Pentraxin-3 in the Spinal Dorsal Horn Upregulates Nectin-1 Expression in Neuropathic Pain after Spinal Nerve Damage in Male Mice.

Abstract

Purpose: Neuropathic pain often originates from nerve injury or diseases of the somatosensory nervous system. However, its specific pathogenesis remains unclear. The requirement for excitatory synaptic plasticity in pain-related syndromes has been demonstrated. A recent study reported that pentraxin-3 is important in glutamatergic synaptic formation and function. Meanwhile, nectin-1 mediates synaptogenesis in neurological disorders. The present study aimed to evaluate whether pentraxin-3 and nectin-1 modulate spinal nerve damage-related neuropathic pain in male mice. Methods: L4 spinal nerve ligation (SNL) in male mice was performed to induce experimental neuropathic pain. Mechanical allodynia and heat hyperalgesia following SNL were based on paw withdrawal (PW) threshold and PW latency, respectively. Spinal pentraxin-3 levels and nectin-1 expression following SNL were examined. Pentraxin-3 and nectin-1 knockdown models were established by the shRNA method. These models were used with a recombinant pentraxin-3 cell model to investigate the underlying mechanisms of SNL. Results: The SNL operation generated persistent decreases in mechanical PW threshold and thermal PW latency, with subsequent long-lasting elevations in spinal pentraxin-3 and nectin-1 expression levels. Pentraxin-3 knockdown reduced SNL-associated neuropathic pain behaviors as well as nectin-1 amounts in the spinal dorsal horn. Nectin-1 deficiency impaired mechanical allodynia and thermal hyperalgesia following spinal nerve injury. The application of recombinant pentraxin-3 in the spinal cord triggered an acute nociception phenotype and induced spinal overexpression of nectin-1. The intrathecal knockdown of nectin-1 prevented exogenous pentraxin-3-evoked pain hypersensitivity. Conclusions: The findings suggest spinal pentraxin-3 is required for SNL-triggered neuropathic pain via nectin-1 upregulation in male mice.

• Authors: Min Zhu, Hongli Yu, Ying Sun, Wenli Yu
• Journal: Brain sciences (Brain Sci) Vol. 12 Issue 5 (May 15 2022) ISSN: 2076-3425 [Print] Switzerland
• PMID: 35625034 (Publication Type: Journal Article)