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Papers of the Week

Papers: 16 Dec 2023 - 22 Dec 2023


Neurobiol Pain



Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain.


Joyce RL, Tibbs GR, David Warren J, Costa CJ, Aromolaran K, Lea Sanford R, Andersen OS, Li Z, Zhang G, Willis DE, Goldstein PA


2,6-di–butylphenol (2,6-DTBP) ameliorates mechanical allodynia and thermal hyperalgesia produced by partial sciatic nerve ligation in mice, and selectively inhibits HCN1 channel gating. We hypothesized that the clinically utilized non-anesthetic dimerized congener of 2,6-DTBP, probucol (2,6-di–butyl-4-[2-(3,5-di–butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol), would relieve the neuropathic phenotype that results from peripheral nerve damage, and that the anti-hyperalgesic efficacy would correlate with HCN1 channel inhibition A single oral dose of probucol (800 mg/kg) relieved mechanical allodynia and thermal hyperalgesia in a mouse spared-nerve injury neuropathic pain model. While the low aqueous solubility of probucol precluded assessment of its possible interaction with HCN1 channels, our results, in conjunction with recent data demonstrating that probucol reduces lipopolysaccharide-induced mechanical allodynia and thermal hyperalgesia, support the testing/development of probucol as a non-opioid, oral antihyperalgesic albeit one of unknown mechanistic action.