Abstract
ObjectiveTo explore the effects of inhibition of PI3K/Akt/mTOR signal pathway on chronic neuropathic pain (CNP) and spinal microglia in a rat model of chronic constriction injury (CCI).MethodsMale SD rats were assigned into control, sham, CCI, wortmannin, dimethyl sulfoxide (DMSO) and wortmannin-positive control groups. Paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) were recorded. qRT-PCR and Western blotting were used to detect PI3K, Akt and mTOR expressions and their phosphorylation. OX-4 expression was detected by immunohistochemistry and glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) expressions by immunofluorescence.ResultsPWMT and TWL decreased in the CCI group than in the sham group on the 7th and 14th day after operation. Compared with the control and sham groups, the CCI group showed increased PI3K, Akt and mTOR mRNA expressions and elevated PI3K, p-Akt, p-mTOR and P70S6K protein expressions. More OX-42-positive cells and higher integrated optical density (IOD) of GFAP and NGF were found in the CCI group than the sham group at the 14th day after operation. Compared with the DMSO group, the wortmannin group had higher PWMT and TWL, decreased PI3K, Akt and mTOR mRNA expressions and reduced PI3K, p-Akt, p-mTOR and P70S6K protein expressions. Less OX-42-positive cells and lower IOD of GFAP and NGF were found in the wortmannin group than the DMSO group 14th day after operation.ConclusionInhibition of PI3K/Akt/mTOR signal pathway may alleviate CNP and reduce microglia and GFAP and NGF expressions in marrow in a rat model of CCI.
Highlights
Chronic neuropathic pain (CNP) is caused by a lesion or disease of the somatosensory system, may be derived from the peripheral and central system [1]
Paw withdrawal mechanical threshold (PWMT) and thermal withdrawal latency (TWL) decreased in the constriction injury (CCI) group than in the sham group on the 7th and 14th day after operation
More OX-42-positive cells and higher integrated optical density (IOD) of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were found in the CCI group than the sham group at the 14th day after operation
Summary
Chronic neuropathic pain (CNP) is caused by a lesion or disease of the somatosensory system, may be derived from the peripheral and central system [1]. About 6 ~ 10% adults are tortured by CNP and this prevalence is significantly higher in specific conditions, such as age and obesity [2, 3]. It is frequent in infectious diseases such as HIV and leprosy and in such non-infectious conditions as diabetes and traumatic injury, considerably decreasing patient’s quality of life [4,5,6,7]. 30% ~ 40% of patients with CNP report that their pain is satisfactorily-relieved after pharmacological interventions [8] In this context, mechanism studies at cellular level on CNP progression are needed
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