Sex-dependent effects of the targeted nerve growth factor mutation (R100E) on pain behavior, joint inflammation, and bone erosion in mice

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-09-15T00:30:27Z
Fecha de publicación2024-01-01
ResumenAbstract Nerve growth factor (NGF)-R100E is a mutated form of human recombinant NGF that reduces the binding of NGF to its p75NTR receptor while retaining its affinity toward the TrkA receptor. Here, we used human wild type NGF and NGF-R100E knock-in mice to investigate the effects of this NGF mutation on inflammation-induced pain-related behaviors and bone loss. The hNGF-R100E mutation did not alter the nerve fiber density in the sciatic nerve, ankle joint synovium, and skin of naïve mice. Withdrawal responses to mechanical, thermal, and cold stimuli before and after joint inflammation induced by intra-articular injection of complete Freund adjuvant (CFA) were similar between human recombinant nerve growth factor-wild type and hNGF-R100E male and female mice while weight bearing and gait analysis revealed significant differences. Intriguingly, hNGF-R100E male and female mice showed only mild changes, indicating lower degrees of deep joint–related pain compared to their wild type counterparts. Furthermore, micro-CT analysis demonstrated that hNGF-R100E female mice, but not males, were protected from CFA-induced bone loss, and mRNA analysis showed a different gene regulation indicating a sex-dependent relationship between NGF, inflammation, and bone loss. In conclusion, our study reveals that the hNGF-R100E mutation renders mice insensitive to inflammation-induced impact on joint loading and gait while preserving the development of the peripheral nociceptive neurons and sensitivity to punctate stimulation of the skin. Notably, the mutation uncovers a sex-dependent relationship between NGF and inflammation-induced bone loss. These findings offer valuable insights into NGF as a target for pain management and the interplay between NGF and bone architecture.es_ES
Doihttps://doi.org/10.1097/j.pain.0000000000003343es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/2429
Idiomaeses_ES
EditorialOvid Technologies (Wolters Kluwer Health)es_ES
RelaciónPaines_ES
URL relacionadohttps://doi.org/10.1097/j.pain.0000000000003343es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuentePain
TítuloSex-dependent effects of the targeted nerve growth factor mutation (R100E) on pain behavior, joint inflammation, and bone erosion in micees_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorMorado-Urbina, Carlos E.
AutorKato, Jungo
AutorSandor, Katalin
AutorVazquez-Mora, Juan Antonio
AutorMöller, Kristina Ängeby
AutorSimon, Nils
AutorSalcido, Jaira
AutorMartinez-Martinez, Arisai
AutorMunoz-Islas, Enriqueta
AutorJimenez-Andrade, Juan Miguel
AutorSvensson, Camilla I.
AutorMorado-Urbina, Carlos E.es_ES
AutorKato, Jungoes_ES
AutorSandor, Katalines_ES
AutorVazquez-Mora, Juan Antonioes_ES
AutorMöller, Kristina Ängebyes_ES
AutorSimon, Nilses_ES
AutorSalcido, Jairaes_ES
AutorMartinez-Martinez, Arisaies_ES
AutorMunoz-Islas, Enriquetaes_ES
AutorJimenez-Andrade, Juan Migueles_ES
AutorSvensson, Camilla I.es_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número12es_ES
Rango de páginas2814-2828es_ES
URL relacionadahttps://doi.org/10.1097/j.pain.0000000000003343
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen165es_ES

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