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. 2016 Sep 1;24(5):489-94.
doi: 10.4062/biomolther.2016.006.

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

Donghua Li  1   2 , Yurong Yan  2 , Lingzhi Yu  1 , Yong Duan  3
Affiliations

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

Donghua Li et al. Biomol Ther (Seoul). .

Abstract

Neuropathic pain (NPP) is the main culprit among chronic pains affecting the normal life of patients. Procaine is a frequently-used local anesthesia with multiple efficacies in various diseases. However, its role in modulating NPP has not been reported yet. This study aims at uncovering the role of procaine in NPP. Rats were pretreated with procaine by intrathecal injection. Then NPP rat model was induced by sciatic nerve chronic compression injury (CCI) and behavior tests were performed to analyze the pain behaviors upon mechanical, thermal and cold stimulations. Spinal expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR and western blot. JAK2 was also overexpressed in procaine treated model rats for behavior tests. Results showed that procaine pretreatment improved the pain behaviors of model rats upon mechanical, thermal and cold stimulations, with the best effect occurring on the 15(th) day post model construction (p<0.05). Procaine also inhibited JAK2 and STAT3 expression in both mRNA (p<0.05) and protein levels. Overexpression of JAK2 increased STAT3 level and reversed the improvement effects of procaine in pain behaviors (p<0.01). These findings indicate that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling.

Keywords: CCI rat model; JAK2/STAT3 signaling; Neuropathic pain; Procaine.

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Figures

Fig. 1.
Fig. 1.
Behavior tests in NPP model rats upon mechanical, thermal and cold stimulations. (A) Mechanical withdrawal threshold (MWT) reflecting the reaction upon mechanical stimulation. (B) Paw withdrawal thermal latency (PWTL) reflecting the reaction upon thermal stimulation. (C) Number of withdrawal reflecting reaction upon cold stimulation. sham, rats undergone sham surgery. CCI, rats undergone sciatic nerve chronic compression injury (CCI) as the neuropathic pain (NPP) model. CCI+procaine, NPP model rats pretreated with procaine. Behavior tests are performed on 0, 5, 10, 15 and 20 d post surgery (n=3). *p<0.05, **p<0.01 and ***p<0.001 compared to sham group. #p<0.05 and ##p<0.01 compared to CCI group.
Fig. 2.
Fig. 2.
Procaine pretreatment inhibits JAK2 and STAT3 expression. (A) Relative Jak2 mRNA level detected by qRT-PCR. (B) Relative Stat3 mRNA level detected by qRT-PCR. (C) JAK2 and STAT3 protein expression detected by western blot. (D) Relative protein levels of JAK2 and STAT3 based on Western blot results. sham, rats undergone sham surgery. CCI, rats undergone sciatic nerve chronic compression injury (CCI) as the neuropathic pain (NPP) model. CCI+procaine, NPP model rats pretreated with procaine. The detection is performed on the 20th day post surgery (n=3). GAPDH is used as an internal reference. *p<0.05, **p<0.01. JAK2, Janus kinase 2. STAT3, signal transducer and activator of transcription 3.
Fig. 3.
Fig. 3.
JAK2 overexpression abrogates the effect of procaine pretreatment in NPP model rats. (A) Mechanical withdrawal threshold (MWT) reflecting the reaction upon mechanical stimulation. (B) Paw withdrawal thermal latency (PWTL) reflecting the reaction upon thermal stimulation. (C) Number of withdrawal reflecting reaction upon cold stimulation. (D) Western blot showing the expression change of JAK2 and STAT3 proteins. (E) Relative protein levels of JAK2 and STAT3 based on Western blot results. Control, neuropathic pain (NPP) model rats with no pretreatment. Procaine, NPP model rats pretreated with procaine. Procaine+blank control, NPP model rats pretreated with procaine and injected with blank vectors as the control for JAK2 overexpression. Procaine+JAK2, NPP model rats pretreated with procaine and injected with JAK2 overexpression vector. Behavior test and western blot are performed on the 15th day post surgery. GAPDH is used as an internal control in western blot. *p<0.05, **p<0.01, ***p<0.001. JAK2, Janus kinase 2. STAT3, signal transducer and activator of transcription 3.
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