CCI HCN2 mRNA Liu et al demonstrated

CCI lowers the
expression of HCN1 and HCN2 mRNA

et al demonstrated that neuropathy induced by CCI in left sciatic nerve
decreased the expression of HCN1 and HCN2 mRNA in peripheral nerve system and
spinal cord. The hind paw withdraw latency to thermal stimulation and hind paw
withdraw threshold to mechanical stimulation were decreased in injured rats. The
chronic constriction injury was induced by exposing the left sciatic nerve at
the middle of the thigh by blunt dissection through biceps femoris. 4 ligatures
(4.0 chromic gut) with 1 mm spacing were tied loosely around about 7 mm of exposed
nerve, adjacent  to the sciatic’s
trifurcation (Bennett et al.,1987). The paw withdraw latency and paw withdraw
threshold were decreased in chronic constriction injured rats at 7th,
10th and 14th day after injury (Liu et al., 2016). The
author reported that perfusion with 50 uM ZD7288 (specific Ih blocker) for 15
min significantly decreased the resting membrane potential and increased the
action potential rising time. It also caused a significant decrease in the
repetitive firing number and the V0.5 (the membrane potential at
which HCN channel was half-activated). This indicated that the activated HCN channels
help to stabilize the resting membrane potential in the resting state and drive
the membrane potential depolarization to the threshold of action potential,
causing in the elevation of neuronal excitability (Tu et al., 2004). CCI
induced nerve degeneration, which was observed by performing nissl staining
method on dorsal root ganglions. In CCI dorsal root ganglions, degenerated
nerve cells was found, which was indicated by the disappearance of nissl bodies
and lost of nucleoli 14 days after CCI (Liu et al., 2016).

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induced neuropathy, the injured sciatic nerve leads to increased spontaneous
firing or alterations in the conduction of neurotransmitter, resulting in
chronic or persistent pain. HCN is correlated to Ih (Hyperpolarization-activated
current) current, a cation current which is activated by membrane
hyperpolarization, results in the formation of resting membrane potential (Liu
et al., 2016). The activation of I h is very
sensitive to intracellular adenylate cyclase and cAMP activities. Increase in
cAMP (during ?-receptor activation) lead to depolarization, whereas decrease in
cAMP (during muscarinic receptor activation) lead to hyperpolarization (Ingram
et al., 1996). Cui et al reported that Prostaglandin E2 causes
the activation of adenylate cyclase to increase intracellular cyclic AMP, which
in turn activates protein kinase A. The activation of protein kinase A leads to
increased levels of protein phosphorylation, this results in the enhancement of
neuronal sensitivity to excitatory chemical agents (Cui et al., 1995).Thus the prostaglandins
enhance the excitability of sensory neurons and this sensitization may occur
due to the suppression of a sustained or delayed rectifier type of K+ channel,
that modulates the threshold of AP firing. Therefore the inhibition of these K+ channels
results in increased generation of Aps. Suppression of I K
through PGE2 causes the reduction
in the firing threshold of the neurons which further leads to increase in
membrane resistance (Baccaglini et al., 1983).In DRG neurons after the nerve
injury if the spontaneous action potential is negative due to hyperpolarization
and lasts long enough to activate Ih, then this Ih will contribute to facilitation
of the firing discharges. Therefore the discharge frequency of spontaneously
active DRG neurons may be reduced by Ih inhibition through a2-adrenoceptor
activation (Yagi et al., 1998).