The etiological changes of acetylation in peripheral nerve injury-induced neuropathic hypersensitivity

Abstract

Neuropathic pain is a common chronic pain condition with mechanisms far clearly been elucidated. Mounting preclinical and clinical studies have shown neuropathic pain is highly associated with histone acetylation modification, which follows expression regulation of various pain-related molecules such as mGluR1/5, glutamate aspartate transporter, glutamate transporter-1, GAD65, Na_v1.8, Kv4.3, μ-opioid receptor, brain-derived neurotrophic factor, and certain chemokines. As two types of pivotal enzymes involved in histone acetylation, histone deacetylases induce histone deacetylation to silence gene expression; in contrast, histone acetyl transferases facilitate histone acetylation to potentiate gene transcription. Accordingly, upregulation or blockade of acetylation may be a promising intervention direction for neuropathic pain treatment. In fact, numerous animal studies have suggested various histone deacetylase inhibitors, Sirt (class III histone deacetylases) activators, and histone acetyl transferases inhibitors are effective in neuropathic pain treatment via targeting specific epigenetic sites. In this review, we summarize the characteristics of the molecules and mechanisms of neuropathy-related acetylation, as well as the acetylation upregulation and blockade for neuropathic pain therapy. Finally, we will discuss the current drug advances focusing on neuropathy-related acetylation along with the underlying treatment mechanisms.

Keywords: Nerve injury; acetylation; etiology; neuropathic pain; outcomes.