The Characterization of AT1 Expression in the Dorsal Root Ganglia After Chronic Constriction Injury

Abstract

To clarify the role of Angiotensin II in the regulation of sensory signaling, we characterized the AT expression in neuronal subpopulation of lower lumbar dorsal root ganglia under normal conditions and its alteration in neuropathic pain model. The characterization of AT expression was done under control and after the chronic constriction injury induced by four loose ligatures of the sciatic nerve representing the model of posttraumatic painful peripheral neuropathy. Major Angiotensin II receptor type was expressed in approximately 43 % of small-sized and 62 % of large-sized neurons in control. The AT overexpression after sciatic nerve ligation lasting 7 days was detected predominantly in small-sized AT immunoreactive neurons (about 38 % increase). Chronic constriction injury caused a statistically marked increase in number of the small-sized peptidergic (CGRP immunoreactive) neuronal subpopulation expressing AT (about 64 %). The subpopulations of AT-immunoreactive and nonpeptide-containing primary sensory neurons revealed by IB4 binding, tyrosine hydroxylase- and parvalbumin-immunoreactive neurons were not markedly changed. Our results indicate that: (1) the AT overexpression after the chronic constriction injury is an important factor in Angiotensin II-potentiated pain perception; (2) Angiotensin II is involved in pathological mechanisms of neuropathic pain and this effect can be mediated perhaps in combination with other neuropeptides synthesized in the primary sensory neurons.

Shedding Light on the Pharmacological Interactions between μ-Opioid Analgesics and Angiotensin Receptor Modulators: A New Option for Treating Chronic Pain

“…AT2 mRNA was found in the DRG and sciatic nerve of rats [43,127]. The receptor protein was found by many research groups on neurons (IB4+ [132]), satellite cells [106,127], and CD3+ T-cells [106] and in the rat DRG as well [101,106,107,110,125,130]. Indeed, in a few studies, the AT2 antibody specificity was verified on AT2R KO mice, further reinforcing the results [37,123].…”

“…Moreover, it can be found in different brain regions, such as the spinal trigeminal tract and raphe nuclei [122]. These data also provide strong evidence on a large amount of AT1aR, and smaller amounts of AT1bR mRNA [43,127,129,132], and the receptor protein [31,36,39,40,123,125,[127][128][129] was also shown in the mentioned regions. In the DRG, the receptor protein was found on satellite cells and neurons of all sizes with a greater extent on smaller ones [36,110,128,130].…”

“…With respect to the receptors, several studies have reported on the distribution of AT1R on key points related to nociceptive transmission both in mice [39,40] and rats [31,36,43,[122][123][124][125][126][127][128][129]. These areas include sciatic nerve [31,127,130], DRG [36,43,123,125,[127][128][129][130][131], and spinal cord [22,39,40,129,132]. Moreover, it can be found in different brain regions, such as the spinal trigeminal tract and raphe nuclei [122].…”

The differences in the anatomy of the thoracolumbar and sacral autonomic outflow are quantitative

“…Catecholaminergic cell bodies have a more widespread distribution than generally acknowledged [ 2 , 4 , 6 ]. They are found in the trigeminal [ 23 , 24 ], geniculate [ 25 ], inferior glossopharyngeal [ 26 – 37 ], superior [ 31 , 38 ], and inferior [ 26 , 28 , 29 , 31 , 32 , 34 , 35 , 37 – 47 ] vagal ganglia, and in dorsal root ganglia at all spinal levels [ 28 , 31 , 48 – 59 ]. Moreover, the generally accepted parasympathetic ganglia of the head [ 2 ], which include the ciliary [ 60 – 69 ], the otic [ 69 ], the pterygopalatine [ 69 – 72 ] and the submandibular ganglia [ 69 , 73 – 78 ], all contain catecholaminergic cell bodies.…”

“…Many of these proximal cell bodies subsequently nest in the sympathetic trunk. Other proximal locations, however, include the spinal nerve roots [ 84 – 99 ], dorsal root ganglia [ 28 , 31 , 48 – 59 , 95 ], and white and gray rami communicantes [ 85 – 91 , 95 – 98 , 106 – 111 ]. In the pelvic area, usually characterized as parasympathetic, these proximal locations of ganglionic cells also exist, both in sacral nerve roots [ 84 , 93 , 99 ] and in the proximal part of the pelvic splanchnic nerves [ 16 , 17 , 93 , 112 – 114 ].…”