There are many reports about natural products relieving
neuralgia.
Osthole is the main component of Angelica biserrata Yuan et Shan, a natural product that treats
rheumatism through the elimination of
inflammation and the alleviation of
pain that has a long history in the clinic. The
analgesic mechanism of
osthole is complicated and confusing. Astrocytes have attracted increasing attention from
pain researchers. Inhibitors targeting astrocytes are thought to be promising treatments for
neuropathic pain. Whether
osthole can alleviate
neuropathic pain through astrocytes has not been elucidated in detail. In this study, CCI surgery was used to establish the
neuropathic pain model in mice. The CCI mice were treated with
osthole (5, 10, or 20 mg/kg/day) for 14 days in vivo.
Mechanical allodynia and heat
hyperalgesia were measured to evaluate the
therapeutic effect of
osthole. In mechanism research, the activation of astrocytes; the
protein expression of P2Y1R and p-JNK in astrocytes; the release of inflammatory factors; the variations in mEPSPs and eEPSPs; and the levels of GluA1, GluN2B, p-ERK, p-CREB and c-Fos in neurons were observed. The P2Y1R inhibitor
MRS2179 and the p-JNK inhibitor
SP600125 were used to demonstrate how
osthole works in
neuropathic pain. In addition, astrocytes and neurons were used to estimate the direct effect of
osthole on astrocyte-neuron interactions and signal transmission in vitro. Our findings suggest that
osthole treatment obviously relieved
mechanical allodynia and heat
hyperalgesia in CCI mice. P2Y1R is involved in CCI-induced
pain hypersensitivity, and P2Y1R is required for
osthole-induced p-JNK downregulation in the spinal cord.
Osthole inhibited astrocyte activation and reduced inflammatory factor expression. After
osthole treatment, mEPSP frequency and eEPSP amplitude were decreased in spinal lamina I-II neurons. Downstream signaling molecules such as pGluA1, pGluN2B, p-ERK, p-CREB and c-Fos were also reduced very quickly in
osthole-treated neuralgic mice. Our conclusion is that
osthole alleviates
neuropathic pain in mice via the P2Y1-receptor-dependent JNK signaling pathway in spinal astrocytes, and
osthole could be considered a potential
pharmacotherapy to alleviate
neuropathic pain.