Post-stroke Pain Research Articles

A Study of Diffusion Tensor Imaging in Central Post-Stroke Pain: Traveling Beyond the Pain Pathways.

Central post-stroke pain (CPSP), seen in the aftermath of a stroke, is an underdiagnosed entity but quite a disabling complication. All the postulated theories regarding the pathogenesis of CPSP point to its origin in the central pain pathways. However, this study attempts to demonstrate the role of other contributing areas in the generation of CPSP. In this single-center tertiary care hospital-based study, 24 patients with both ischemic and hemorrhagic strokes of variable durations were recruited, and Magnetic Resonance Imaging (MRI) imaging with diffusion tensor imaging (DTI) acquisition was done. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the spinothalamic tract (STT), corticospinal tract (CST), superior thalamic radiation (STR), basal ganglia (BG), and primary somatosensory cortex (SSC) were compared between normal and abnormal sides and also in extrathalamic lesions separately. Significant differences with lower FA were noted in STT, CST, STR, and SSC and higher ADC values in BG, STR, CST, and SSC on comparison between the normal and lesion sides. On individual sub-analysis, ischemic stroke had significant changes in the FA value of CST and the ADC value of STR and CST, while hemorrhagic stroke had significant changes in the FA and ADC values of STR and SSC, as well as the FA value of STT. In the analysis of the extrathalamic strokes, significance persisted in all the studied parameters except the BG. The CST abnormalities were evident even in patients with clinical motor improvement. On multivariate analysis, visual analogue scale score severity was correlated with thalamic lesions. Contrary to the belief that STT is solely responsible for CPSP, the role of CST, STR, BG, and SSC as contributing areas is evident from this study and may be more well established if studied in a larger population.

Post-Stroke Neuropsychiatric Complications: Types, Pathogenesis, and Therapeutic Intervention.

Almost all stroke survivors suffer physical disabilities and neuropsychiatric disturbances, which can be briefly divided into post-stroke neurological diseases and post-stroke psychiatric disorders. The former type mainly includes post-stroke pain, post-stroke epilepsy, and post-stroke dementia while the latter one includes post-stroke depression, post-stroke anxiety, post-stroke apathy and post-stroke fatigue. Multiple risk factors are related to these post-stroke neuropsychiatric complications, such as age, gender, lifestyle, stroke type, medication, lesion location, and comorbidities. Recent studies have revealed several critical mechanisms underlying these complications, namely inflammatory response, dysregulation of the hypothalamic pituitary adrenal axis, cholinergic dysfunction, reduced level of 5-hydroxytryptamine, glutamate-mediated excitotoxicity and mitochondrial dysfunction. Moreover, clinical efforts have successfully given birth to many practical pharmaceutic strategies, such as anti-inflammatory medications, acetylcholinesterase inhibitors, and selective serotonin reuptake inhibitors, as well as diverse rehabilitative modalities to help patients physically and mentally. However, the efficacy of these interventions is still under debate. Further investigations into these post-stroke neuropsychiatric complications, from both basic and clinical perspectives, are urgent for the development of effective treatment strategies.

Frequency of Central Post-Stroke Pain and Its Impact on Quality of Life

Objective: This study aims to determine the frequency of central post-stroke pain (CPSP) in a patient population with stroke as well as investigating the relationship between CPSP and patients' clinical/demographic characteristics, pain intensity, functional status, and quality of life.
 Methods: The study included 150 patients, who had a stroke and were aged 18 years and above. Demographic data of the patients, time since onset, and etiology, localization of the cerebral lesion, affected side, ambulation status, and Brunnstrom stages were recorded. Douleur neuropathique 4 questions (DN4) were used to assess the presence of CPSP. Visual Analog Scale (VAS) was used for pain intensity, functional ambulation scale (FAS) was used for ambulation status, Barthel Index (BI) was used for functional status, and the stroke impact scale (SIS) was used for quality of life.
 Results: The mean age of the patients was 67±11.5 years, 54.7% was male, and 45.3% was female. CPSP was evaluated in 15.3% of patients. There was no significant difference between the affected side of the body and age, gender, time since onset, BI scores, and ambulation status of patients according to their CPSP status (p>0.05). There was no statistically significant difference between SIS sub-parameter scores and the presence of CPSP (p>0.05). In correlation analysis, a significant relationship was found between Barthel Indexes and all SIS domains except memory and emotion (p

Factors influencing recovery of upper limb motor function during constraint-induced movement therapy for people with stroke.

The aim of this study is to determine the personal and clinical factors that can predict recovery of motor function in people with stroke. Characteristics of the study participants such as age, sex, time since stroke and type of stroke, motor function, shoulder pain, amount and quality of use of the affected limb in the real world, wrist and elbow spasticity, handedness, central post-stroke pain and dose of massed practice were recorded. The data obtained were analyzed using descriptive statistics and multiple regression. A total of 144 patients with stroke with mean age, 58.71 ± 19.90 years participated in the study. The result showed that, the whole model significantly explained the total variance by 88.4%, F(14, 144) = 32.870, R 2 = 0. 0.781, p < 0.001. However, in the final model, only four independent variables in the order of degree of predictability, amount of use of the limb in the real world (Beta = 0.455, p = 0.003), intensity of practice during rehabilitation session (Beta = 0.321, p < 0.001), wrist spasticity (Beta = 0.148, p = 0.004) and side affected (Beta = 0.093, p = 0.033) significantly predicted recovery of motor function. Encouraging the use of the limb in the real world may be more important than practice during rehabilitation session in the clinic or in the laboratory.

The effect and mechanism of exercise for post-stroke pain.

One of the common negative effects of a stroke that seriously lowers patients' quality of life is post-stroke pain (PSP). Thus, exercise in PSP management has become a hot research topic. The main advantages of exercise therapy are affordability and ease of acceptance by patients compared to other treatment methods. Therefore, this article reviews the effectiveness and possible mechanisms of exercise interventions for PSP. Exercise training for patients with PSP not only improves physical function but also effectively reduces pain intensity and attenuates the behavioral response to pain. In addition, exercise therapy can improve brain function and modulate levels of pro-inflammatory and neurotrophic factors to exert specific analgesic effects. Potential mechanisms for exercise intervention include modulation of synaptic plasticity in the anterior cingulate gyrus, modulation of endogenous opioids in vivo, reversal of brain-derived neurotrophic factor overexpression, inhibition of purinergic receptor (P2X4R, P2X7R) expression, and inhibition of microglia activation. However, current research on exercise for PSP remains limited, and the sustainable benefits of exercise interventions for PSP need to be further investigated.

Chronic Pain Considerations in Patients with Cardiovascular Disease.

Cardiovascular disease affects close to half of the United States population and many of these patients will develop chronic pain syndromes as a result of their disease process. This article provides an overview of several pain syndromes that result, directly or indirectly, from cardiovascular disease including peripheral arterial disease, angina, thoracic outlet syndrome, postamputation pain, complex regional pain syndrome, and poststroke pain. Psychological and medical comorbidities that affect the medical decision-making process in the treatment of chronic pain associated with cardiovascular disease are also discussed.

Post Hoc Subgroup Analysis of the BCause Study Assessing the Effect of AbobotulinumtoxinA on Post-Stroke Shoulder Pain in Adults.

Botulinum toxin type A is approved for the focal treatment of spasticity; however, the effectiveness of abobotulinumtoxinA (aboBoNT-A) in patients with shoulder pain who have set reduced pain as a treatment goal is understudied. In addition, some patients encounter delays in accessing treatment programs; therefore, the suitability of aboBoNT-A for pain reduction in this population requires investigation. These factors were assessed in aboBoNT-A-naive Brazilian patients in a post hoc analysis of data from BCause, an observational, multicenter, prospective study (NCT02390206). Patients (N = 49, n = 25 female; mean (standard deviation) age of 60.3 (9.1) years; median (range) time since onset of spasticity of 16.1 (0-193) months) received aboBoNT-A injections to shoulder muscles in one or two treatment cycles (n = 47). Using goal attainment scaling (GAS), most patients achieved their goal of shoulder pain reduction after one treatment cycle (72.1%; 95% confidence interval: 57.2-83.4%). Improvements in GAS T-score from baseline, clinically meaningful reductions in pain score at movement, and clinically meaningful increases in passive shoulder abduction angle further improved with repeated treatment more than 4 months later, despite treatment starting at a median of 16.1 months after the onset of spasticity. These findings support the further investigation of aboBoNT-A injections in chronic post-stroke shoulder pain.

Tuina for shoulder pain after stroke: A protocol for systematic review and meta-analysis.

Post-stroke shoulder pain is a relatively common complication in stroke patients, with an incidence of 16% to 84% and poor outcomes with anti-inflammatory or sedative medications. This study will evaluate the results of a randomized controlled trial to determine the effectiveness and safety of Tuina in the treatment of post-stroke shoulder pain. The Chinese and English search strategies were used to search China National Knowledge Infrastructure, Chinese Scientific Journal Database, Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, PubMed, Wanfang Database, and Web of Science were used to search seven databases. All eligible studies published on or before September 15, 2022, will be selected. To improve the validity of this study, only clinical randomized controlled trials related to the use of Tuina for post-stroke shoulder pain will be included. The screening will be performed by 2 independent reviewers and data synthesis, bias analysis, subgroup analysis, and meta-analysis will be performed using RevMan (V.5.4) software. The study will provide a high-quality evaluation of the effectiveness and safety of Tuina in the treatment of post-stroke shoulder pain. This systematic review will provide evidence to determine whether Tuina is an effective and safe intervention for treating patients with post-stroke shoulder pain.PROSPERO registration number: CRD42022360401.

Peripheral Nerve Stimulation in Painful Conditions of the Upper Extremity-An Overview.

Our objective is to present a brief history of the evolution of peripheral nerve stimulation, the current understanding of peripheral nerve stimulation mechanisms in chronic pain, peripheral nerve stimulation applications in upper extremity chronic pain conditions, and complications of peripheral nerve stimulation. The evolution of peripheral nerve stimulation from the early ages to the current status has been facilitated by discoveries in neurobehavioral mechanisms of pain, advances in technology and percutaneous lead development, and the availability of high-quality portable ultrasound units. Peripheral nerve stimulation application in managing upper extremity pain of amputated limbs, post-stroke shoulder pain, complex regional pain syndrome (CRPS), and median, ulnar, and radial neuropathies are discussed. Finally, we describe complications of peripheral nerve stimulation. The availability of ultrasound-guided peripheral nerve stimulation techniques and superior peripheral nerve stimulation technology have opened up new and minimally invasive treatment options for chronic intractable neuropathic pain of the upper extremity. Additionally, the ability to place peripheral nerve stimulation leads percutaneously without open peripheral nerve surgery expands the pool of implanting physicians, while simultaneously decreasing the risks and complications that are associated with open surgery.

Deep Brain Stimulation of the Central Lateral and Ventral Posterior Thalamus for Central Poststroke Pain Syndrome: Preliminary Experience

ObjectiveThe beneficial effects of thalamic deep brain stimulation (DBS) at various target sites in treating chronic central neuropathic pain (CPSP) remain unclear. This study aimed to evaluate the effectiveness of DBS at a previously untested target site in the central lateral (CL) thalamus, together with classical sensory thalamic stimulation (ventral posterior [VP] complex). Materials and MethodsWe performed a monocentric retrospective study of a consecutive series of six patients with CPSP who underwent combined DBS lead implantation of the CL and VP. Patient-reported outcome measures were recorded before and after surgery using the numeric rating scale (NRS), short-form McGill pain questionnaire (sf-MPQ), EuroQol 5-D quality-of-life questionnaire, and Beck Depression Inventory. DBS leads were reconstructed and projected onto a three-dimensional stereotactic atlas. ResultsNRS—but not sf-MPQ–rated pain intensity—was significantly reduced throughout the follow-up period of 12 months compared with baseline (p = 0.005, and p = 0.06 respectively, Friedman test). At the last available follow-up (12 to 30 months), three patients described a more than 50% reduction. Two of the three long-term responders were stimulated in the CL (1000 Hz, 90 μs, 3.5–5.0 mA), whereas the third preferred VP complex stimulation (50 Hz, 200 μs, 0.7–1.2 mA). No persistent procedure- or stimulation-associated side effects were noted. ConclusionsThese preliminary findings suggest that DBS of the CL might constitute a promising alternative target in cases in which classical VP complex stimulation does not yield satisfactory postoperative pain reduction. The results need to be confirmed in larger, prospective series of patients.

Efficacy and safety of different antidepressants and anticonvulsants in central poststroke pain: A network meta-analysis and systematic review.

To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice. PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis. A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline. All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.

Post-Stroke Complex Regional Pain Syndrome and Upper Limb Inactivity in Hemiplegic Patients: A Cross-Sectional Study.

PurposeThe purpose of this study was to investigate the prevalence of post-stroke complex regional pain syndrome (CRPS) and to examine the characteristics of inactivity status of the upper limb in post-stroke CRPS patients. In addition, as a sub-analysis, the association between the upper limb inactivity status and pain intensity was investigated in post-stroke CRPS patients.Patients and MethodsThis cross-sectional study included 102 patients with first-ever stroke between April 2019 and February 2020. Each patient was allocated into one of two groups based on the presence or absence of CRPS. Demographic data (age, sex, stroke etiology, lesion side, and number of days since stroke onset) were collected. The following evaluations were performed in all patients: Fugl–Meyer Assessment (FMA), Action Research Arm Test (ARAT), and Motor Activity Log (MAL). The numerical rating scale (NRS) to determine pain intensity was assessed only in patients with post-stroke CRPS.ResultsNineteen and 83 patients were assigned to the post-stroke CRPS and control group, respectively. The prevalence of post-stroke CRPS was 18.6% (19/102). FMA, ARAT, and MAL scores were significantly lower in patients with post-stroke CRPS than those without it. FMA and ARAT scores were significantly correlated with NRS scores, but MAL was almost zero-scored in patients with post-stroke CRPS.ConclusionThe study results indicated that activity status of the affected upper limb was severely deteriorated, and more inactivity of the upper limb was associated with higher pain intensity in patients with post-stroke CRPS. Thus, our results suggest that post-stroke CRPS may be influenced by the degree of upper limb inactivity after stroke.

PO159 / #731 MOTOR CORTEX STIMULATION THAT WAS EFFECTIVE FOR 20 YEARS FOR TYPE 2 CRPS WITH HEMIBODY INVOLVEMENT: THE NEED TO REORGANIZE NEW INDICATIONS: E-POSTER VIEWING

Motor cortex stimulation (MCS) has been suggested as a last option for central and peripheral neuropathic pain, but its long-term effectiveness has not been demonstrated, so it is not currently accepted as a pain treatment. So, we need to find new real indications, except for existing indications such as central poststroke pain (CPSP). In this regard, the author would like to report a case in which the effect was clear until 20 years after MCS implantation in 2000.

PO135 / #716 DORSAL ROOT GANGLION STIMULATION FOR TREATMENT OF CENTRAL POST-STROKE PAIN IN THE LOWER EXTREMITY - REPORT OF TWO CASES AND PATHOPHYSIOLOGICAL BACKGROUND: E-POSTER VIEWING

Pain following stroke is a common complication that is poorly understood. It can be easily overlooked due to its variable characteristics, concurrent comorbid medical issues, and impairments in cognition or communication. While pain can create its own disabilities secondary to a decrease in function, its effect on post-stroke recovery of patients can substantially impact their future quality of life by preventing optimal participation and gains during rehabilitation. Indeed, as is the case with many other chronic pain syndromes, central post-stroke pain (CPSP) is often refractory or responds poorly to medication and other treatments.

PO128 / #1012 COMBINED MOTOR CORTEX AND SPINAL CORD STIMULATION IN CHRONIC POST-STROKE PAIN AND NEUROPATHIC PAIN: E-POSTER VIEWING

Management of central post-stroke pain (CPSP), remains a challenging issue. When combined with other forms of neuropathic pain, it even imposes a bigger challenge. Several options from Deep Brain Stimulation to Motor cortex Stimulation (MCS) have been used with variable outcomes.

Repetitive transcranial magnetic stimulation of the primary motor cortex in stroke survivors-more than motor rehabilitation: A mini-review.

Stroke is a leading cause of morbidity and mortality among elderly populations worldwide. During the early phase of stroke, restoring blood circulation is of utmost importance to protect neurons from further injury. Once the initial condition is stabilized, various rehabilitation techniques can be applied to help stroke survivors gradually regain their affected functions. Among these techniques, transcranial magnetic stimulation (TMS) has emerged as a novel method to assess and modulate cortical excitability non-invasively and aid stroke survivors in the rehabilitation process. Different cortical regions have been targeted using TMS based on the underlying pathology and distorted function. Despite the lack of a standard operational procedure, repetitive TMS (rTMS) of the primary motor cortex (M1) is considered a promising intervention for post-stroke motor rehabilitation. However, apart from the motor response, mounting evidence suggests that M1 stimulation can be employed to treat other symptoms such as dysphagia, speech impairments, central post-stroke pain, depression, and cognitive dysfunction. In this mini-review, we summarize the therapeutic uses of rTMS stimulation over M1 in stroke survivors and discuss the potential mechanistic rationale behind it.

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits.

To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. Ninety C57BL/6 mice underwent sham (n=36) or transient middle cerebral artery occlusion (tMCAO) (n=54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p&amp;lt; 0.05; gadopentetate, p&amp;lt; 0.001) and 28 p. i of gadopentetate. (p&amp;lt; 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p&amp;gt; 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p&amp;lt; 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0g) and statistically significant in both paws (right and left) with gadopentetate only (p&amp;lt; 0.05). Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

Biological Mechanism on SIRT1/NLRP3/IL-18 Signaling Pathway of Acupuncture for Treatment of Ischemic Stroke with Center Poststroke Pain.

Objective To evaluate the effect of acupuncture on an animal model of ischemic stroke with central poststroke pain (CPSP) through Sirtuin 1 (SIRT1)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/interleukin-18 (IL-18) signaling pathway. Methods Data mining was performed with R package “edgeR,” “limma,” “pathview,” etc., from NCBI Gene Expression Omnibus (GEO) database. Sprague Dawley (SD) rats were divided into 4 groups: sham operation group (Sham group, n = 5), poststroke central pain group (CPSP group, n = 5), poststroke central pain + acupuncture group (AP group, n = 5), central pain after stroke + acupuncture + SIRT1 inhibitor EX527 group (EX527 group, n = 5). Pain behavior testing was performed to determine the mechanical withdrawal threshold (MWT). Quantitative real-time PCR (qRT-PCR) was performed to verify the data mining results from the GEO database. Results The KEGG key pathway map was created using the R package “pathview” package, demonstrating that the expression levels of NLRP3's downstream inflammatory factors IL-18 were downregulated in both of siSIRT1 group compared to the control group and the NLRP3 reconstituted group compared to NLRP3 KO group. QRT-PCR results on animal models of CPSP ischemic stroke showed that the expression levels of SIRT1 were downregulated, the activation of the NLRP3 inflammasome was upregulated, and the expression levels of IL-18 were upregulated in the brain tissues of the surrounding area of the injury. As the pain threshold of CPSP rats was increased, the expression level of S1RT1 was upregulated, and the activation of NLRP3 inflammasome was downregulated. The expression level of IL-18 was downregulated after acupuncture treatment. Conclusion Acupuncture may inhibit CPSP in an animal model of ischemic stroke by upregulating SIRT1 expression levels, inhibition of the activation of the inflammasome, and downregulating IL-18 expression levels.

Pharmacotherapies for Central Post-Stroke Pain: A Systematic Review and Network Meta-Analysis.

Background Central post-stroke pain (CPSP) is a common condition. Several pharmacotherapies have been applied in practice. However, the comparative effectiveness among these pharmacotherapies is unknown. Aim The aim of this study is to study the comparative effectiveness among differential pharmacotherapies for CPSP through a network meta-analysis. Methods We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science from inception to 30 March 2022, without any language restriction. Two reviewers independently screened the retrieved articles, extracted data, and evaluated the risk of bias (RoB). The outcome of interest of the study was the change in the scores of pain intensity scales. We estimated standard mean differences (SMDs) between treatments and calculated corresponding 95% CIs. Results Thirteen randomized controlled trials (529 participants) were included after a screen of 1774 articles. Compared with placebo, pamidronate (SMD -2.43, 95% CI -3.54 to -1.31; P − score = 0.93), prednisone (SMD -2.38, 95% CI -3.09 to -1.67; P − score = 0.92), levetiracetam (SMD -2.11, 95% CI -2.97 to -1.26; P − score = 0.87), lamotrigine (SMD -1.39, 95% CI -2.21 to -0.58; P − score = 0.73), etanercept (SMD -0.92, 95% CI -1.8 to -0.03; P − score = 0.59), and pregabalin (SMD -0.46, 95% CI -0.71 to -0.22; P − score = 0.41) had significantly better treatment effect. Pamidronate, prednisone, and levetiracetam ranked as the first three most effective treatments. In subgroup analyses, prednisone, levetiracetam, lamotrigine, and pregabalin were more effective than placebo as oral pharmacotherapies, while etanercept was more effective than placebo as injectable pharmacotherapy. Conclusions Our study confirmed that pamidronate, prednisone, and guideline-recommended anticonvulsants were effective for reducing pain intensity for CPSP. Pamidronate and prednisone showed better effect than other pharmacotherapies, which warrants further investigation.

Network Effects of Brain Lesions Causing Central Poststroke Pain.

This study was undertaken to test whether lesions causing central poststroke pain (CPSP) are associated with a specific connectivity profile, whether these connections are associated with metabolic changes, and whether this network aligns with neuromodulation targets for pain. Two independent lesion datasets were utilized: (1) subcortical lesions from published case reports and (2) thalamic lesions with metabolic imaging using 18F- fluorodeoxyglucose positron emission tomography-computed tomography. Functional connectivity between each lesion location and the rest of the brain was assessed using a normative connectome (n=1,000), and connections specific to CPSP were identified. Metabolic changes specific to CPSP were also identified and related to differences in lesion connectivity. Therapeutic relevance of the network was explored by testing for alignment with existing brain stimulation data and by prospectively targeting the network with repetitive transcranial magnetic stimulation (rTMS) in 7 patients with CPSP. Lesion locations causing CPSP showed a specific pattern of brain connectivity that was consistent across two independent lesion datasets (spatial r= 0.82, p< 0.0001). Connectivity differences were correlated with postlesion metabolism (r= -0.48, p< 0.001). The topography of this lesion-based pain network aligned with variability in pain improvement across 12 prior neuromodulation targets and across 32 patients who received rTMS to primary motor cortex (p< 0.05). Prospectively targeting this network with rTMS improved CPSP in 6 of 7 patients. Lesions causing pain are connected to a specific brain network that shows metabolic abnormalities and promise as a neuromodulation target. ANN NEUROL 2022;92:834-845.