Resveratrol enhances IL-4 receptor-mediated anti-inflammatory effects in spinal cord and attenuates neuropathic pain following sciatic nerve injury

Abstract

Resveratrol has been showed to relieve neuropathic pain through its anti-inflammatory effects on the peripheral nerve system. However, it is not clear whether resveratrol, especially when administered systemically, is effective in alleviating the peripheral neuropathy-induced imbalance between pro-and anti-inflammatory responses in the central nervous system. To test this, we used a rat neuropathic pain model resulting from chronic constriction injury of the sciatic nerve. Resveratrol (200 mg/kg) or vehicle (dimethylsulfoxide) were administered intraperitoneally once daily for 14 consecutive days after chronic constriction injury. We found that resveratrol attenuated mechanical allodynia and thermal hyperalgesia in rats with chronic constriction injury. After 14 days of resveratrol treatment, expression of several anti-inflammatory cytokine receptors, including IL-1RA and IL-1R2, was increased in the dorsal spinal cord of rats with chronic constriction injury, and IL-4Ra was increased in dorsal spinal cord neurons. Knockdown of IL-4Ra in a neuronal cell line reversed the resveratrol-induced upregulation of IL-1RA and IL-1R2. These results indicate that resveratrol enhances IL-4 receptor-mediated anti-inflammatory responses in the spinal cord and thus might contribute to the alleviation of central sensitization following peripheral nerve injury.

Resveratrol alleviates nuclear factor‐κB‐mediated neuroinflammation in vasculitic peripheral neuropathy induced by ischaemia–reperfusion via suppressing endoplasmic reticulum stress

“…Resveratrol has been reported to modulate NF‐κB‐mediated transcription of inflammatory proteins in lipopolysaccharide‐induced neuroinflammation via inhibition of NF‐κB translocation, IκB phosphorylation, and pro‐inflammatory cytokine production . Resveratrol has also been shown to inhibit pro‐inflammatory cytokines, including TNF‐α and IL‐1β, in the peripheral nerve system and relieves animals suffering from neuropathic pain . Data from the molecular study support the concept that resveratrol modulates NF‐κB‐medicated neuroinflammation in VPN induced by IR through inhibiting the IκB phosphorylation and NF‐κB translocation.…”

“…41 Resveratrol has also been shown to inhibit pro-inflammatory cytokines, including TNF-α and IL-1β, in the peripheral nerve system and relieves animals suffering from neuropathic pain. 18,19 Data from the molecular study support the concept that resveratrol modulates NF-κB-medicated neuroinflammation in VPN induced by IR through inhibiting the IκB phosphorylation and NF-κB translocation.…”

“…Moreover, resveratrol has been reported to exert neuroprotective effects against experimental models of stroke, traumatic brain injury, spinal cord injury, as well as peripheral nerve injury . Recent studies revealed that resveratrol may attenuate neuropathic pain associated with peripheral neuropathies through its anti‐inflammatory activity …”

“…16,17 Recent studies revealed that resveratrol may attenuate neuropathic pain associated with peripheral neuropathies through its anti-inflammatory activity. 18,19 Currently, the question of whether resveratrol has a protective role against neuropathic pain and impaired peripheral nerve function associated with VPN has not yet been studied. Based on the anti-inflammatory property of resveratrol, we hypothesized that resveratrol may alleviate VPN induced by IR through suppressing the activation of NF-κB signalling in the sciatic nerve.…”

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

“…To the best of our knowledge, this is the first study exploring the role of BRD4 in inflammatory response regulation after SCI and describing a BRD4 inhibitor capable of suppressing inflammatory response via negatively modulating NF-κB and MAPK signalling pathways (Figure 8).BET family such as BRD4 are reported to activate many inflammation-related genes,26 and inflammation blocks functional recovery and aggravates neuropathic paresthesia in damaged spinal cord 27,28. To the best of our knowledge, this is the first study exploring the role of BRD4 in inflammatory response regulation after SCI and describing a BRD4 inhibitor capable of suppressing inflammatory response via negatively modulating NF-κB and MAPK signalling pathways (Figure 8).BET family such as BRD4 are reported to activate many inflammation-related genes,26 and inflammation blocks functional recovery and aggravates neuropathic paresthesia in damaged spinal cord 27,28.…”