Abstract
Results of our past studies showed that hippocampal muscarinic acetylcholine receptor (mAChR)-1 mRNA and differentially expressed proteins participating in MAPK signaling were involved in electroacupuncture (EA) induced cumulative analgesia in neuropathic pain rats, but the underlying intracellular mechanism remains unknown. The present study was designed to observe the effect of EA stimulation (EAS) on hippocampal extracellular signal-regulated kinases (ERK) and p38 MAPK signaling in rats with chronic constrictive injury (CCI) of the sciatic nerve, so as to reveal its related intracellular targets in pain relief. After CCI, the thermal pain thresholds of the affected hind were significantly decreased compared with the control group (P < 0.05). Following one and two weeks' EAS of ST 36-GB34, the pain thresholds were significantly upregulated (P < 0.05), and the effect of EA2W was remarkably superior to that of EA2D and EA1W (P < 0.05). Correspondingly, CCI-induced decreased expression levels of Ras, c-Raf, ERK1 and p-ERK1/2 proteins, and p38 MAPK mRNA and p-p38MAPK protein in the hippocampus tissues were reversed by EA2W (P < 0.05). The above mentioned results indicated that EA2W induced cumulative analgesic effect may be closely associated with its function in removing neuropathic pain induced suppression of intracellular ERK and p38MAPK signaling in the hippocampus.
Highlights
It has been well-documented that patients with chronic pain often experience sustained chronic psychological and physical stress and exhibit increased anxiety, depression, and deficits in working memory [1,2,3]
Our experimental studies demonstrated that in chronic constrictive injury- (CCI-) induced neuropathic pain rats, the resultant cumulative analgesic effect of repeated electroacupuncture stimulation (EAS) of Zusanli (ST36)-Yanglingquan (GB34) is closely associated with its effects in upregulating the decreased hippocampal synaptophysin immunoactivity [16], muscarinic acetylcholine receptor-1 mRNA and choline acetyl transferase (ChAT) mRNA expression [17], and improving synaptic plasticity of nerve cells in the hippocampal CA3 region shown by electron transmission microscope [18]
Results of the present study showed that following CCI, the pain threshold of the affected paw was significantly lowered and the difference values of paw withdrawal latency (PWL) of the bilateral paws were apparently increased, peaking on day 8 after CCI, which is similar to Bennett’s and Xie’s outcomes [27]
Summary
It has been well-documented that patients with chronic pain often experience sustained chronic psychological and physical stress and exhibit increased anxiety, depression, and deficits in working memory [1,2,3]. Animal studies showed hippocampal abnormalities in animal models of chronic pain including short-term working memory dysfunction [5], recognition memory deficits [6], abnormal cytokine (IL-1β mRNA) expression [7, 8], deficits in long-term potentiation (LTP) [6], impaired enrichedenvironment neurogenesis [9], and altered synaptic plasticity [10]. Our experimental studies demonstrated that in chronic constrictive injury- (CCI-) induced neuropathic pain rats, the resultant cumulative analgesic effect of repeated electroacupuncture stimulation (EAS) of Zusanli (ST36)-Yanglingquan (GB34) is closely associated with its effects in upregulating the decreased hippocampal synaptophysin immunoactivity [16], muscarinic acetylcholine receptor (mAChR)-1 mRNA and choline acetyl transferase (ChAT) mRNA expression [17], and improving synaptic plasticity of nerve cells in the hippocampal CA3 region shown by electron transmission microscope [18].
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