Blood-borne and brain-derived microparticles in morphine-induced anti-nociceptive tolerance.

Blood-borne and brain-derived microparticles in morphine-induced anti-nociceptive tolerance. Brain Behav Immun. 2020 Jan 27;: Authors: Ruhela D, Bhopale VM, Yang M, Yu K, Weintraub E, Greenblatt A, Thom SR Abstract We hypothesized that elevations of microparticles (MPs) would occur with morphine administration to mice. Repetitive dosing to induce anti-nociceptive tolerance increases blood-borne MPs by 8-fold, and by 10-fold in deep cervical lymph nodes draining brain glymphatics. MPs express proteins specific to cells including neutrophils, microglia, astrocytes, neurons and oligodendrocytes. Interleukin (IL)-1β content of MPs increases 68-fold. IL-1β antagonist administration diminishes blood-borne and cervical lymph node MPs, and abrogates tolerance induction. Intravenous polyethylene glycol Telomer B, a surfactant that lyses MPs, and intraperitoneal methylnaltrexone also inhibit MPs elevations and tolerance. Critically, neutropenic mice do not develop anti-nociceptive tolerance, elevations of blood-borne or cervical node MPs. Immunohistochemical evidence for microglial activation by morphine does not correlated with the MPs response pattern. Neutrophil-derived MPs appear to be are required for morphine-induced anti-nociceptive tolerance. Further, patients entering treatment for opioid use disorder exhibit similar MPs elevations as do tolerant mice. PMID: 32001343 [PubMed - as supplied by publisher]
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research