Resveratrol attenuates bone cancer pain through the inhibition of spinal glial activation and CX3CR1 upregulation

Abstract

The present study examined the effects of intrathecal use of resveratrol on pain hypersensitivities, spinal glia activation, and CX3CR1 expression in the model of bone cancer pain (BCP). The BCP model was established through intrathecally injecting Walker 256 mammary gland carcinoma cells to Sprague-Dawley rats. We found that spinal CX3CR1 expression and glial activation aggravated after inoculation. Resveratrol (i.t.) attenuated bone cancer-induced pain hypersensitivities, decreased CX3CR1 expression and glial activation in the spine in a BCP model. Resveratrol (i.t.) also attenuated mechanical allodynia resulting from intrathecally injecting fractalkine in rats. Inhibition of spinal glial activation and CX3CR1 upregulation may involve in resveratrol's analgesic effects. These findings demonstrated that resveratrol attenuated pain facilitation through inhibiting spinal glial activation and CX3CR1 upregulation in a BCP model.

Resveratrol attenuates inflammatory hyperalgesia by inhibiting glial activation in mice spinal cords

“…SIRT1 has been reported to be one of the key targeted molecule of resveratrol and involved in its multiple biological effects (46)(47)(48). Resveratrol has potential anti-oxidative and anti-inflammatory properties and has been indicated to attenuate bone cancer pain (9). Chronic treatment with resveratrol for 4 weeks decreased the serum concentration of TNF-α and attenuated diabetic neuropathic pain (10).…”

“…Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol present in grapes and red wine, which has been demonstrated to elicit a broad spectrum of biological responses in vitro and in vivo, including anticarcinogenic effects and neuroprotective and cardioprotective activities (7,8). Previous studies have indicated that resveratrol is a potential therapeutic agent to attenuate bone cancer pain (9) and diabetic neuropathic pain (10). Injection of resveratrol into the cerebral ventricles also exerts evident central antalgic effects (11).…”

Resveratrol and Malignancies

“…Using a bone cancer pain model, resveratrol was recently suggested to have analgesic effects by inhibiting the spinal glial activation and decreasing CX3CR1 [23]. …”

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

“…There is evidence suggesting that resveratrol has several beneficial biological effects, such as antioxidant, neuroprotective, antitumour, cardioprotective and anti‐inflammatory, together with antihyperalgesic activity . The antinociceptive effect of resveratrol has been demonstrated in animals with diverse types of experimental pain, arising from tissue inflammation, diabetic neuropathy, neuropathy due to spinal nerve constriction, surgery‐induced postpain, as well as from bone cancer . Thus, resveratrol may have antinociceptive actions both in acute and in chronic pain models, including cancer pain.…”

“…[6] The antinociceptive effect of resveratrol has been demonstrated in animals with diverse types of experimental pain, arising from tissue inflammation, [7,8] diabetic neuropathy, [9,10] neuropathy due to spinal nerve constriction, [11] surgery-induced postpain, [12] as well as from bone cancer. [13] Thus, resveratrol may have antinociceptive actions both in acute and in chronic pain models, including cancer pain. The antinociceptive effects of resveratrol have been reported to be caused mainly by inhibition of proinflammatory cytokines and chemokines and by promotion of the anti-inflammatory cytokine IL-10, [14,15] inhibition of COX-1 and COX-2 activity, [8,16,17] and modulation of some ligand-gated receptors in spinal cord such as glutamatergic NMDA, [18,19] purinergic P2X7, [20] and serotonergic 5-HT 3 [21] and 5-HT 7 receptors.…”