Table 1.

Impairment of descending noradrenergic system in neuropathic pain: evidence from animal models.

Animal model	Preclinical phenotype	Reference
Spinal nerve ligation	Enhanced stimulus-evoked and spontaneous firing reduced by clonidine	Patel et al., 2018
L5-L6 spinal nerve ligation	Increased extracellular glutamate in the LC and impaired pain-evoked endogenous analgesia after nerve injury	Kimura et al., 2015
L5-L6 spinal nerve ligation	Mechanical hypersensitivity reduced by α2-agonists	Hayashida et al., 2008
Streptozotocin-induced diabetic rats	Mechanical allodynia and thermal hyperalgesia reduced by duloxetine	Kinoshita et al., 2013
Rats with tibial nerve transection	Mechanical and cold allodynia and heat hypersensitivity, all increased by α2-antagonists	Hughes et al., 2013
Incisional pain model combined with DβH-saporin	Selective degeneration of NA neurons with delayed recovery of mechanical hypersensitivity and increased spinal glial activation reduced by α2-agonists	Arora et al., 2016

LC, locus coeruleus; DβH-saporin, dopamine β-hydroxylase conjugated to saporin; NA, noradrenaline.