract-based-spatial-statistics were analyzed. Our results reported a CToM deficit in Pr, correlated with attention. While no relation between gray matter and CToM was observed, a widespread correlation between CToM and normal-appearing white matter was found. In particular, we registered a significant positive correlation between CToM and fractional anisotropy in Superior and Inferior Longitudinal Fasciculus and right thalamic radiation tracts. Moreover, an inverse correlation between CToM and mean diffusivity of the right fronto-occipital fasciculus, bilateral superior longitudinal fasciculus, cortico-spinal, left uncinate, corpus callosum, and forceps minor tracts was also observed. This work highlighted a double disconnection mechanism in Pr MS affecting communication both (1) inside the ToM network and (2) between the ToM network and cognitive execution areas, likely explaining the deficit in cognitive ToM.

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.

Mesencephalotomy, How I Do It: Analysis of 34 Cases

The present paper aims to demystify the use of rostral mesencephalic reticulotomy (mesencephalotomy) in the treatment of chronic pain in cancer patients. A retrospective review of the medical records from the Central Pain and Stereotaxy Department of the A. C. Camargo Cancer Center, São Paulo, state of São Paulo, Brazil, between 2005 and 2012, was performed. Surgical indication was restricted to patients with cancer pain refractory to etiological and symptomatic treatments, > 2 months of expected survival, preserved cognition, and absence of coagulation disorders, of systemic infection, and of intracranial hypertension. We have selected 34 patients, with an average follow-up of 9.4 months, an average age of 54.3 years-old, and an average follow-up time until death of 6.4 months. Lung cancer was themost frequent diagnosis. Satisfactory and immediate pain relief was achieved in 91% of the cases, and 83% of these patients had no relapses. Among the complications, ocular movement disorder was the most frequent, but often transient. Permanent disturbances occurred in 8.8% of the cases (diplopia, rubral tremor, and paresthesia). Compared to the pharmacological treatment, mesencephalotomy was economically feasible, more effective, and improved quality of life. According to the data presented, it can be concluded that mesencephalotomy is a viable procedure for cancer pain control in selected cases.

Gamma-Band Oscillations Preferential for Nociception can be Recorded in the Human Insula.

Transient nociceptive stimuli elicit robust phase-locked local field potentials (LFPs) in the human insula. However, these responses are not preferential for nociception, as they are also elicited by transient non-nociceptive vibrotactile, auditory, and visual stimuli. Here, we investigated whether another feature of insular activity, namely gamma-band oscillations (GBOs), is preferentially observed in response to nociceptive stimuli. Although nociception-evoked GBOs have never been explored in the insula, previous scalp electroencephalography and magnetoencephalography studies suggest that nociceptive stimuli elicit GBOs in other areas such as the primary somatosensory and prefrontal cortices, and that this activity could be closely related to pain perception. Furthermore, tracing studies showed that the insula is a primary target of spinothalamic input. Using depth electrodes implanted in 9 patients investigated for epilepsy, we acquired insular responses to brief thermonociceptive stimuli and similarly arousing non-nociceptive vibrotactile, auditory, and visual stimuli (59 insular sites). As compared with non-nociceptive stimuli, nociceptive stimuli elicited a markedly stronger enhancement of GBOs (150-300 ms poststimulus) at all insular sites, suggesting that this feature of insular activity is preferential for thermonociception. Although this activity was also present in temporal and frontal regions, its magnitude was significantly greater in the insula as compared with these other regions.

Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys.

After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution cerebral blood volume-based functional magnetic resonance imaging (CBV-fMRI) mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6weeks after a mid-cervical level contralateral DC lesion. Both low and high intensity ES of digits revealed the expected somatotopy of the area 3b hand representation in pre-lesion monkeys, while in areas 1 and 3a, high intensity stimulation was more effective in activating somatotopic patterns. Six weeks post-lesion, and irrespective of the severity of loss of direct DC inputs (98%, 79%, 40%), somatosensory cortical area 3b of all three animals showed near complete recovery in terms of somatotopy and responsiveness to low and high intensity ES. However there was significant variability in the patterns and amplitudes of reactivation of individual digit territories within and between animals, reflecting differences in the degree of permanent and/or transient silencing of primary DC and secondary inputs 2weeks post-lesion, and their spatio-temporal trajectories of recovery between 2 and 6weeks. Similar variations in the silencing and recovery of somatotopy and responsiveness to high intensity ES in areas 3a and 1 are consistent with individual differences in damage to and recovery of DC and spinocuneate pathways, and possibly the potentiation of spinothalamic pathways. Thus, cortical deactivation and subsequent reactivation depends not only on the degree of DC lesion, but also on the severity and duration of loss of secondary as well as primary inputs revealed by low and high intensity ES.

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

Differential pain modulation properties in central neuropathic pain after spinal cord injury.

It seems that central neuropathic pain (CNP) is associated with altered abilities to modulate pain; whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution, enhanced pain excitation is associated with the intensity of chronic pain. We investigated the hypothesis that CNP is associated with decreased descending pain inhibition along with increased neuronal excitability and that both traits are associated with spinothalamic tract (STT) damage. Chronic spinal cord injury subjects with CNP (n = 27) and without CNP (n = 23) and healthy controls (n = 20) underwent the measurement of pain adaptation, conditioned pain modulation (CPM), tonic suprathreshold pain (TSP), and spatial summation of pain above injury level. Central neuropathic pain subjects also underwent at and below-lesion STT evaluation and completed the questionnaires. Central neuropathic pain subjects showed decreased CPM and increased enhancement of TSP compared with controls. Among CNP subjects, the dysfunction of CPM and pain adaptation correlated positively with the number of painful body regions. The magnitude of TSP and spatial summation of pain correlated positively with CNP intensity. STT scores correlated with CNP intensity and with TSP, so that the more affected the STT below injury level, the greater the CNP and TSP magnitude. It seems that CNP is associated with altered abilities to modulate pain, whereas dysfunction in descending pain inhibition is associated with the extent of chronic pain distribution and enhanced pain excitation is associated with the intensity of chronic pain. Thus, top-down processes may determine the spread of CNP, whereas bottom-up processes may determine CNP intensity. It also seems that the mechanisms of CNP may involve STT-induced hyperexcitability. Future, longitudinal studies may investigate the timeline of this scenario.

[Spinal cord stimulation for thalamic pain: Case report and review of the current literature]. / Hochzervikale Rückenmarkstimulation bei Thalamusschmerz : Fallbericht und Übersicht zur aktuellen Literatur.

BACKGROUND: Spinal cord stimulation (SCS) is an established procedure for treatment of chronic neuropathic pain of peripheral origin. The efficacy of SCS in case of central poststroke pain (CPSP), especially thalamic pain, has not been adequately proven. OBJECTIVES: The efficacy of SCS as an extracranial neurostimulation method for the management of central pain syndrome was investigated. MATERIALS AND METHODS: In this study, relevant pharmacological and nonpharmacological measures for central pain management were reviewed. A case of successful SCS for thalamic pain after ischemic insult is presented. Explanatory approaches of pathophysiological processes and a review of the current literature underline our results. RESULTS: In the case presented, SCS was found effective in the treatment of thalamic pain. CONCLUSION: The efficacy of SCS might be caused by segmental and supraspinal processes and collaboration of activating and inhibiting pathways. The integrity of the spinothalamic tract is mandatory. SCS is a treatment option for central pain syndrome, especially thalamic pain. Comparable studies confirm the potency of this technique. In contrast to other neuromodulation procedures spinal cord stimulation is less invasive, has a lower perioperative risk and is often less expensive. Further studies are needed to define its potential and role in the treatment of thalamic pain.

Quantitative sensory testing of temperature, pain, and touch in adults with Down syndrome.

The spinothalamic pathway mediates sensations of temperature, pain, and touch. These functions seem impaired in children with Down syndrome (DS), but have not been extensively examined in adults. The objective of the present study was to compare the spinothalamic-mediated sensory functions between adults with DS and adults from the general population and to examine in the DS group the relationship between the sensory functions and level of intellectual functioning. Quantitative sensory testing (QST) was performed in 188 adults with DS (mean age 37.5 years) and 142 age-matched control participants (median age 40.5 years). Temperature, pain, and touch were evaluated with tests for cold-warm discrimination, sharp-dull discrimination (pinprick), and tactile threshold, respectively. Level of intellectual functioning was estimated with the Social Functioning Scale for Intellectual Disability (intellectual disability level) and the Wechsler Preschool and Primary Scale of Intelligence--Revised (intelligence level). Overall, the difference in spinothalamic-mediated sensory functions between the DS and control groups was not statistically significant. However, DS participants with a lower intelligence level had a statistically significant lower performance on the sharp-dull discrimination test than DS participants with higher intelligence level (adjusted p=.006) and control participants (adjusted p=.017). It was concluded that intellectual functioning level is an important factor to take into account for the assessment of spinothalamic-mediated sensory functioning in adults with DS: a lower level could coincide with impaired sensory functioning, but could also hamper QST assessment.

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.

Syringomyelia in an older patient.

We describe the case of an 80-year-old man who presented with lower limb upper motor neurone weakness and spinothalamic tract sensory deficit secondary to previously undiagnosed syringomyelia. The case highlights the need for methodical history, examination and investigation in elderly patients to achieve diagnostic accuracy.

Treatment of medically refractory cancer pain with a combination of intrathecal neuromodulation and neurosurgical ablation: case series and literature review.

OBJECTIVE: Up to 90% of patients with advanced cancer experience intractable pain. For these patients, oral analgesics are the mainstay of therapy, often augmented with intrathecal drug delivery. Neurosurgical ablative procedures have become less commonly used, though their efficacy has been well-established. Unfortunately, little is known about the safety of ablation in the context of previous neuromodulation. Therefore, the aim of this study is to present the results from a case series in which patients were treated successfully with a combination of intrathecal neuromodulation and neurosurgical ablation. DESIGN: Retrospective case series and literature review. SETTING: Three institutions with active cancer pain management programs in the United States. METHODS: All patients who underwent both neuroablative and neuromodulatory procedures for cancer pain were surveyed using the visual analog scale prior to the first procedure, before and after a second procedure, and at long-term follow-up. Based on initial and subsequent presentation, patients underwent intrathecal morphine pump placement, cordotomy, or midline myelotomy. RESULTS: Five patients (2 male, 3 female) with medically intractable pain (initial VAS = 10) were included in the series. Four subjects were initially treated with intrathecal analgesic neuromodulation, and 1 with midline myelotomy. Each patient experienced recurrence of pain (VAS ≥ 9) following the initial procedure, and was therefore treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1; percutaneous radiofrequency cordotomy, N = 3), with significant long-term benefit (VAS 1-7). CONCLUSION: In cancer patients with medically intractable pain, intrathecal neuromodulation and neurosurgical ablation together may allow for more effective control of cancer pain.

Assessment of Spinothalamic Tract Function Beyond Pinprick in Spinal Cord Lesions: A Contact Heat Evoked Potential Study.

Background Although a mainstay of clinical sensory examination after damage in the spinal cord, pinprick sensation represents only one afferent modality conveyed in the spinothalamic tract. As an objective outcome, complementary information regarding spinothalamic tract conduction may be elucidated by measuring contact heat evoked potentials (CHEPs). Objective To assess the value of CHEPs to measure spinothalamic tract function in spinal cord disorders compared with pinprick scoring. Methods CHEPs were examined using a standard (35°C) and increased baseline (42°C) contact heat temperature. Pinprick sensation was rated as absent, impaired, or normal according to the International Standards for the Neurological Classification of Spinal Cord Injury. Results Fifty-nine dermatomes above, at, and below the sensory level of impairment were analyzed in 37 patients with defined spinal cord disorder. In dermatomes with absent or impaired pinprick sensation, CHEPs using a standard baseline temperature were mainly abolished (3/16 and 8/35, respectively). However, when applying an increased baseline temperature, CHEPs became recordable (absent: 11/16; impaired: 31/35). Furthermore, CHEPs with increased baseline temperature allowed discerning between dermatomes with absent, impaired, and normal pinprick sensation when using an objective measure (ie, N2P2 amplitude). In contrast, the pain perception to contact heat stimulation was independent of pinprick scores. Conclusion Applying pinprick testing is of limited sensitivity to assess spinothalamic tract function in spinal cord disorders. The application of CHEPs (using standard and increased baseline temperatures) as an objective readout provides complementary information of spinothalamic tract functional integrity beyond pinprick testing.

Enhancing K-Cl co-transport restores normal spinothalamic sensory coding in a neuropathic pain model.

Neuropathic pain is a widespread and highly debilitating condition commonly resulting from injury to the nervous system, one main sequela of which is tactile allodynia, a pain induced by innocuous mechanical stimulation of the skin. Yet, the cellular mechanisms and neuronal substrates underlying this pathology have remained elusive. We studied this by quantifying and manipulating behavioural and neuronal nociceptive thresholds in normal and pathological pain conditions. We found that, in both control rats and those with pain hypersensitivity induced by nerve injury, the nociceptive paw withdrawal threshold matches the response threshold of nociceptive-specific deep spinothalamic tract neurons. In contrast, wide dynamic range or multimodal spinothalamic tract neurons showed no such correlation nor any change in properties after nerve injury. Disrupting Cl(-) homeostasis by blocking K(+)-Cl(-) co-transporter 2 replicated the decrease in threshold of nociceptive-specific spinothalamic tract neurons without affecting wide dynamic range spinothalamic tract cells. Accordingly, only combined blockade of both GABAA- and glycine-gated Cl(-) channels replicated the effects of nerve injury or K(+)-Cl(-) co-transporter 2 blockade to their full extent. Conversely, rescuing K(+)-Cl(-) co-transporter 2 function restored the threshold of nociceptive-specific spinothalamic tract neurons to normal values in animals with nerve injury. Thus, we unveil a tight association between tactile allodynia and abnormal sensory coding within the normally nociceptive-specific spinothalamic tract. Thus allodynia appears to result from a switch in modality specificity within normally nociceptive-specific spinal relay neurons rather than a change in gain within a multimodal ascending tract. Our findings identify a neuronal substrate and a novel cellular mechanism as targets for the treatment of pathological pain.

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.