Disruption of Spinal Noradrenergic Activation Delays Recovery of Acute Incision-Induced Hypersensitivity and Increases Spinal Glial Activation in the Rat

Overview

Journal J Pain

Specialties Neurology
Psychiatry

Date 2015 Nov 8

PMID 26545342

Citations 9

Authors

Vipin Arora

Carlos Eduardo Morado-Urbina

Carol A Aschenbrenner

Ken-Ichiro Hayashida

Fuzhou Wang

Thomas J Martin

James C Eisenach

Christopher M Peters

Affiliations

Soon will be listed here.

Abstract

Unlabelled: Results of clinical studies suggest that descending inhibitory controls from the brainstem are important for speeding recovery from pain after surgery. We examined the effects of destroying spinally projecting noradrenergic neurons via intrathecally administered antibody to dopamine β-hydroxylase conjugated to saporin (DβH-saporin) on recovery in an acute incisional pain model. Mechanical and thermal paw withdrawal thresholds and nonevoked spontaneous guarding scores were tested for several weeks postoperatively and analyzed using mixed effects growth curve modeling. DβH-saporin treatment resulted in a significant prolongation in the duration of mechanical and to a lesser degree thermal hypersensitivity in the ipsilateral paw of incised rats but did not increase the duration of spontaneous guarding. DβH-saporin treatment was also associated with increased microglial and astrocyte activation in the ipsilateral spinal cord 21 days after incision compared with immunoglobulin G-saporin treated controls. Chronic intrathecal administration of the α2 adrenergic receptor antagonist atipamezole (50-200 μg/d) produced similar effects. These data suggest that spinally projecting noradrenergic pathways and spinal α2 adrenergic receptor activation are important for speeding recovery from hypersensitivity after surgical incision possibly by reducing spinal glial activation. Interventions that augment the noradrenergic system might be important to speed recovery from pain after surgery.

Perspective: Endogenous descending spinal noradrenergic activation promotes resolution of incision-induced hypersensitivity and inhibits spinal microglial and astrocyte activation in part through α2 adrenergic receptors.

Citing Articles

Mechanisms and treatments of chronic pain after traumatic brain injury.

Chen Q, Bharadwaj V, Irvine K, Clark J Neurochem Int. 2023; 171:105630.

PMID: 37865340 PMC: 11790307. DOI: 10.1016/j.neuint.2023.105630.

Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition.

Suto T, Kato D, Koibuchi I, Arai Y, Ohta J, Hiroki T Sci Rep. 2023; 13(1):5526.

PMID: 37016045 PMC: 10073110. DOI: 10.1038/s41598-023-32512-9.

Activation of locus coeruleus-spinal cord noradrenergic neurons alleviates neuropathic pain in mice via reducing neuroinflammation from astrocytes and microglia in spinal dorsal horn.

Li J, Wei Y, Zhou J, Zou H, Ma L, Liu C J Neuroinflammation. 2022; 19(1):123.

PMID: 35624514 PMC: 9145151. DOI: 10.1186/s12974-022-02489-9.

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.

Arora V, Morado-Urbina C, Gwak Y, Parker R, Kittel C, Munoz-Islas E Mol Pain. 2021; 17:1744806921997206.

PMID: 33829907 PMC: 8040570. DOI: 10.1177/1744806921997206.

Loss of diffuse noxious inhibitory control after traumatic brain injury in rats: A chronic issue.

Irvine K, Sahbaie P, Ferguson A, Clark J Exp Neurol. 2020; 333:113428.

PMID: 32745472 PMC: 11793995. DOI: 10.1016/j.expneurol.2020.113428.

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