SCIENCE@home

Ivabradine, a hyperpolarization-activated channel blocker, attenuates mechanical, but not heat, hypersensitivity in hyperglycemic and normoglycemic rat models of diabetic neuropathy.

Deana Mohamed Elsayegh,Omar Tluli,Maram Elzayyat,Abdelrahman A. Karen,Layan Albarghouthi,Abdulla F Al-Emadi,Mubarak A Al-Maadid,Haya Al-Mohannadi,L. Djouhri

Published 2025 in Journal of drug targeting (Print)

ABSTRACT

Diabetic peripheral neuropathic pain (DPNP) is a debilitating complication of longstanding type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. DPNP patients experience mechanical and thermal pain hypersensitivity. Despite its clinical significance and high prevalence, treatment for DPNP remains challenging due to its unclear pathogenesis. We investigated whether hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, known to be involved in other PNP, also contribute to DPNP. We used two DPNP rat models: (a) streptozotocin (STZ) model of T1DM induced by a single STZ injection (60 mg/kg, i.p.), and (b) high fat diet-fed STZ model (HFD/STZ) of T2DM induced by feeding the rats with HFD (60% calories as fat) for 2 weeks followed by a low-dose STZ injection (35 mg/kg, i.p.). We found that: (a) diabetic (hyperglycemic) and non-diabetic (normoglycemic) STZ rats, as well as normoglycemic HFD/ZTZ rats, exhibit mechanical and heat hypersensitivity, evidenced by reduced paw withdrawal thresholds and latencies, respectively, and (b) ivabradine (10 mg/kg, i.p.), the clinically approved HCN blocker, was as effective as the positive control gabapentin in attenuating mechanical, but not heat, hypersensitivity, in both models. These findings reinforce that factors beyond hyperglycemia contribute to DPNP and highlight HCN channels as potential therapeutic targets for treating DPNP.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-79 of 79 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1