Mast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice

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dc.contributor.authorMeloto, Carolina B.
dc.contributor.authorIngelmo, Pablo
dc.contributor.authorPerez, Eduardo Vega
dc.contributor.authorPitt, Rebecca
dc.contributor.authorGonzalez Cardenas, Victor Hugo
dc.contributor.authorMohamed, Nada
dc.contributor.authorSotocinal, Susana G.
dc.contributor.authorBourassa, Valerie
dc.contributor.authorLima, Lucas Vasconcelos
dc.contributor.authorRibeiro-da-Silva, Alfredo
dc.contributor.authorMogil, Jeffrey S.
dc.contributor.authorDiatchenko, Luda
dc.date.accessioned2025-01-20T23:53:48Z
dc.date.available2025-01-20T23:53:48Z
dc.date.issued2021
dc.description.abstractIntroduction: Mast cell (MC) activation could establish a positive feedback loop that perpetuates inflammation and maintains pain. Stabilizing MCs with ketotifen fumarate (KF) may disrupt this loop and relieve pain. Objective: We aimed to test the effect of treatment with KF in pain assays in mice and in a case series of patients with chronic widespread pain. Methods: The analgesic effect of KF was tested in CD-1 mice injected with formalin, complete Freund's adjuvant, or subjected to spared nerve injury. In addition, wild-type (C57BL/6) and MC-deficient (C57BL/6-Kit(W-sh/W-sh)) mice were injected with formalin or complete Freund's adjuvant and treated with KF. Patients with chronic widespread pain (n = 5; age: 13-16 years) who failed to respond to standard of care participated in a 16-week treatment trial with KF (6 mg/d). Ketotifen fumarate's therapeutic effect was evaluated using the patient global impression of change. Results: In the mouse experiments, KF produced dose- and MC-dependent analgesic effects against mechanical allodynia in the acute and chronic inflammatory pain but not neuropathic pain assays. In the patient case series, 4 patients reported that activity limitations, symptoms, emotions, and overall quality of life related to their pain condition were "better" or "a great deal better" since beginning treatment with KF. This was accompanied by improvements in pain comorbid symptoms. Conclusion: Treatment with KF is capable of reducing established inflammatory-induced mechanical nociception in an MC-dependent manner in mice, and it may be beneficial for the treatment of chronic pain conditions.
dc.fuente.origenWOS
dc.identifier.doi10.1097/PR9.0000000000000902
dc.identifier.eissn2471-2531
dc.identifier.urihttps://doi.org/10.1097/PR9.0000000000000902
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94996
dc.identifier.wosidWOS:000711826100003
dc.issue.numero2
dc.language.isoen
dc.revistaPain reports
dc.rightsacceso restringido
dc.subjectMast cells
dc.subjectKetotifen fumarate
dc.subjectMechanical allodynia
dc.subjectInflammatory pain
dc.subjectChronic widespread pain
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleMast cell stabilizer ketotifen fumarate reverses inflammatory but not neuropathic-induced mechanical pain in mice
dc.typeartículo
dc.volumen6
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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