Glucagon-like peptide-1 receptor has anti-apoptotic, anti-inflammatory, and
neuroprotective effects. It is now recognized that the occurrence and development of
chronic pain are strongly associated with anti-inflammatory responses; however, it is not clear whether
glucagon-like peptide-1 receptor regulates
chronic pain via anti-inflammatory mechanisms. We explored the effects of
glucagon-like peptide-1 receptor on nociception, cognition, and
neuroinflammation in
chronic pain. A rat model of
chronic pain was established using left L5 spinal nerve
ligation. The
glucagon-like peptide-1 receptor agonist
exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve
ligation. Electrophysiological examinations showed that,
after treatment with
exendin-4, paw withdrawal frequency of the left limb was significantly reduced, and
pain was relieved. In addition, in the Morris water maze test, escape latency increased and the time to reach the platform decreased following
exendin-4 treatment. Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus, as well as an increase in the expression of
tumor necrosis factor alpha,
interleukin 1 beta, and
interleukin 6. All of these effects could be reversed by
exendin-4 treatment. These findings suggest that
exendin-4 can alleviate
pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the
glucagon-like peptide-1 receptor pathway. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China (approval No. WDRM 20171214) on September 22, 2017.