The role of sigma-1 receptor in endoplasmic reticulum stress in neuropathic pain rats

doi:10.11958/20221491

Abstract

Abstract:

Objective To investigate the role of sigma-1 receptor (sig-1R) in endoplasmic reticulum stress in neuropathic pain (NP) rats. Methods Twenty-four SPF male SD rats with successful sheath tube were divided into the sham operation group (group S), the neuropathic pain model group (group C) and the BD1047 intervention group (group B) according to random number table, with 8 rats in each group. Chronic crush injury of sciatic nerve was used to establish NP model. On the 4th, 5th and 6th day after operation, normal saline 20 μL was injected intrathecally in the group S and the group C, and BD1047 (120 μmol/L) 20 μL was injected intrathecally in the group B once a day. The mechanical foot withdrawal response threshold (MWT) of the surgical side foot was measured on the first day before operation and on the first, 3rd, 5th and 7th day after operation. Western blot assay and immunofluorescence staining were used to detect the expression levels of sig-1R, glucose-regulated protein (BIP), activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) in dorsal root neurons (DRG). HE staining was used to observe the morphological size and pathological changes of DRG. Changes of endoplasmic reticulum in DRG were observed by scanning electron microscopy. Results Compared with the group S, intraoperative parapodum MWT was significantly decreased (P<0.05), and pathological injury and endoplasmic reticulum destruction of DRG were significantly aggravated. Expressions of sig-1R, BIP, ATF4 and CHOP were up-regulated in the group C after CCI (P<0.05). Compared with the group C, the MWT was increased on the 5th and 7th day after CCI in the group B (P<0.05), and the expressions of sig-1R, BIP, ATF4 and CHOP were down-regulated (P<0.05). The pathological injury of DRG was improved. Conclusion sig-1R are involved in the neuropathic pain in rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress in dorsal root neurons.

Key words: neuralgia, endoplasmic reticulum stress, immunoglobulin heavy chains, sigma-1 receptor, dorsal root neurons

CLC Number:

R614，R745

Figures/Tables 7

References 16

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组别	术前1 d	术后第1天	术后第3天	术后第5天	术后第7天
S组	18.5±6.4	17.1±5.7	17.8±7.0	17.7±5.0	18.7±8.1
C组	17.8±7.0	9.6±2.6^a	3.5±1.7^a	3.1±1.5^a	2.9±1.1^a
B组	17.1±5.7	9.2±1.4^a	3.4±1.5^a	7.0±1.5^ab	9.1±2.6^ab
F	0.092	11.267^**	30.215^**	44.659^**	20.159^**

组别	术前1 d	术后第1天	术后第3天	术后第5天	术后第7天
S组	18.5±6.4	17.1±5.7	17.8±7.0	17.7±5.0	18.7±8.1
C组	17.8±7.0	9.6±2.6^a	3.5±1.7^a	3.1±1.5^a	2.9±1.1^a
B组	17.1±5.7	9.2±1.4^a	3.4±1.5^a	7.0±1.5^ab	9.1±2.6^ab
F	0.092	11.267^**	30.215^**	44.659^**	20.159^**

组别	sig-1R	BIP	ATF4	CHOP
S组	0.281±0.094	0.396±0.112	0.421±0.046	0.341±0.063
C组	0.953±0.120^a	0.964±0.120^a	0.989±0.111^a	1.161±0.029^a
B组	0.726±0.043^ab	0.661±0.024^ab	0.744±0.068^ab	0.835±0.056^ab
F	41.625^**	26.319^**	37.754^**	189.762^**

组别	sig-1R	BIP	ATF4	CHOP
S组	0.281±0.094	0.396±0.112	0.421±0.046	0.341±0.063
C组	0.953±0.120^a	0.964±0.120^a	0.989±0.111^a	1.161±0.029^a
B组	0.726±0.043^ab	0.661±0.024^ab	0.744±0.068^ab	0.835±0.056^ab
F	41.625^**	26.319^**	37.754^**	189.762^**

组别	sig-1R	BIP	ATF4	CHOP
S组	0.432±0.095	0.317±0.170	0.426±0.183	0.509±0.250
C组	9.001±1.362^a	7.324±1.040^a	4.751±1.640^a	5.866±2.305^a
B组	5.392±1.619^ab	2.508±0.615^ab	1.669±0.298^ab	1.524±0.271^ab
F	74.202^**	155.288^**	31.733^**	26.717^**