Lidocaine Inhibits HCN Currents in Rat Spinal Substantia Gelatinosa Neurons.
Anesth Analg
; 122(4): 1048-59, 2016 Apr.
Article
in En
| MEDLINE
| ID: mdl-26756913
ABSTRACT
BACKGROUND:
Lidocaine, which blocks voltage-gated sodium channels, is widely used in surgical anesthesia and pain management. Recently, it has been proposed that the hyperpolarization-activated cyclic nucleotide (HCN) channel is one of the other novel targets of lidocaine. Substantia gelatinosa in the spinal dorsal horn, which plays key roles in modulating nociceptive information from primary afferents, comprises heterogeneous interneurons that can be electrophysiologically categorized by firing pattern. Our previous study demonstrated that a substantial proportion of substantia gelatinosa neurons reveal the presence of HCN current (Ih); however, the roles of lidocaine and HCN channel expression in different types of substantia gelatinosa neurons remain unclear.METHODS:
By using the whole-cell patch-clamp technique, we investigated the effect of lidocaine on Ih in rat substantia gelatinosa neurons of acute dissociated spinal cord slices.RESULTS:
We found that lidocaine rapidly decreased the peak Ih amplitude with an IC50 of 80 µM. The inhibition rate on Ih was not significantly different with a second application of lidocaine in the same neuron. Tetrodotoxin, a sodium channel blocker, did not affect lidocaine's effect on Ih. In addition, lidocaine shifted the half-activation potential of Ih from -109.7 to -114.9 mV and slowed activation. Moreover, the reversal potential of Ih was shifted by -7.5 mV by lidocaine. In the current clamp, lidocaine decreased the resting membrane potential, increased membrane resistance, delayed rebound depolarization latency, and reduced the rebound spike frequency. We further found that approximately 58% of substantia gelatinosa neurons examined expressed Ih, in which most of them were tonically firing.CONCLUSIONS:
Our studies demonstrate that lidocaine strongly inhibits Ih in a reversible and concentration-dependent manner in substantia gelatinosa neurons, independent of tetrodotoxin-sensitive sodium channels. Thus, our study provides new insight into the mechanism underlying the central analgesic effect of the systemic administration of lidocaine.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Substantia Gelatinosa
/
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
/
Anesthetics, Local
/
Lidocaine
/
Neurons
Limits:
Animals
Language:
En
Journal:
Anesth Analg
Year:
2016
Document type:
Article