The Inhibition of Spinal Astrocytic JAK2-STAT3 Pathway Activation Correlates with the Analgesic Effects of Triptolide in the Rat Neuropathic Pain Model

Abstract

Neuropathic pain (NP) is an intractable clinical problem without satisfactory treatments. However, certain natural products have been revealed as effective therapeutic agents for the management of pain states. In this study, we used the spinal nerve ligation (SNL) pain model to investigate the antinociceptive effect of triptolide (T10), a major active component of the traditional Chinese herb Tripterygium wilfordii Hook F. Intrathecal T10 inhibited the mechanical nociceptive response induced by SNL without interfering with motor performance. Additionally, the anti-nociceptive effect of T10 was associated with the inhibition of the activation of spinal astrocytes. Furthermore, intrathecal administration of T10 attenuated SNL-induced janus kinase (JAK) signal transducers and activators of transcription 3 (STAT3) signalling pathway activation and inhibited the upregulation of proinflammatory cytokines, such as interleukin-6, interleukin-1 beta, and tumour necrosis factor-α, in dorsal horn astrocytes. Moreover, NR2B-containing spinal N-methyl D-aspartate receptor (NMDAR) was subsequently inhibited. Above all, T10 can alleviate SNL-induced NP via inhibiting the neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of T10 may be related with the suppression of spinal astrocytic JAK-STAT3 activation. Our results suggest that T10 may be a promising drug for the treatment of NP.

Spinal IL-33/ST2 Signaling Contributes to Neuropathic Pain via Neuronal CaMKII–CREB and Astroglial JAK2–STAT3 Cascades in Mice

“…36,37 In the current study, activated pSTAT3 was localized in astrocytes ( fig. 36,37 In the current study, activated pSTAT3 was localized in astrocytes ( fig.…”

Evidence for Involvement of Spinal RANTES in the Antinociceptive Effects of Triptolide, a Diterpene Triepoxide, in a Rat Model of Bone Cancer Pain

“…Similarly, Tang et al . reported the antinociceptive effects of triptolide were related with activation of spinal astrocytic JAK‐STAT3 Pathway. Our previous study showed that inhibition of the spinal RANTES expression contributes to BCP in rats .…”

Stat3 Inhibition Attenuates Mechanical Allodynia through Transcriptional Regulation of Chemokine Expression in Spinal Astrocytes

“…Recent studies demonstrated the involvement of astrocytic Jak-Stat3 pathway in the regulation of neuropathic pain [13], [14]. In rats undergoing spinal nerve ligation injury, Stat3 acts as a critical transducer that converts resting glia to reactive astrocytes for the maintenance of tactile allodynia [13].…”