Human PTEN adenoviral particles

The phosphatase and tensin homolog deleted from chromosome 10 (PTEN) pathway has been extensively examined in many cancer studies. Only a few reports have suggested that PTEN may affect pain; however, evidence for the role of PTEN in pain regulation is still lacking. Here, researchers found that chronic constriction injury (CCI) surgery in rats induced downregulation of spinal PTEN and upregulation of phosphorylated PTEN (phospho-PTEN) and phosphorylated mammalian target of rapamycin (phospho-mTOR). After examining such changes in endogenous PTEN in neuropathic rats, researchers explored the effects of modulating the spinal PTEN pathway on nociceptive behavior. Normal rats exhibited mechanical allodynia after intrathecal (i.t.) injection of adenovirus-mediated PTEN antisense oligonucleotides (Ad-antisense PTEN). Furthermore, upregulation of spinal PTEN by intrathecal adenovirus-mediated PTEN (Ad-PTEN) significantly prevented the development of CCI-induced nociceptive sensitization, thermal hyperalgesia, mechanical allodynia, cold allodynia, and weight-bearing deficits in neuropathic rats. Furthermore, upregulation of spinal PTEN by intrathecal Ad-PTEN significantly attenuated CCI-induced microglial and astrocyte activation, upregulation of tumor necrosis factor-α (TNF-α) and phosphorylated mTOR, and downregulation of PTEN 14 days after injury in neuropathic rats. These findings suggest that PTEN plays a critical beneficial role in rodent models of neuropathic pain.

Here, to verify that Ad-PTEN is able to upregulate the production of PTEN in the spinal cord, the researchers prepared the following three groups of rats: (1) naïve rats plus i.t. vector, (2) naive rats plus i.t. Ad-GFP, and (3) naïve rats plus i.t. Ad-PTEN. The researchers observed no significant difference in spinal PTEN expression between naive rats plus i.t. vector (Figure 1A) and rats examined 14 days after i.t. injection of Ad-GFP (Figure 1B), while PTEN immunoreactivity increased after 14 days of i.t. Ad-PTEN (Figure 1C). Quantification of immunoreactivity results (Figure 1D) further confirmed the upregulation of PTEN in the naive rats plus i.t. Ad-PTEN group 14 days after i.t. injection. Confocal double immunostaining images of the lumbar dorsal gray matter further confirmed that in the naïve rats administered i.t. Ad-PTEN, most PTEN signals colocalized with GFAP-positive cells (astrocytes; Figure 1F ) more often than with NeuN-positive cells (neuronal cells; Figure 1E ) or OX-42-positive cells (microglia; Figure 1G ).

Figure 1. The effects of i.t. injection of Ad-PTEN on PTEN in the dorsal lumbar spinal cord. (Huang S Y, et al., 2015)