Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Abstract

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line-derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.

The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain

“…Several previous studies have established that pERK expression levels are elevated in the lumbar spinal cord of rats receiving a unilateral ITI of Walker 256 cells, in the pain state (Wang L.-n. et al, 2011 ; Chen et al, 2012 ; Hu et al, 2015 ; Zhu et al, 2015 ; Ding et al, 2017 ; Sun et al, 2017 ). In BCIBP-rats administered a bolus dose of J-2156 at 10 mg/kg i.p., pERK expression levels in the lumbar spinal dorsal horns at the time of peak effect of anti-hypersensitivity were significantly ( p ≤ 0.05) decreased c.f .…”

Normalizing JMJD6 Expression in Rat Spinal Dorsal Horn Alleviates Hyperalgesia Following Chronic Constriction Injury

“…Different possibilities can be taken into consideration. JMJD6 exerts its inhibitory function through the demethylation of H4R3me2a, and the level of histone methylation influences the synaptic plasticity in the nervous system (Epstein et al, 2001 ; Ikeda et al, 2012 ; Na et al, 2015 ; Aprelikova et al, 2016 ; Ding et al, 2017 ). Furthermore, histone demethylation may support a reversal of the pathologic processes in NPP (Semenza, 2000 ).…”

“…Catheter implantation was performed in anesthetized rats (1–3% isoflurane). The lumbar intrathecal catheter was implanted into the subarachnoid space as previously described (Ding et al, 2017 ). The success of catheter insertion was judged using the intrathecal lidocaine test.…”

Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury

“…For rats that were assigned to receive C646 (an antagonist of p300 acetyltransferase) and Axitinib (an inhibitor of VEGF signaling), an intrathecal catheter was placed before the crush injury. The intrathecal catheter was placed according to our previous study (Ding et al, 2017b ). Briefly, the bony arch of the vertebra was exposed between the L4 and L5 vertebrae.…”