Transient Receptor Potential Channels: Multiple Modulators of Peripheral Neuropathic Pain in Several Rodent Models.

Neuropathic pain, a prevalent chronic condition in clinical settings, has attracted widespread societal attention. This condition is characterized by a persistent pain state accompanied by affective and cognitive disruptions, significantly impacting patients' quality of life. However, current clinical therapies fall short of addressing its complexity. Thus, exploring the underlying molecular mechanism of neuropathic pain and identifying potential targets for intervention is highly warranted. The transient receptor potential (TRP) receptors, a class of widely distributed channel proteins, in the nervous system, play a crucial role in sensory signaling, cellular calcium regulation, and developmental influences. TRP ion channels are also responsible for various sensory responses including heat, cold, pain, and stress. This review highlights recent advances in understanding TRPs in various rodent models of neuropathic pain, aiming to uncover potential therapeutic targets for clinical management.

Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats.

Purpose: Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca2+)-channel protein related to hyperalgesia. Dexmedetomidine (Dex) is an alpha-2 (α2) adrenoreceptor agonist that mediates intracellular Ca2+ levels to alleviate pain. However, the relationship between TRPC6 and Dex is currently unclear. We speculated that the α2 receptor agonist would be closely linked to the TRPC6 channel. We aimed to investigate whether Dex relieves neuropathic pain by the TRPC6 pathway in the dorsal root ganglia (DRG). Methods: The chronic constriction injury (CCI) model was established in male rats, and we evaluated the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of TRPC6 and Iba-1 in the DRG were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence assay. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. Results: Compared with the CCI normal saline group, both the MWT and TWL were significantly improved after 7 days of Dex administration. Results demonstrated that TRPC6 expression was increased in the DRG following CCI but was suppressed by Dex. In addition, multiple administrations of Dex inhibited the phosphorylation level of p38 mitogen-activated protein kinase and the upregulation of neuroinflammatory factors. Conclusion: The results of this study demonstrated that Dex exhibits anti-nociceptive and anti-inflammatory properties in a neuropathic pain model. Moreover, our findings of the CCI model suggested that Dex has an inhibitory effect on TRPC6 expression in the DRG by decreasing the phosphorylation level of p38 in the DRG.

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

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.