Dexmedetomidine relieves neuropathic pain by inhibiting hyperpolarization-activated cyclic nucleotide-gated currents in dorsal root ganglia neurons.

Abstract

This study was designed to examine the effect and mechanism of dexmedetomidine (Dex) on neuropathic pain (NP). The NP model was established by performing chronic sciatic nerve constriction injury (CCI). Seven days after CCI surgery, the rats were injected intraperitoneally with Dex, ZD7288 (an HCN channel inhibitor), and saline, respectively. The paw withdrawal threshold to mechanical stimulation and the thermal withdrawal latency tests were performed. After administration, the L4, L5 dorsal root ganglia (DRG) neurons of rats were isolated. In addition, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels subtype plasmids were transfected into human embryonic kidney (HEK)293 cells. Whole-cell clamp recordings were used to examine the properties of HCN currents (Ih) expressed in HEK293 cells and DRG neurons. After surgery, the paw withdrawal threshold to mechanical stimulation and thermal withdrawal latency were reduced, the HCN currents (Ih) amplitude of DRG neurons was increased, and the semiactivated voltage (V1/2) value was decreased in CCI rats (P<0.05). CCI rats treated with Dex or ZD7288 had reduced mechanical and thermal hyperalgesia. The Ih amplitude was lower and the V1/2 value was increased in DRG neurons in CCI rats treated with Dex or ZD7288 (P<0.05). In addition, Dex inhibited HCN1 and HCN2 currents in HEK293 cells; caused a decrease in maximal currents, an increase in the inhibition rate of Ih, and a negative shift in V1/2 (P<0.05). Taken together, our finding suggested that Dex alleviates NP and the effect is likely because of the inhibition of HCN currents.

• Authors: Yingcong Yang, Zhongyuan Xia, Qingtao Meng, Kang Liu, Yeda Xiao, Liwei Shi
• Journal: Neuroreport (Neuroreport) Vol. 29 Issue 12 Pg. 1001-1006 (08 15 2018) ISSN: 1473-558X [Electronic] England
• PMID: 29912028 (Publication Type: Journal Article)

Chemical References

• Analgesics, Non-Narcotic
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
• Dexmedetomidine

Topics

• Analgesics, Non-Narcotic (pharmacology, therapeutic use)
• Animals
• Cells, Cultured
• Dexmedetomidine (pharmacology, therapeutic use)
• Ganglia, Spinal (drug effects, physiopathology)
• HEK293 Cells
• Humans
• Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels (antagonists & inhibitors, physiology)
• Male
• Membrane Potentials (drug effects, physiology)
• Neuralgia (drug therapy, physiopathology)
• Neurons (drug effects, physiology)
• Patch-Clamp Techniques (methods)
• Rats
• Rats, Sprague-Dawley