After unilateral nerve injury, pain and increased pain sensitivity are evident on both sides of the body. This phenomenon is known as mirror image pain(MIP) [
14]. Although not all unilateral nerve injury in clinical settings will appear as mirror pain, the contralateral side often displays hyperalgesia. So in our experiment ,we did SNL model to detected both mechanical and thermal hyperalgesia. We found that unilateral nerve injury exhibited noticeable bilateral pain. Compared with the sham group, both the ipsilateral and the contralateral paw pain thresholds for thermal and mechanical hyperalgesia were significantly increased following SNL (Figure
1). We also did immunohistochemistry and western-blot to detect the expression of Nav1.7. We found compared with the sham group, Nav1.7 [
20] abnormally highly expressed in both bilateral DRG (Figure
2). Because of Nav1.7 expression is a symbol of neuron excited, high expression of Nav1.7 protein [
21] in the contralateral side may explain the increased excitability of the mirror side neurons, that is consistent with the development of mirror pain. How did the contralateral side neuron excited after unilateral nerve injury? A number of studies show that glial cells can profoundly affect the genesis and/or maintenance of pain, based on this background, we focus on the glial cells of the peripheral nervous system: Satellite glial cells (SGCs). SGCs are the glial cells in DRG and are similar to astrocytes and microglia. When SGCs become activated, they may proliferate and release substances that act as messengers to excite DRG neuron. SGCs activation occurs after nerve injury or inflammation. [
15,
16] In this experiment, immunohistochemistry showed SGCs are arranged in a layer, around the neurons. After unilateral nerve injury, both side SGCs were actived, we can see from (Figure
3) that GFAP and pJNK [
17,
18] were increased in both side DRG. So we imagined if the SGCs involved in the mechanism of MIP. We used FC to intrathecal injection, after injection we can see from (Figure
4) that the changes in SGCs can be inhibited by intrathecal injection of FC. And then after the injection we tested mechanical and thermal sensitivity, our study showed that FC reversed mechanical allodynia not only the ipsilateral but also the contralateral paw. Regardless of whether this is the explanation,the significance of our results is that an alteration of the activation of SGCs can have significant behavioral consequences. So we can draw a conclusion from this study that after SNL, SGCs become activated [
17,
18] and may release some substances ,these substances maybe the important mediators of chronic pain, as well as this experiment showed that the enhanced GFAP expression in SGCs in bilateral DRG following nerve injury. How the signal passed from the ipsilatral side to the contralateral side still remains to be answered? the answer may lie in the following two mechanisms: after neuronal injury, the pain signal will quickly reach the contralateral side SGCs from the ipsilateral side [
11,
19]. But the limitation is we still need to do more about the underlying mechanisms. SGCs activation will enhance primary neuron excitability in the form of a paracrine release in the contralateral primary neurons, thus, the contralateral pain sensitivity will increase.
Because Nav1.7 increase is the symbol of neuron excited, our results showed that Nav1.7 expression increase as well as SGC activation bilaterally after unilateral nerve injury. And then after intrathecal injection of FC, Nav1.7 expression significantly decreased in the bilateral sides. So this mean inhibition of DGC activation in DRG also suppressed the excitability of neurons and pain sensitivity, these finding suggest that SGCs play an important role in the mirror pain mechanism. Based on the above studies we can draw the following conclusion: After unilateral peripheral nerve injury, SGCs become activated, leading to an increase in the expression of Nav1.7 channels in bilateral DRG, thus producing mirror pain.