OBJECTIVETo observe the expression and function of extraction.

METHODSReal-time reverse transcription PCR paralleled with vitro-established cRNA standard curves was applied to measure the expression of Nav1.8, Nav1.9 at 30 min, 2 h, 1 d, 3 d and 6 d respectively after extraction of rat right mandibular molars. The right mandibular molars were used as control.

RESULTSBoth Nav1.8 and Nav1.9 mRNA in right trigeminal ganglion showed little change after 30 min, and increased slowly after 2 h. Nav1.8, Nav1.9 mRNA expressions increased by 27% and 24.5% respectively compared to the left trigeminal ganglion after 3 d, reaching the highest level (P < 0.05), and then the expressions began decreasing from 6 d.

CONCLUSIONSThe pain caused by molar extraction is related to the up-regulation of expressions of sodium channels protein Nav1.8 and Nav1.9 mRNA, indicating the participation of sodium channels in regulations of peripheral tissue pain after molar extraction.

Animals ; Male ; NAV1.8 Voltage-Gated Sodium Channel ; NAV1.9 Voltage-Gated Sodium Channel ; Neuropeptides ; metabolism ; Pain, Postoperative ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar ; Sodium Channels ; metabolism ; Tooth Extraction ; Trigeminal Ganglion ; metabolism

OBJECTIVETo investigate changes of two sodium channels, PN(3) and NaN, during orofacial pain by occlusal trauma in rat.

METHODSExpressions of PN(3) mRNA and NaN mRNA in trigeminal ganglion were tested during various periods of persistent occlusal trauma with reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSIn groups, including control, occlusal trauma groups, PN(3) mRNA and NaN mRNA were all expressed in trigeminal ganglion neurons. In the control group, there were similar density values bilaterally. In the occlusal trauma group, the density values in gel electrophoresis of PN(3) mRNA and NaN mRNA on the intervention side were slightly greater than those on the control side.

CONCLUSIONSThe stimulation of occlusal trauma upregulates expressions of PN(3) mRNA and NaN mRNA, which suggests the signal occurring and conduction of chronic pain by occlusal trauma have the same molecular mechanism of sodium channel as inflammatory pain.

Animals ; Dental Occlusion, Traumatic ; physiopathology ; Facial Pain ; etiology ; Male ; NAV1.8 Voltage-Gated Sodium Channel ; RNA, Messenger ; biosynthesis ; Rats ; Rats, Sprague-Dawley ; Sodium Channels ; biosynthesis ; genetics ; Trigeminal Ganglion ; metabolism

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.
Analgesia ; Animals ; Ganglia, Spinal ; Growth Differentiation Factor 15 ; NAV1.8 Voltage-Gated Sodium Channel ; Rats ; Sensory Receptor Cells ; Sodium Channels ; Tetrodotoxin/pharmacology*

Animals ; Cells, Cultured ; NAV1.8 Voltage-Gated Sodium Channel ; metabolism ; Pain ; chemically induced ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Scorpion Venoms ; pharmacology ; Up-Regulation

Voltage-gated sodium channels (VGSCs) in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. However, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small-sized (<25 μm) acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow inactivation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nav1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 remarkably, suggesting BmK I as a valuable probe for studying Nav1.8. And Nav1.8 is an important target related to BmK I-evoked pain.
Aniline Compounds ; pharmacology ; Animals ; Cell Size ; Cells, Cultured ; Electrophysiological Phenomena ; drug effects ; Furans ; pharmacology ; Ganglia, Spinal ; cytology ; Kinetics ; Male ; NAV1.8 Voltage-Gated Sodium Channel ; metabolism ; Rats ; Rats, Sprague-Dawley ; Scorpion Venoms ; antagonists & inhibitors ; pharmacology ; Scorpions ; Sensory Receptor Cells ; drug effects ; metabolism ; physiology ; Sodium Channel Blockers ; pharmacology ; Voltage-Gated Sodium Channel Agonists ; pharmacology

OBJECTIVETo investigate the relationship between dental pain and Nav1.8 expression level by detecting the expression of voltage-gated sodium channel Nav1.8 in normal human dental pulps and painful pulp tissues.

METHODSImmunohistochemistry, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression of Nav1.8 in normal human dental pulp and painful dental pulp.

RESULTSNav1.8 expressed in dental pulps and the expression level of Nav1.8 increased significantly in painful dental pulps in comparison with normal dental tissues. The immunohistochemistry results revealed that Nav1.8 expression level in painful dental issue was 0.547 ± 0.049 in relative intensity,and in normal dental issue 0.356 ± 0.058 (P < 0.05). Western blotting showed similar results of 0.234 ± 0.030 vs 0.108 ± 0.012. RT-PCR results indicated that Nav1.8 mRNA expression level in painful dental issue was 7.130 ± 2.471 and in normal dental issue was 1.024 ± 0.295 (P < 0.05).

CONCLUSIONSThe expression level of Nav1.8 increased significantly in painful dental pulp tissue, suggesting that Nav1.8 may play an important role in the development and transmission of dental pain.

Adult ; Blotting, Western ; Dental Pulp ; metabolism ; pathology ; Gene Expression Regulation ; Humans ; Immunohistochemistry ; Middle Aged ; NAV1.8 Voltage-Gated Sodium Channel ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Toothache ; metabolism ; pathology ; Young Adult