Histamine upregulates Nav1.8 expression in primary afferent neurons via H2 receptors: involvement in neuropathic pain.

Abstract

INTRODUCTION:

The upregulation of Nav1.8 in primary afferents plays a critical role in the development and persistence of neuropathic pain. The mechanisms underlying the upregulation are not fully understood.

AIMS:

The present study aims to investigate the regulatory effect of histamine on the expression of Nav1.8 in primary afferent neurons and its involvement in neuropathic pain.

RESULTS:

Histamine at 10(-8) M increased the expression of Nav1.8 in cultured DRG neurons. This effect could be blocked by H2 receptor antagonist cimetidine or famotidine, but not by H1 receptor antagonist pyrilamine or dual H3 /H4 antagonist thioperamide. Peri-sciatic administration of histamine increased Nav1.8 expression in the sciatic nerve and L4/L5 DRG neurons in a dose-dependent manner, accompanied with remarkable mechanical allodynia and heat hyperalgesia in the ipsilateral hindpaw. Famotidine but not pyrilamine or thioperamide inhibited Nav1.8 upregulation and pain hypersensitivity. In addition, famotidine (40 mg/kg, i.p.) not only suppressed autotomy behavior in the rat neuroma model of neuropathic pain but also attenuated mechanical allodynia and thermal hyperalgesia following partial sciatic nerve ligation. Moreover, famotidine inhibited Nav1.8 upregulation in the neuroma and ligated sciatic nerve.

CONCLUSIONS:

Our findings indicate that histamine increases Nav1.8 expression in primary afferent neurons via H2 receptor-mediated pathway and thereby contributes to neuropathic pain. H2 receptor antagonists may potentially be used as analgesics for patients with neuropathic pain.

• Authors: Jia-Xing Yue, Ran-Ran Wang, Jie Yu, Ying-Ying Tang, Wei-Wei Hou, Guo-Dong Lou, Shi-Hong Zhang, Zhong Chen
• Journal: CNS neuroscience & therapeutics (CNS Neurosci Ther) Vol. 20 Issue 10 Pg. 883-92 (Oct 2014) ISSN: 1755-5949 [Electronic] England
• PMID: 24990156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Histamine Agonists
• Histamine H2 Antagonists
• NAV1.8 Voltage-Gated Sodium Channel
• Receptors, Histamine H2
• Scn10a protein, rat
• Famotidine
• Histamine

Topics

• Animals
• Cells, Cultured
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Famotidine (pharmacology)
• Ganglia, Spinal (cytology)
• Histamine (pharmacology, therapeutic use)
• Histamine Agonists (pharmacology, therapeutic use)
• Histamine H2 Antagonists (pharmacology)
• Hyperalgesia (drug therapy, physiopathology)
• Male
• NAV1.8 Voltage-Gated Sodium Channel (metabolism)
• Pain Measurement
• Pain Threshold (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, Histamine H2 (metabolism)
• Sciatica (pathology)
• Sensory Receptor Cells (drug effects)
• Up-Regulation (drug effects)