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dc.contributor.authorArora, Vipin
dc.contributor.authorMorado-Urbina, Carlos Eduardo
dc.contributor.authorGwak, Young S
dc.contributor.authorParker, Renee A
dc.contributor.authorKittel, Carol A
dc.contributor.authorMunoz-Islas, Enriqueta
dc.contributor.authorMiguel Jimenez-Andrade, Juan
dc.contributor.authorRomero-Sandoval, E Alfonso
dc.contributor.authorEisenach, James C
dc.contributor.authorPeters, Christopher M
dc.date.accessioned2021-04-14T12:33:45Z
dc.date.available2021-04-14T12:33:45Z
dc.date.issued2021-04-08
dc.identifier.urihttp://hdl.handle.net/10713/15403
dc.description.abstractBeta 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.en_US
dc.description.urihttps://doi.org/10.1177/1744806921997206en_US
dc.language.isoenen_US
dc.publisherSAGE Publications Inc.en_US
dc.relation.ispartofMolecular painen_US
dc.subjectPostoperative painen_US
dc.subjectacute to chronic pain transitionen_US
dc.subjectglial plasticityen_US
dc.subjectgrowth curve modelingen_US
dc.subjectsurgeryen_US
dc.titleSystemic 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 hypersensitivityen_US
dc.typeArticleen_US
dc.identifier.doi10.1177/1744806921997206
dc.identifier.pmid33829907
dc.source.volume17
dc.source.beginpage1744806921997206
dc.source.endpage
dc.source.countryUnited States


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