Liver X Receptor β Is Involved in Formalin-Induced Spontaneous Pain

Abstract

Increasing evidence indicates that the liver X receptor(LXR) β modulates inflammatory pain. However, the molecular mechanisms through which LXRβ modulates pain are unclear. Here, we found that LXRβ-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXRβ knockout (KO) mice compared with the WT controls. In addition, LXRβ deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1β ,TNF-α) as well as NFκB in the formalin-injected paw were elevated by the loss of LXRβ. Taken together, these data indicate that LXRβ is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.

Intrathecally Administered Apelin-13 Alleviated Complete Freund’s Adjuvant-Induced Inflammatory Pain in Mice

“…In the spinal cord, Fos expression was one of the long-term intracellular events, which was described as an indirect marker of nociceptive processes ( Chapman and Besson, 1997 ). Our result demonstrated CFA injection up-regulated Fos mRNA expression in lumbar spinal cord and increased Fos-positive staining of laminae III and IV/V of the dorsal horn compared with the vehicle control, which was consistent with previous studies ( Bao et al, 2017 ; Choi et al, 2018 ). In this study, we found that i.t.…”

“…Each spinal cord was instantly removed, fixed with the above fixative overnight, and then embedded in paraffin. Transverse sections (5 μm thick) of the L4/5 spinal cord were cut using a vibratome (Leica Biosystems, Nussloch, Germany), and stained as previously described ( Bao et al, 2017 ). Serial sections were blocked in 10% normal goat serum at room temperature for 1 h. A rabbit anti-c-Fos antibody (1:100, Abcam Inc., Burlingame, CA, USA) was applied and sections were incubated overnight at room temperature.…”

Epothilone B Benefits Nigral Dopaminergic Neurons by Attenuating Microglia Activation in the 6-Hydroxydopamine Lesion Mouse Model of Parkinson’s Disease

“…The optical fractionator method was then used to estimate the total number of TH + cells in the SNc of each animal. TH + fibers in the striatum were quantified according to optical density with KS300 software (AxioVision) as previously described (Bao et al, 2017 ). The relative optical density of each group was obtained by subtracting the background optical density and was normalized to that of the sham group.…”

Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule Stabilization After Intracerebral Hemorrhage

“…TH-positive fibers in the basal ganglia surrounding the lesion and the ipsilateral SN pars reticulata as well as BDApositive fibers in the striatum were quantitated according to optical density with KS300 software (AxioVision), as described by Bao et al 27 The relative optical density was obtained by subtracting the background optical density from the measured optical density. Then, the relative optical density of each group was normalized to that of the sham group and statistically analyzed using SPSS software (IBM Corp).…”