Systemic administration of a β2-adrenergic receptor agonist reduces mechanical allodynia and suppresses the immune response to surgery in a rat model of persistent post-incisional hypersensitivity

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-09-15T00:30:27Z
Fecha de publicación2021-01-01
ResumenBeta 2 adrenergic receptor (β2 AR) activation in the central and peripheral nervous system has been implicated in nociceptive processing in acute and chronic pain settings with anti-inflammatory and anti-allodynic effects of β2-AR mimetics reported in several pain states. In the current study, we examined the therapeutic efficacy of the β2-AR agonist clenbuterol in a rat model of persistent postsurgical hypersensitivity induced by disruption of descending noradrenergic signaling in rats with plantar incision. We used growth curve modeling of ipsilateral mechanical paw withdrawal thresholds following incision to examine effects of treatment on postoperative trajectories. Depletion of spinal noradrenergic neurons delayed recovery of hypersensitivity following incision evident as a flattened slope compared to non-depleted rats (-1.8 g/day with 95% CI -2.4 to -1.085, p < 0.0001). Chronic administration of clenbuterol reduced mechanical hypersensitivity evident as a greater initial intercept in noradrenergic depleted (6.2 g with 95% CI 1.6 to 10.8, p = 0.013) and non-depleted rats (5.4 g with 95% CI 1.2 to 9.6, p = 0.018) with plantar incision compared to vehicle treated rats. Despite a persistent reduction in mechanical hypersensitivity, clenbuterol did not alter the slope of recovery when modeled over several days (p = 0.053) or five weeks in depleted rats (p = 0.64). Systemic clenbuterol suppressed the enhanced microglial activation in depleted rats and reduced the density of macrophage at the site of incision. Direct spinal infusion of clenbuterol failed to reduce mechanical hypersensitivity in depleted rats with incision suggesting that beneficial effects of β2-AR stimulation in this model are largely peripherally mediated. Lastly, we examined β2-AR distribution in the spinal cord and skin using in-situ hybridization and IHC. These data add to our understanding of the role of β2-ARs in the nervous system on hypersensitivity after surgical incision and extend previously observed anti-inflammatory actions of β2-AR agonists to models of surgical injury.es_ES
Doihttps://doi.org/10.1177/1744806921997206es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/2428
Idiomaeses_ES
EditorialSAGE Publicationses_ES
RelaciónMolecular Paines_ES
URL relacionadohttps://doi.org/10.1177/1744806921997206es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteMolecular Pain
TítuloSystemic administration of a β2-adrenergic receptor agonist reduces mechanical allodynia and suppresses the immune response to surgery in a rat model of persistent post-incisional hypersensitivityes_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorArora, Vipin
AutorMorado-Urbina, Carlos Eduardo
AutorGwak, Young S
AutorParker, Renee A
AutorKittel, Carol A
AutorMunoz-Islas, Enriqueta
AutorJimenez-Andrade, Juan Miguel
AutorRomero-Sandoval, E. Alfonso
AutorEisenach, James C
AutorPeters, Christopher M
AutorArora, Vipines_ES
AutorMorado-Urbina, Carlos Eduardoes_ES
AutorGwak, Young Ses_ES
AutorParker, Renee Aes_ES
AutorKittel, Carol Aes_ES
AutorMunoz-Islas, Enriquetaes_ES
AutorJimenez-Andrade, Juan Migueles_ES
AutorRomero-Sandoval, E. Alfonsoes_ES
AutorEisenach, James Ces_ES
AutorPeters, Christopher Mes_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
URL relacionadahttps://doi.org/10.1177/1744806921997206
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen17es_ES

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