Synaptotagmin 1 Is Involved in Neuropathic Pain and Electroacupuncture-Mediated Analgesic Effect

Abstract

Numerous studies have verified that electroacupuncture (EA) can relieve neuropathic pain through a variety of mechanisms. Synaptotagmin 1 (Syt-1), a synaptic vesicle protein for regulating exocytosis of neurotransmitters, was found to be affected by EA stimulation. However, the roles of Syt-1 in neuropathic pain and EA-induced analgesic effect remain unclear. Here, the effect of Syt-1 on nociception was assessed through an antibody blockade, siRNA silencing, and lentivirus-mediated overexpression of spinal Syt-1 in rats with spared nerve injury (SNI). EA was used for stimulating bilateral “Sanjinjiao” and “Zusanli” acupoints of the SNI rats to evaluate its effect on nociceptive thresholds and spinal Syt-1 expression. The mechanically and thermally nociceptive behaviors were assessed with paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different temperatures, respectively, at day 0, 7, 8, 14, and 20. Syt-1 mRNA and protein levels were determined with qRT-PCR and Western blot, respectively, and its distribution was observed with the immunohistochemistry method. The results demonstrated Syt-1 antibody blockade and siRNA silencing increased ipsilateral PWTs and PWLs of SNI rats, while Syt-1 overexpression decreased ipsilateral PWTs and PWLs of rats. EA significantly attenuated nociceptive behaviors and down-regulated spinal Syt-1 protein levels (especially in laminae I-II), which were reversed by Syt-1 overexpression. Our findings firstly indicate that Syt-1 is involved in the development of neuropathic pain and that EA attenuates neuropathic pain, probably through suppressing Syt-1 protein expression in the spinal cord.

Exosome-Mediated miR-21 Was Involved in the Promotion of Structural and Functional Recovery Effect Produced by Electroacupuncture in Sciatic Nerve Injury

“…Although peripheral nerves have a reconstitutive ability, it is difficult to fully recover nerve function after PNI. EA is not only effective in treating PNI [ 53 ] but can also be used for the treatment of neuropathic pain [ 54 ] and central nervous disease [ 55 ]. Since miRNAs are closely associated with the development of PNI [ 15 , 32 , 33 , 41 , 56 – 59 ] and nerve repair, while exosomes are valuable carriers of miRNAs [ 60 ], our study focused on exosomal delivery of miR-21 to explore the effects of EA.…”

Electroacupuncture suppresses spinal nerve ligation-induced neuropathic pain via regulation of synaptic plasticity through upregulation of basic fibroblast growth factor expression

“…15 The expression of synaptotagmin 1, a synapse-related protein, increased in rats with nerve injury, while EA decreased its expression and induced better behavioural performance. 24 Studies have also shown that the application of EA can inhibit the LTP of synaptic transmission of rats with hyperalgesia in the hind limbs. 16 The data in our study showed that the thermal and mechanical nociceptive thresholds could be increased after EA at ST36 and BL60 in the M + EA group compared with the M group.…”

Electroacupuncture Alleviates Neuropathic Pain through Regulating miR-206-3p Targeting BDNF after CCI

“…Currently, drugs used to relieve neuropathic pain, including opioids and tricyclic antidepressants, do not meet the clinical needs and commonly induce drug resistance [ 3 , 27 ]. EA, a simple and efficacious treatment method that is usually used to improve neuropathic pain, has long been the focus of researchers [ 19 , 28 ].…”