Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo

Abstract

The role of the cytokine leukemia inhibitory factor (LIF) in axotomy‐induced sprouting of postganglionic sympathetic fibres into the dorsal root ganglia was examined in the adult rat. Immunocytochemistry was used to study the distribution and density of tyrosine hydroxylase‐immunoreactive (TH‐IR) fibres within the lumbar dorsal root ganglia and lumbar spinal nerves 14 days following continuous intrathecal infusion of LIF (0.33 mg ml−1), or 14 days following unilateral peripheral nerve axotomy. In LIF‐treated animals, numerous pericellular TH‐IR basket‐like structures were observed surrounding sensory neurones, which were absent from controls. The number of TH‐IR fibres within the L3, L4 and L5 spinal nerves was significantly higher in LIF‐treated animals than in control or saline‐treated animals (P < 0.01, Student's t test). Unilateral ligation of the L4 spinal nerve or unilateral sciatic nerve ligation was also associated with the formation of TH‐IR baskets around sensory neurones and a significant increase in the number of TH‐IR fibres within the lumbar spinal nerves (P < 0.01, Student's t test). The percentage of neurones surrounded by TH‐IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy was significantly reduced in animals treated continuously for 2 weeks with a monoclonal antibody against the LIF receptor motif, gp130 (0.833 mg ml−1) (P < 0.05, Mann‐Whitney U test). Antibody treatment did not reduce the axotomy‐induced increase in TH‐IR fibres within lumbar spinal nerves. These results demonstrate that exogenous application of the axotomy‐associated cytokine LIF is associated with sprouting of uninjured postganglionic sympathetic neurones around sensory neurones within the dorsal root ganglion. It is likely that increased LIF expression following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following peripheral nerve injury.

Expression of α2‐adrenergic receptors in rat primary afferent neurones after peripheral nerve injury or inflammation

“…It is possible that whatever factors (e.g. leukemia inhibitory factor, Thompson & Majithia, 1998) and processes stimulate DRG neurones with transected fibres to respond with growth may spread to adjacent uninjured neurones and cause them to undergo similar alterations.…”

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

“…DRG cells receive signals that peripheral nerve injury has occurred via retrograde axonal transport from the trauma site. These retrogradely transported signals trigger sympathetic nerve sprouting into DRG (205,308). As a result of nerve damage-induced retrogradely transported signals, glial cells within the DRG (called satellite cells) proliferate (248) and become activated (343); macrophages are recruited to the DRG as well (63,176).…”

“…First, immune-derived substances such as leukemia inhibitory factor (LIF) (306), IL-6 (127), and NGF (163,172,261) are released at the injury site and are retrogradely transported by both intact as well as injured axons (72,204,248,308). These retrogradely transported signals in intact L 4 nerves result in increased DRG neuronal expression of BDNF mRNA and protein, vanilloid receptors type 1 (VR1) mRNA and protein, calcitonin gene-related peptide (CGRP) mRNA, preprotachykinin (PPT) mRNA and its protein product substance P, and galanin (72,73,118,177,308,309), as well as increased expression of PN3, a tetrodotoxin-resistant sodium channel subunit (238). This pattern contrasts what is observed after transection of all nerves in a bundle (axotomy), namely, downregulation of DRG expression of VR1 (191), substance P (272), CGRP (272), and PN3 (22).…”

Estudo experimental comparativo da ação das neurocinas cardiotrofina-1 e oncostatina-m na regeneração nervosa periférica

“…Também fazem parte deste grupo, CNTF, LIF, GPA e as interleucinas 6 e 11 (IL-6/IL11) (HOPKINS; ROTHWELL, 1995). Nos chamou a atenção que em estudos prévios (ADLER et al, 1979;GEARING et al, 1987;YAMAMORI et al, 1989;RICHARDSON, 1994;PEREIRA, 1998;MAJITHIA, 1998) o CNTF e o LIF estimularam a regeneração nervosa após a sua administração sobre a lesão de nervos ciáticos de camundongos adultos.…”

“…Previous studies (ADLER et al, 1979;GEARING et al, 1987;YAMAMORI et al, 1989;RICHARDSON, 1994;PEREIRA, 1998;MAJITHIA, 1998) demonstrated that CNTF and LIF stimulated nerve regeneration after their administration on lesion of adult mice sciatic nerves.…”