Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain

In attempt to understand the underlying mechanisms of cancer-induced bone pain, we investigated the presence of two tetrodotoxin-resistant sodium channels, Nav1.8 (SNS/PN3) and Nav1.9 (SNS2/NaN), in dorsal root ganglia (DRG) neurons in an animal model of bone cancer pain. Thirty-six female Sprague-Dawley rats were randomized into three groups: Sham operation group (Sham), cancer-bearing animals killed after 7 days (C7) and cancer-bearing animals killed after 14 days group (C14). After establishment of bone cancer pain model, behavioral tests were carried out to determine the paw withdrawal threshold (PWT) of mechanical and thermal hyperalgesia, respectively. Real-time RT-PCR, Western bolt and Immunofluorescence were used to determine the mRNA and protein expression of Nav1.8 and Nav1.9 in ipsilateral lumbar 4-5 DRG. Compared to Sham group, PWT of mechanical and thermal hyperalgesia in C14 group displayed a significant decrease (P < 0.01) from post-operation day (POD) 5 and POD7 to the end point of the observation, respectively. Compared to Sham group, the relative mRNA expression of Nav1.8 and Nav1.9 exhibited a significant up-regulation in C14 group (8.9 times and 9 times, respectively, P < 0.01) but not C7 group (1.5 times and 2.4 times, respectively). Western blot and Immunofluorescence revealed an apparent increase of Nav1.8 (P < 0.05) and Nav1.9 (P < 0.05) protein in C14 group compared with Sham group. The up-regulation of mRNA and protein levels of Nav1.8 and Nav1.9 suggested their potential involvement in the development and maintenance of bone cancer pain.

► A rat model of bone cancer pain was established as previously described with minor revision.
► We examined pain-related behavioral changes and expression of Nav1.8 and Nav1.9.
► Expression of Nav1.8 and Nav1.9 was up-regulated in lumbar 4-5 DRG.
► The potential involvement of Nav1.8 and Nav1.9 in bone cancer pain was indicated.