title: Inflammation in dorsal root ganglia after peripheral nerve injury: effects of the sympathetic innervation.
abstract: Following a peripheral nerve injury, a sterile inflammation develops in sympathetic and dorsal root ganglia (DRGs) with axons that project in the damaged nerve trunk. Macrophages and T-lymphocytes invade these ganglia where they are believed to release cytokines that lead to hyperexcitability and ectopic discharge, possibly contributing to neuropathic pain. Here, we examined the role of the sympathetic innervation in the inflammation of L5 DRGs of Wistar rats following transection of the sciatic nerve, comparing the effects of specific surgical interventions 10-14 days prior to the nerve lesion with those of chronic administration of adrenoceptor antagonists. Immunohistochemistry was used to define the invading immune cell populations 7 days after sciatic transection. Removal of sympathetic activity in the hind limb by transecting the preganglionic input to the relevant lumbar sympathetic ganglia (ipsi- or bilateral decentralization) or by ipsilateral removal of these ganglia with degeneration of postganglionic axons (denervation), caused less DRG inflammation than occurred after a sham sympathectomy. By contrast, denervation of the lymph node draining the lesion site potentiated T-cell influx. Systemic treatment with antagonists of α1-adrenoceptors (prazosin) or β-adrenoceptors (propranolol) led to opposite but unexpected effects on infiltration of DRGs after sciatic transection. Prazosin potentiated the influx of macrophages and CD4(+) T-lymphocytes whereas propranolol tended to reduce immune cell invasion. These data are hard to reconcile with many in vitro studies in which catecholamines acting mainly via β2-adrenoceptors have inhibited the activation and proliferation of immune cells following an inflammatory challenge.
authors.affiliation: Neuroscience Research Australia, Randwick, NSW 2031, and the University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: e.mclachlan@unsw.edu.au.
authors.forename: Elspeth M
authors.initials: EM
authors.lastname: McLachlan
authors.affiliation: Neuroscience Research Australia, Randwick, NSW 2031, and the University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
mesh_terms: D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000276:immunology / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D059348:Peripheral Nerve Injuries / Q000150:complications*; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000503:physiopathology*
keywords: Afferent neurones; CD4(+) T-cells; Chronic adrenoceptor blockade; Decentralization; Denervated lymph node; Macrophages; Neuroinflammation; Sciatic transection; Sympathectomy