ArticlePain2012
Increasing TNF levels solely in the rat hippocampus produces persistent pain-like symptoms.
Article in Pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- From localized to long-range: functional connectivity alterations in mild to moderate chronic low back pain patients.Quantitative imaging in medicine and surgery · 2026Article
- The role of sesamin in alleviating acute and chronic pain: a focus on the TRL4-NF-KB-NLRP3 signaling pathway.Molecular biology reports · 2025Article
- Olfactory bulbectomy induces nociceptive alterations associated with gliosis in male rats.IBRO neuroscience reports · 2023Article
- Increased hippocampal efficiency is associated with greater headache frequency in adolescents with chronic headache.Cerebral cortex communications · 2023Article
- [Hippocampus is involved in 17β-estradiol exacerbating experimental occlusal inter- ference-induced chronic masseter hyperalgesia in ovariectomized rats].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2022Article
- Selective inhibition of soluble TNF using XPro1595 relieves pain and attenuates cerulein-induced pathology in mice.BMC gastroenterology · 2021Article
- Underweight and obesity are strong predictors of clinical outcomes in patients with ankylosing spondylitis: data from the Smart-phone SpondyloArthritis Management System.Therapeutic advances in musculoskeletal disease · 2021Article
- The α7 nicotinic acetylcholine receptor positive allosteric modulator prevents lipopolysaccharide-induced allodynia, hyperalgesia and TNF-α in the hippocampus in mice.Pharmacological reports : PR · 2019Article
- Environmental enrichment improves pain sensitivity, depression-like phenotype, and memory deficit in mice with neuropathic pain: role of NPAS4.Psychopharmacology · 2019Article
- An integrated review on new targets in the treatment of neuropathic pain.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Review
- Chemokine receptor CCR2 contributes to neuropathic pain and the associated depression via increasing NR2B-mediated currents in both D1 and D2 dopamine receptor-containing medium spiny neurons in the nucleus accumbens shell.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- The Chinese Medicine Wu-Tou Decoction Relieves Neuropathic Pain by Inhibiting Hippocampal Microglia Activation.Scientific reports · 2018Article
- Forebrain medial septum sustains experimental neuropathic pain.Scientific reports · 2018Article
- ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological, and sleep-related factors following an acute low back pain episode-the good, the bad, and the ugly.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2018Article
- Cannabinoids and agmatine as potential therapeutic alternatives for cisplatin-induced peripheral neuropathy.Journal of experimental pharmacology · 2018Review
- Evidence that CA3 is Underling the Comorbidity Between Pain and Depression and the Co-curation by Wu-Tou decoction in Neuropathic Pain.Scientific reports · 2017Article
- Resilience and Vulnerability to Pain and Inflammation in the Hippocampus.International journal of molecular sciences · 2017Review
- Article
- Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain.Molecular pain · 2016Article
- Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The manifestation of chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). Previously, we have shown that the hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation. Using an animal model of peripheral neuropathic pain, we have demonstrated that intracerebroventricular infusion of a TNF antibody adjacent to the hippocampus completely alleviated pain. Furthermore, intracerebroventricular infusion of rTNF adjacent to the hippocampus induced pain behavior in naïve animals similar to that expressed during a model of neuropathic pain. These data support our premise that enhanced production of hippocampal-TNF is integral in pain sensation. In the present study, TNF gene expression was induced exclusively in the hippocampus, eliciting increased local bioactive TNF levels, and animals were assessed for pain behaviors. Male Sprague-Dawley rats received stereotaxic injection of gold nanorod (GNR)-complexed cDNA (control or TNF) plasmids (nanoplasmidexes), and pain responses (i.e., thermal hyperalgesia and mechanical allodynia) were measured. Animals receiving hippocampal microinjection of TNF nanoplasmidexes developed thermal hyperalgesia bilaterally. Sensitivity to mechanical stimulation also developed bilaterally in the rat hind paws. In support of these behavioral findings, immunoreactive staining for TNF, bioactive levels of TNF, and levels of TNF mRNA per polymerase chain reaction analysis were assessed in several brain regions and found to be increased only in the hippocampus. These findings indicate that the specific elevation of TNF in the hippocampus is not a consequence of pain, but in fact induces these behaviors/symptoms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.