ArticleThe journal of pain2010
Pain intensity and duration can be enhanced by prior challenge: initial evidence suggestive of a role of microglial priming.
Article in The journal of pain, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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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
48 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Progress in Pathological and Therapeutic Research of HIV-Related Neuropathic Pain.Cellular and molecular neurobiology · 2023Pooled it
- Trial
- Review
- Induction of Endometriosis in a Menstruating Mouse Model (Mus musculus): A Translational Animal Disease Model.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Article
- TRPV1 corneal neuralgia mutation: Enhanced pH response, bradykinin sensitization, and capsaicin desensitization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Excitatory and inhibitory neuronal signaling in inflammatory and diabetic neuropathic pain.Molecular medicine (Cambridge, Mass.) · 2023Review
- Comparison of outcome after right colectomy with an enhanced recovery programme in patients with inflammatory bowel disease and patients operated on for other conditions: a monocentric retrospective study.International journal of colorectal disease · 2021Article
- Pain and Cellular Migration Induced byFrontiers in immunology · 2021Article
- Pain in the Developing Brain: Early Life Factors Alter Nociception and Neurobiological Function in Adolescent Rats.Cerebral cortex communications · 2021Article
- Conditional expression of HIV-1 tat in the mouse alters the onset and progression of tonic, inflammatory and neuropathic hypersensitivity in a sex-dependent manner.European journal of pain (London, England) · 2020Article
- Microglia: A Potential Therapeutic Target for Sepsis-Associated Encephalopathy and Sepsis-Associated Chronic Pain.Frontiers in pharmacology · 2020Review
- The Bidirectional Relationship Between Sleep and Inflammation Links Traumatic Brain Injury and Alzheimer's Disease.Frontiers in neuroscience · 2020Review
- Article
- Repeated Morphine Prolongs Postoperative Pain in Male Rats.Anesthesia and analgesia · 2019Article
- Systemic Lipopolysaccharide-Induced Pain Sensitivity and Spinal Inflammation Were Reduced by Minocycline in Neonatal Rats.International journal of molecular sciences · 2018Article
- Neuroinflammation and Central Sensitization in Chronic and Widespread Pain.Anesthesiology · 2018Review
- Psychosocial Stress Delays Recovery of Postoperative Pain Following Incisional Surgery in the Rat.Neuroscience · 2018Article
- Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.Frontiers in physiology · 2018Article
- An Inflammation-Centric View of Neurological Disease: Beyond the Neuron.Frontiers in cellular neuroscience · 2018Review
- Inflammatory 'double hit' model of temporomandibular joint disorder with elevated CCL2, CXCL9, CXCL10, RANTES and behavioural hypersensitivity in TNFR1/R2-/- mice.European journal of pain (London, England) · 2017Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
unlabelledActivation of spinal microglia and consequent release of proinflammatory mediators facilitate pain. Under certain conditions, responses of activated microglia can become enhanced. Enhanced microglial production of proinflammatory products may result from priming (sensitization), similar to macrophage priming. We hypothesized that if spinal microglia were primed by an initial inflammatory challenge, subsequent challenges may create enhanced pain. Here, we used a "two-hit" paradigm using 2 successive challenges, which affect overlapping populations of spinal microglia, presented 2 weeks apart. Mechanical allodynia and/or activation of spinal glia were assessed. Initially, laparotomy preceded systemic lipopolysaccharide (LPS). Prior laparotomy caused prolonged microglial (not astrocyte) activation plus enhanced LPS-induced allodynia. In this "two-hit" paradigm, minocycline, a microglial activation inhibitor, significantly reduced later exaggerated pain induced by prior surgery when minocycline was administered intrathecally for 5 days starting either at the time of surgery or 5 days before LPS administration. To test generality of the priming effect, subcutaneous formalin preceded intrathecal HIV-1 gp120, which activates spinal microglia and causes robust allodynia. Prior formalin enhanced intrathecal gp120-induced allodynia, suggesting that microglial priming is not limited to laparotomy and again supporting a spinal site of action. Therefore, spinal microglial priming may increase vulnerability to pain enhancement. PERSPECTIVE: Spinal microglia may become "primed" (sensitized) following their activation by disparate forms of peripheral trauma/inflammation. As a result, such primed microglia may overrespond to subsequent challenges, thereby enhancing pain intensity and duration.
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