Abstract
To examine regulatory effects of β-catenin on the biosynthesis and release of substance P, a rat chronic constriction injury (CCI) model and a rat dorsal root ganglion (DRG) cell culture model were used in the present study. The CCI treatment significantly induced the overall expression of β-catenin (158 ± 6% of sham) in the ipsilateral L5 DRGs in comparison with the sham group (109 ± 4% of sham). The CCI-induced aberrant expression of β-catenin was significantly attenuated by oral administration of diclofenac (119 ± 6% of the sham value; 10 mg/kg). Importantly, aberrant nuclear accumulation of β-catenin in cultured DRG cells resulted in up-regulation of the PPT-A mRNA expression and the substance P release. The up-regulation of both the PPT-A mRNA expression and the substance P release by either a GSK-3β inhibitor TWS119 (10 μM) or a Wnt signaling agonist Wnt-3a (100 ng/ml) were significantly abolished by an inhibitor of cyclooxygenase-2 (COX-2; NS-398, 1 μM). Collectively, these data suggest that nociceptive input-activated β-catenin signaling plays an important role in regulating the biosynthesis and release of substance P, which may contribute to the inflammation responses related to chronic pain.
Highlights
Substance P, encoded by the preprotachykinin-A (PPT-A) gene, is synthesized in the dorsal root ganglion (DRG) neurons
We sought to investigate β-catenin expression and its nuclear accumulation in L5 DRG cells of constriction injury (CCI) rats using the remaining sections of the same paraffin-embedded L5 DRG specimens from CCI rats in our previous study [16]
The CCI-induced total expression of β-catenin in ipsilateral L5 DRGs was significantly inhibited by diclofenac (109 ± 3% of sham, n = 4) in ipsilateral L5 DRGs (Fig 1B)
Summary
Substance P, encoded by the preprotachykinin-A (PPT-A) gene, is synthesized in the dorsal root ganglion (DRG) neurons. The nociceptive stimuli-evoked release of substance P from cultured DRG cells could be significantly attenuated by the inhibition of COX-2 [1,2,3]. Intrathecal injection of substance P induced spinal prostaglandin E2 release and thermal hyperalgesia can be reversed by spinal COX-2 inhibition [4,5]. The deletion of the PPT-A gene could reduce the stimulus-induced surface insertion of delta-opioid receptors and abolish delta-opioid receptor-mediated spinal analgesia and morphine tolerance [6]. PLOS ONE | DOI:10.1371/journal.pone.0129701 June 8, 2015
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