Differential Expression of Long Non-Coding RNAs and Their Role in Rodent Neuropathic Pain Models

Abstract

Neuropathic pain, which is accompanied by an unpleasant sensation, affects the patient's quality of life severely. Considering the complexity of the neuropathic pain, there are huge unmet medical needs for it while current effective therapeutics remain far from satisfactory. Accordingly, exploration of mechanisms of neuropathic pain could provide new therapeutic insights. While numerous researches have pointed out the contribution of sensory neuron-immune cell interactions, other mechanisms of action, such as long non-coding RNAs (lncRNAs), also could contribute to the neuropathic pain observed in vivo. LncRNAs have more than 200 nucleotides and were originally considered as transcriptional byproducts. However, recent studies have suggested that lncRNAs played a significant role in gene regulation and disease pathogenesis. A substantial number of long non-coding RNAs were expressed differentially in neuropathic pain models. Besides, therapies targeting specific lncRNAs can significantly ameliorate the development of neuropathic pain, which reveals the contribution of lncRNAs in the generation and maintenance of neuropathic pain and provides a new therapeutic strategy. The primary purpose of this review is to introduce recent studies of lncRNAs on different neuropathic pain models.

Keywords: long non-coding RNAs; microarray analysis; neuropathic pain; pain model; treatment.

Figure 1

The major animal models of neuropathic pain. (A) The CCI model loosely ties the unilateral sciatic nerve below the mid-femur region with four chromic gut ligatures. It shows behavioral signs of spontaneous pain and hyperalgesia (thermal and tactile allodynia) and duration of pain signs persist over 2 months. (B) L5 and L6 spinal nerves of SNL model are tied unilaterally and closely at the distal side of dorsal root ganglia. It could indicate allodynia and hyperalgesia and last for at least 4 months. (C) DNP model was established by a single i.p. injection of streptozocin (STZ) and it induces thermal and mechanical hyperalgesia for 2–3 weeks. (D) In SNI model, the common peroneal and tibial nerves was ligated and axotomized, but sural nerve remained intact. Paw withdrawal threshold after SNI is significantly lower than sham group and hyperpathia lasts for at least 1 month.

Figure 2

Differentially expressed lncRNA in differential neuropathic pain models. ↑: up-regulation; ↓: down-regulation. Differential shapes of lncRNAs denote gene symbol without biological meaning. Center works represent different models of neuropathic pain.