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Papers of the Week

Papers: 21 Jan 2023 - 3 Feb 2023

2023 Jan 28

Mol Ther

Long-term reversal of chronic pain behavior in rodents through elevation of spinal agmatine.


Peterson CD, Waataja JJ, Kitto KF, Erb S, Verma H, Schuster DJ, Churchill CC, Riedl MS, Belur LR, Wolf DA, McIvor SR, Vulchanova L, Wilcox GL, Fairbanks CA
Mol Ther. 2023 Jan 28.
PMID: 36710491.


Chronic pain remains a significant burden worldwide while treatments are often limited by safety or efficacy. The decarboxylated form of L-arginine, agmatine, antagonizes N-methyl-D-aspartate receptors, inhibits nitric oxide synthase, and reverses behavioral neuroplasticity. We hypothesized that expressing the proposed synthetic enzyme for agmatine in the sensory pathway could reduce chronic pain without motor deficits. Intrathecal delivery of an adeno-associated viral vector carrying the gene for arginine decarboxylase prevented the development of chronic neuropathic pain as induced by spared nerve injury in mice and rats and persistently reversed established hypersensitivity 266 days post-injury. Spinal long-term potentiation was inhibited by both exogenous agmatine and AAV-hADC vector pre-treatment but was enhanced in rats treated with anti-agmatine immunoneutralizing antibodies. These data suggest that endogenous agmatine modulates the neuroplasticity associated with chronic pain. Development of approaches to access this inhibitory control of neuroplasticity associated with chronic pain may yield important non-opioid pain-relieving options.