ArticlePain2009
Role of substance P signaling in enhanced nociceptive sensitization and local cytokine production after incision.
Article in Pain, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 121 citations in OpenAlex.
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- Dissecting bi-directional neuroimmune crosstalk in an in vitro model relevant to apical periodontitis.Scientific reports · 2026Article
- An attention-demanding hunting paradigm engages the superior colliculus-zona incerta circuit mediating analgesia in male mice.Nature communications · 2026Article
- Effects of photobiomodulation on nociceptor activity and the expression of proinflammatory cytokines after temporomandibular joint disc injury in rats.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2026Article
- The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.Biomedicines · 2025Review
- Specific Activation of Dopamine Receptor D1 Expressing Neurons in the PrL Alleviates CSDS-Induced Anxiety-Like Behavior Comorbidity with Postoperative Hyperalgesia in Male Mice.Molecular neurobiology · 2025Article
- Topical neurokinin-1 receptor antagonism ameliorates ocular pain and prevents corneal nerve degeneration in an animal model of dry eye disease.Pain reports · 2025Article
- Article
- Chronic Postsurgical Pain in Children and Adolescents: A Call for Action.Journal of pain research · 2024Review
- Maternal high-fat diet increases airway sensory innervation and reflex bronchoconstriction in adult offspring.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Mast cell-derived BH4 is a critical mediator of postoperative pain.bioRxiv : the preprint server for biology · 2023Article
- Phase-specific differential regulation of mechanical allodynia in a murine model of neuropathic pain by progesterone.Frontiers in pharmacology · 2023Article
- Intraoperative abobotulinumtoxinA alleviates pain after surgery and improves general wellness in a translational animal model.Scientific reports · 2022Article
- A compendium of validated pain genes.WIREs mechanisms of disease · 2022Review
- Insulin increases sensory nerve density and reflex bronchoconstriction in obese mice.JCI insight · 2022Article
- Electroacupuncture relieves hyperalgesia by regulating neuronal-glial interaction and glutamate transporters of spinal dorsal horns in rats with acute incisional neck pain.Frontiers in neuroscience · 2022Article
- Role of leukotriene B4 (LTB4)-LTB4 receptor 1 signaling in post-incisional nociceptive sensitization and local inflammation in mice.PloS one · 2022Article
- Atypical presentation of complex regional pain syndrome: neuropathic itching - A case report.Anesthesia and pain medicine · 2021Article
- NGF-Induced Nav1.7 Upregulation Contributes to Chronic Post-surgical Pain by Activating SGK1-Dependent Nedd4-2 Phosphorylation.Molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Substance P (SP) signaling facilitates nociceptive sensitization in various inflammatory and chronic pain models and we postulated that SP signaling might also contribute to the development of post-incisional hyperalgesia. These studies used mice with a deletion of the pre-protachykinin A gene (ppt-A(-/-)) which codes for SP to determine the role of SP signaling in post-incisional pain and in the increased cytokine and nerve growth factor (NGF) expression observed in the incised skin. SP deficient ppt-A(-/-) mice displayed reduced mechanical allodynia and heat hyperalgesia compared to the wild-type (wt) mice at all post-incision time points, despite similar baseline values (p<0.001). Furthermore, the NK-1 receptor antagonist LY303870 attenuated mechanical allodynia produced by incision in the wt mice (p<0.001). Incision also up-regulated IL-6, TNF-alpha and KC levels but not IL-1beta after 2h in the wt mice skin. However, ppt-A(-/-) mice had more skin NGF levels 2h post-incision. Subcutaneous hind paw SP injection produced acute and transient elevations of IL-1beta, IL-6, and KC but modest elevations in TNF-alpha levels in the wt mice. Systemic LY303870 reversed the SP-induced elevations of these cytokines. Hind paw injection of IL-6 and NGF dose dependently produced less mechanical allodynia in the ppt-A(-/-) compared to wt mice. Additionally, SP produced mechanical allodynia in a dose-dependent fashion in wt mice. Therefore, SP supports nociceptive sensitization after hind paw incision and potentially participates directly in modulating the intensity of inflammatory response in peri-incisional tissue.
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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.