Recently, α2-adrenoceptors (α2-AR) agonists have been shown to have anti-nociceptive effects and thus may become a promising therapeutic strategy for
neuropathic pain.
tizanidine is a highly selective α2-AR agonist, but the effect mechanism of
tizanidine in
neuropathic pain remains largely unknown. The present study investigated whether
tizanidine has anti-nociceptive effects in spared nerve injury (SNI) model of
neuropathic pain in rats, as well as explored the underlying molecular mechanism. We found that the rats in SNI group showed significantly higher mechanical and
thermal hyperalgesia, accompanied with increased production of proinflammatory
cytokines including interleukin-1β (IL-1β),
IL-6 and
tumor necrosis factor-α (TNF-α), as well as the activation of Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling.
PDTC, an inhibitor of TLR4/NF-κB signaling, could significantly attenuate the SNI-induced mechanical and
thermal hyperalgesia and the production of proinflammatory
cytokines. Moreover, treatment with
tizanidine also attenuated the SNI-induced mechanical and
thermal hyperalgesia, suppressed production of the proinflammatory
cytokines, and inhibited the activation of TLR4/NF-κB pathway, which could be reversed by pretreatment with BRL44408, a selective α2-AR antagonist. Taken these findings together, we demonstrated that
tizanidine has anti-nociceptive effects on
neuropathic pain via inhibiting the production of proinflammatory
cytokines through suppressing the activation of TLR4/NF-κB p65 signaling pathway.