Spatio-temporal pattern of induction of bradykinin receptors and inflammation in rat dorsal root ganglia after unilateral nerve ligation

Abstract

Expression of bradykinin receptors was analyzed in freshly isolated dorsal root ganglion neurons of the ipsi- and contralateral segments L4/L5, L2/L3, and T12/T13 two to twenty days after unilateral injury of the adult rat sciatic nerve using gold labeled bradykinin. The number of infiltrating leucocytes was investigated by flow cytometry. Sciatic nerve injury transiently increased the proportion of neurons expressing bradykinin receptors not only in the ipsilateral ganglia L4/L5, but also in the homonymous contralateral ganglia and also bilaterally in the adjacent ganglia L2/L3. Neurons of the ganglia T12/T13 were not affected. The time course of upregulation was different between neurons of the injured nerve and uninjured ones. Furthermore, the proportion of neurons expressing a high density of receptors increased also bilaterally in ganglia L4/L5 and L2/L3. As on the ipsilateral side, the increase in neurons expressing bradykinin receptors in the contralateral homonymous ganglia was due to an induction of the B1 receptor subtype and an upregulation of the B2 subtype. As a possible source for stimulating factors for induction of bradykinin receptors the number of macrophages and lymphocytes was investigated two to twenty days after nerve ligation. No increase was observed prior to day ten and only in ipsilateral ganglia L4/L5, not contralaterally and not in adjacent ganglia L2/L3 and T12/T13. The experiments show that the induction of bradykinin receptors following a unilateral nerve lesion is not restricted to neurons projecting into the damaged nerve but is (i) bilateral, (ii) different in time course between injured and uninjured neurons, and (iii) locally confined to neurons of the adjacent ganglia. Macrophages and lymphocytes are increased after ten day ligation only in the affected ganglia and are probably not involved in the induction of bradykinin receptors.

Aβ42-induced Increase in Neprilysin Is Associated with Prevention of Amyloid Plaque Formation in Vivo

“…Most interestingly, an increase in the expression of NEP-related genes such as tachykinins and bradykinin receptors in response to unilateral neuronal injury is also found contralaterally to the lesion site (40,41). Therefore, increased NEP expression throughout the brain in our study may very well be initiated by the damage done to the tissue by our injections during the deposition of the fibrillar A␤ 42 and sustained because of the stability of the injected A␤ 42 fibrils in brain tissue.…”

Reduced Nerve Injury-Induced Neuropathic Pain in Kinin B1Receptor Knock-Out Mice

“…Increased levels of B 1 and B 2 receptor mRNA or protein have been found in dorsal root ganglia (DRGs) after sciatic nerve constriction in rats and mice (Petersen et al, 1998;Eckert et al, 1999;Levy and Zochodne, 2000;Yamaguchi-Sase et al, 2003;Rashid et al, 2004). Of note, the systemic administration of B 1 or B 2 receptor antagonists has been found to reduce thermal hyperalgesia and mechanical allodynia produced by sciatic nerve constriction in rats (Levy and Zochodne, 2000;Yamaguchi-Sase et al, 2003;Gougat et al, 2004).…”

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…Two and 10 -14 days after unilateral sciatic nerve ligation in the rat, an increase in the number of both bradykinin receptor subtypes was observed in ipsilateral L4/L5 DRG neurons (168,573,574). This increase included a de novo expression of B 1 receptors and an enhancement of the density of preexisting B 2 receptors, and it was accompanied by an increase in the number of bradykinin binding sites on individual neurons.…”