CCI and hind paw withdraw threshold to mechanical

CCI (chronic constriction injury) reduces the HCN1 and HCN2 mRNA expressionLiuet al demonstrated that neuropathy induced by CCI (chronic constriction injury)in left sciatic nerve decreased the expression of HCN1 and HCN2 mRNA inperipheral nerve system and spinal cord. The hind paw withdraw latency tothermal stimulation and hind paw withdraw threshold to mechanical stimulationwere decreased in injured rats.

The chronic constriction injury was induced byexposing the left sciatic nerve at the middle of the thigh by blunt dissection throughbiceps femoris. 4 ligatures (4.0 chromic gut) with 1 mm spacing were tiedloosely around about 7 mm of exposed nerve, adjacent  to the sciatic’s trifurcation (Bennett etal.

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,1987). The paw withdraw latency and paw withdraw threshold were decreasedin chronic constriction injured rats at 7th, 10th and 14thday after injury (Liu et al., 2016). The author reported that perfusion with 50uM ZD7288 (specific Ih blocker) for 15 min significantly decreased the restingmembrane potential and increased the action potential rising time. It alsocaused a significant decrease in the repetitive firing number and the V0.

5(the membrane potential at which HCN channel was half-activated). Thisindicated that the activated HCN channels help to stabilize the restingmembrane potential in the resting state and drive the membrane potentialdepolarization to the threshold of action potential, causing in the elevationof neuronal excitability (Tu et al., 2004).

CCI induced nerve degeneration,which was observed by performing nissl staining method on dorsal rootganglions. In CCI dorsal root ganglions, degenerated nerve cells was found,which was indicated by the disappearance of nissl bodies and lost of nucleoli14 days after CCI (Liu et al., 2016).

  Mechanism: In CCIinduced neuropathy, the injured sciatic nerve leads to increased spontaneousfiring or alterations in the conduction of neurotransmitter, resulting inchronic or persistent pain. HCN is correlated to Ih (Hyperpolarization-activatedcurrent) current, a cation current which is activated by membranehyperpolarization, results in the formation of resting membrane potential (Liuet al., 2016). The activation of I h is verysensitive to intracellular adenylate cyclase and cAMP activities. Increase incAMP (during ?-receptor activation) lead to depolarization, whereas decrease incAMP (during muscarinic receptor activation) lead to hyperpolarization (Ingramet al.

, 1996). Cui et al reported that Prostaglandin E2 causesthe activation of adenylate cyclase to increase intracellular cyclic AMP, whichin turn activates protein kinase A. The activation of protein kinase A leads toincreased levels of protein phosphorylation, this results in the enhancement ofneuronal sensitivity to excitatory chemical agents (Cui et al., 1995).Thus the prostaglandinsenhance the excitability of sensory neurons and this sensitization may occurdue 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+ channelsresults in increased generation of Aps. Suppression of I Kthrough PGE2 causes the reductionin the firing threshold of the neurons which further leads to increase inmembrane resistance (Baccaglini et al., 1983).

In DRG neurons after the nerveinjury if the spontaneous action potential is negative due to hyperpolarizationand lasts long enough to activate Ih, then this Ih will contribute to facilitationof the firing discharges. Therefore the discharge frequency of spontaneouslyactive DRG neurons may be reduced by Ih inhibition through a2-adrenoceptoractivation (Yagi et al., 1998).    


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