Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat

Jiang, Yuqiu; Xing, Guo-Gang; Wang, Sheng-Lan; Tu, Huiyin; Chi, Ye-Nan; Li, Jie; Liu, Fengyu; Han, Ji-Sheng; Wan, You

doi:10.1016/j.pain.2007.10.011

Cited by 101 publications

(117 citation statements)

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“…When ZD7288 was given to the neuropathic pain models either intraperitoneally [27], or intrathecally [55], or perineuronally to the injured sciatic nerve [51], or intraplantarly to the injured hind paw [46], or topically to the injured DRG (our unpublished data), significant analgesic effects were observed with no disturbance in motor function (Fig. 3b-d).…”

Section: Role Of I H In Neuropathic Painmentioning

confidence: 96%

“…We found that HCN1 positive staining can be clearly found along the axolemma of myelinated axons, HCN2-ir was seen along the membrane of unmyelinated axons in a segmental pattern. Nevertheless, the expression of HCN channels in the axon is indeed more limited than that in DRG and central nervous systems [51].…”

Section: Distribution Of Hcn Channels In the Pathway Of Pain Transmismentioning

confidence: 99%

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Characteristics of HCN Channels and Their Participation in Neuropathic Pain

Jiang

Sun

et al. 2008

Neurochem Res

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Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. A number of ion channels are considered to contribute to the neuronal hyperexcitability. Here, we particularly concentrate on an interesting ion channel, hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain.

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Section: Role Of I H In Neuropathic Painmentioning

confidence: 96%

Section: Distribution Of Hcn Channels In the Pathway Of Pain Transmismentioning

confidence: 99%

Characteristics of HCN Channels and Their Participation in Neuropathic Pain

Jiang

Sun

et al. 2008

Neurochem Res

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“…In this respect, the efficacy of HCN blockers has been demonstrated in various neuropathic pain models (Dalle and Eisenach, 2005;Jiang et al, 2008;Takasu et al, 2010), suggesting a prominent role of these channels in maintaining chronic pain state. In 2011, Descoeur and collaborators reported an increase in HCN1 mRNA levels in DRG from oxaliplatin (OXA)-treated mice.…”

Section: Hcn Channels In Pain Transmissionmentioning

confidence: 99%

Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy

et al. 2018

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a b s t r a c tChemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies. Neuropathies are associated to aberrant excitability of DRG neurons due to the alteration in the expression or function of a variety of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are overexpressed in inflammatory and neuropathic pain states, and HCN blockers have been shown to reduce neuronal excitability and to ameliorate painful states in animal models. However, HCN channels are critical in cardiac action potential, and HCN blockers used so far in pre-clinical models do not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we show an HCN current gain of function in DRG neurons from oxaliplatin-treated rats. Biochemically, we observed a downregulation of HCN2 expression and an upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion, this study strengthens the evidence for a disease-specific role of HCN1 in CIPN, and proposes HCN1-selective inhibitors as new-generation pain medications with the desired efficacy and safety profile.

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“…), the left L5 spinal nerve distal to the dorsal root ganglion (DRG) was tightly ligated with 4-0 silk sutures as described by Kim and Chung [13][14][15] . Animals were allowed to recover for 7 d before electrophysiological recordings.…”

Section: Snl Proceduresmentioning

confidence: 99%

Electrophysiological properties of spinal wide dynamic range neurons in neuropathic pain rats following spinal nerve ligation

Liu

Cai

et al. 2011

Neurosci. Bull.

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Objective The present study aimed to investigate the electrophysiological properties of wide dynamic range (WDR) neurons in spinal dorsal horn of rats with neuropathic pain induced by lumber 5 (L5) spinal nerve ligation (SNL) in a large size of samples. Methods Adult Sprague-Dawley rats were divided into normal and SNL groups. Electrophysiological technique was used to record the characteristics of WDR neurons in the spinal dorsal horn. Results Compared with the WDR neurons in normal rats, the WDR neurons in SNL rats showed an increase in excitability, manifested by an enlargement of the receptive field size, an increase in the proportion of neurons that exhibited spontaneous activities, decreases in the Cresponse threshold and latency, and an increase in the C-response duration. In addition, the numbers of A  -and C-fiberevoked discharges were smaller in SNL rats than in normal rats. Conclusion The excitability of spinal WDR neurons increased in rats with neuropathic pain induced by L5 SNL. The increase in excitability of WDR neurons may contribute to the development of neuropathic pain.

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Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat

Cited by 101 publications

References 50 publications

Characteristics of HCN Channels and Their Participation in Neuropathic Pain

Characteristics of HCN Channels and Their Participation in Neuropathic Pain

Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy

Electrophysiological properties of spinal wide dynamic range neurons in neuropathic pain rats following spinal nerve ligation

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