Rosuvastatin attenuated the existing morphine tolerance in rats with L5 spinal nerve transection through inhibiting activation of astrocytes and phosphorylation of ERK42/44.

Abstract:

:Recent studies suggested that statins have anti-inflammatory effects beyond their lipid-lowering properties. In the present study, we sought to investigate whether rosuvastatin could alleviate morphine tolerance by attenuating the glia mediated neuroinflammation in the spinal cord. Using a rat model of L5 spinal nerve transection, on day 8 after surgery morphine (10 mg/kg) was injected subcutaneously twice daily for consecutive 10 days. On day 13, with the establishment of morphine tolerance, rosuvastatin (10 mg/kg) was given o.p. for 5 days. On day 18, lumbar spinal cord was collected immediately after last behavioral testing. The analgesic effect of morphine was determined as the percentage of maximal possible effect (%MPE) after a single morphine (4 mg/kg) injection via tail vein on day 8, 13, and 18. The MPE decreased significantly after administration of morphine to rats with neuropathy for 5 days. Rosuvastatin administration for 5 days could restore morphine antinociceptive effect significantly. Additionally, the activation of astrocytes, the phosphorylation of extracellular signal-regulated kinase 42/44 (ERK(42/44)) and the expressions of TNFα and IL-1β were inhibited significantly by rosuvastatin. Our data suggested that rosuvastatin was a promising choice to treat neuropathic pain in combination with morphine.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Li W,Li Y,Zhu S,Ji Q,Shu Y,Zhang L,Liu J

doi

10.1016/j.neulet.2014.11.003

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

314-9

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(14)00870-2

journal_volume

584

pub_type

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