Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation

Abstract

Tissue injury is known to produce inflammation and pain. Synaptic potentiation between peripheral nociceptors and spinal lamina I neurons has been proposed to serve as a trigger for chronic inflammatory pain. Gastrodin is a main bioactive constituent of the traditional Chinese herbal medicine Gastrodia elata Blume, which has been widely used as an analgesic since ancient times. However, its underlying cellular mechanisms have remained elusive. The present study demonstrated for the first time that gastrodin exhibits an analgesic effect at the spinal level on spontaneous pain, mechanical and thermal pain hypersensitivity induced by peripheral inflammation, which is not dependent on opioid receptors and without tolerance. This analgesia by gastrodin is at least in part mediated by depressing spinal synaptic potentiation via blockade of acid-sensing ion channels. Further studies with miniature EPSCs and paired-pulse ratio analysis revealed the presynaptic origin of the action of gastrodin, which involves a decrease in transmitter release probability. In contrast, neither basal nociception nor basal synaptic transmission was altered. This study revealed a dramatic analgesic action of gastrodin on inflammatory pain and uncovered a novel spinal mechanism that could underlie the analgesia by gastrodin, pointing the way to a new analgesic for treating chronic inflammatory pain.

Retracted: Gastrodin relieves inflammation injury induced by lipopolysaccharides in MRC‐5 cells by up‐regulation of miR‐103

“…Much was known that LPS is effective in inducing inflammatory response. 22,23 This phenomenon was also appended in this 24 and neuroinflammation. 25 gastrodin may even attenuate LPS-induced acute lung injury.…”

“…For the selected examples, gastrodin is capable of relieving chronic inflammatory pain24 and neuroinflammation 25. Interestingly, pre-treating MRC-5 cells with gastrodin attenuated LPS-induced apoptosis and pro-inflammatory cytokines release.…”

Gastrodin represses hydrogen peroxide-induced oxidative stress in retinal pigment epithelial cells through p38MAPK/iNOS pathway

“…Inflammatory response of RPE was also implicated in the pathogenesis of AMD (Hytti et al, 2021), and suppression of inflammation prevented the progression of AMD (Mao et al, 2017). Since gastrodin repressed spinal synaptic potentiation and protected against chronic inflammation (Xiao et al, 2016), it can also exert an anti-inflammatory effect against H 2 O 2induced RPE in AMD, which needs to be the topic of interest in future studies. Dysregulated metabolic pathways involved in mitochondrial dysfunction and disintegration, cytoplasmic glycogen accumulation, ROS production, and autophagy function are reported to be the major contributors to AMD pathophysiology (Zhang et al, 2020).…”

Osthole alleviates neuropathic pain in mice by inhibiting the P2Y1-receptor-dependent JNK signaling pathway

“…Analgesic effects can be produced by inhibiting astrocyte activation or effectively antagonizing the painrelieving substances released by astrocyte. After peripheral nerve injury, astrocytes in the dorsal horn of spinal cord are usually activated through noxious neurotransmitters such as ATP, glutamate, SP and calcitonin-gene-related peptide released from terminals of primary neurons or pro-inflammatory factors (such as IL-1β, IL-6, TNF-α and IL-18) [29]. As an important exogenous substance, ATP activated astrocyte through P2X and P2Y family receptors (such as P2X4, P2X7 and P2Y6 in Microglia, P2Y1 and P2Y2 in neurons and P2Y1 and P2Y11 in astrocyte) [30].…”