Symptom-based pharmacotherapy for neuropathic pain related to spinal disorders: results from a patient-based assessment

Nakajima, Hideaki; Watanabe, Shuji; Honjoh, Kazuya; Kubota, Arisa; Matsumine, Akihiko

doi:10.1038/s41598-022-11345-y

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…A randomized, double-blind, placebo-controlled, phase 3 study found mirogabalin to be a promising treatment for patients with SCI-induced neuropathic pain [71]. Another study suggested that mirogabalin was the most effective treatment for paresthesia/dysesthesia; nevertheless, regarding its treatment efficacy, paresthesia/dysesthesia was the most difficult to relieve pain compared with other types of neurological pain [72].…”

Section: Neuropathic Pain After Spinal Cord Injurymentioning

confidence: 99%

Management of Cervical Spinal Cord Injury without Major Bone Injury in Adults

Nakajima,

Honjoh,

Watanabe

et al. 2023

JCM

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The incidence of cervical spinal cord injury (CSCI) without major bone injury is increasing, possibly because older people typically have pre-existing cervical spinal canal stenosis. The demographics, neurological injury, treatment, and prognosis of this type of CSCI differ from those of CSCI with bone or central cord injury. Spine surgeons worldwide are debating on the optimal management of CSCI without major bone injury. Therefore, this narrative review aimed to address unresolved clinical questions related to CSCI without major bone injury and discuss treatment strategies based on current findings. The greatest divide among spine surgeons worldwide hinges on whether surgery is necessary for patients with CSCI without major bone injury. Certain studies have recommended early surgery within 24 h after injury; however, evidence regarding its superiority over conservative treatment remains limited. Delayed MRI may be beneficial; nevertheless, reliable factors and imaging findings that predict functional prognosis during the acute phase and ascertain the necessity of surgery should be identified to determine whether surgery/early surgery is better than conservative therapy/delayed surgery. Quality-of-life assessments, including neuropathic pain, spasticity, manual dexterity, and motor function, should be performed to examine the superiority of surgery/early surgery to conservative therapy/delayed surgery.

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Section: Neuropathic Pain After Spinal Cord Injurymentioning

confidence: 99%

Management of Cervical Spinal Cord Injury without Major Bone Injury in Adults

Nakajima,

Honjoh,

Watanabe

et al. 2023

JCM

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“…Using these ROIs, the SUV ratio (SUVR) was calculated as SUV max for cervical spinal cord lesions with increased MRI signal intensity in the sagittal plane/SUV mean for the normal cervical spinal cord at the C7/T1 level [27]. The Neuropathic Pain System Inventory (NPSI) was used at the time of (R)-[ 11 C]PK11195 PET/MRI to assess the degree of NeP [28,29]. Each patient gave written informed consent prior to the study.…”

Section: (R)-[ 11 C]pk11195 Pet Imaging In the Rat Spinal Cord Injury...mentioning

confidence: 99%

Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders

Kitade

Nakajima

Tsujikawa

et al. 2022

JCM

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Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[3H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[11C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[11C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP.

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Could Unfold Protein Response Pathway Proteins be a Missing Link in Neuropathic Pain and Alzheimer’s Disease Etiology? — Findings from Computational Studies

Ameenudeen,

Hemalatha

2023

J. Comput. Biophys. Chem.

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Background: Neurodegenerative diseases, including Alzheimer’s disease, are characterized by progressive neuronal cell loss and nervous system damage. Neuropathic pain, resulting from traumatic injury to sensory nerves, is closely associated with these neurodegenerative conditions. Endoplasmic reticulum (ER) stress, arising from protein misfolding or accumulation of unfolded proteins, plays a crucial role in maintaining cellular homeostasis through the activation of the unfolded protein response (UPR). Interestingly, the ER stress pathway has emerged as a potential link between neuropathic pain and Alzheimer’s disease. To investigate this link, we selected specific drugs with known mechanisms of action: GSK2606414, an EIF-2[Formula: see text] phosphorylation inhibitor, Valsartan, which down-regulates ER stress-related proteins, Gemigliptin, known to decrease GRP78 expression, and Melatonin, shown to reduce ATF6 mRNA and protein levels. Additionally, Vemurafenib and Obatoclax were chosen as kinase and Bcl2 inhibitors, respectively. Drug selection was based on data from DrugBank and literature, with their structures obtained from the PubChem database. Main methodologies: Our research aims to identify potential therapeutic targets bridging neuropathic pain and Alzheimer’s disease. Using AutoDock v4.2.6, we conducted molecular docking studies, revealing promising drug–target interactions. We further performed molecular dynamic (MD) simulations for 100 ns using the WEBGRO online server to assess drug-target stability. Additionally, we employed Lipinski screening via the SwissADME web server, assessing pharmacokinetic properties and toxicity. Results: Except for ATF4 (with Metformin), all targets showed favorable affinity toward Obatoclax, with binding energies ranging from −5.32 to −7.48 kcal/mol. The XBP1–Obatoclax complex stability is evaluated using MD simulation. The ADMET screening results indicated that the drugs displayed good intestinal absorption (above 30%), making them suitable for oral administration. Importantly, these drugs showed no inhibitory effects against CYP2D6 isozymes expressed in the CNS. Future perspective: Our in silico findings provide valuable evidence and potential leads for further evaluation and confirmation through in vitro research. The data generated from this study may contribute to the development of novel therapeutics targeting both neuropathic pain and Alzheimer’s disease, offering new hope for patients suffering from these debilitating conditions.

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Symptom-based pharmacotherapy for neuropathic pain related to spinal disorders: results from a patient-based assessment

Cited by 4 publications

References 45 publications

Management of Cervical Spinal Cord Injury without Major Bone Injury in Adults

Management of Cervical Spinal Cord Injury without Major Bone Injury in Adults

Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders

Could Unfold Protein Response Pathway Proteins be a Missing Link in Neuropathic Pain and Alzheimer’s Disease Etiology? — Findings from Computational Studies

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