The administration of COX-2 inhibitors, celecoxib and MPO-0029, significantly alleviated LSS-induced chronic mechanical allodynia and inhibited the mRNA expression of inflammatory mediators such as tnf-α, Il-1β, il-6, and inos.
Furthermore, the enhanced expressions of TLR4 and p-p65 were also detected in plantar tissues around the incision, which was observed starting at 2 h and lasting until the third day after surgery.Prior intrathecal (i.t.) injections of TAK-242 (a TLR4-specific antagonist) or 4',6-diamidino-2-phenylindole-dihydrochloride (PDTC, a nuclear factor-kappa B activation inhibitor) dose dependently alleviated plantar incision-induced mechanical allodynia and thermal hyperalgesia and inhibited the increased expressions of p-p65, tumor necrosis factor-alpha, and interleukin-1 beta in DRG.
Further, treatment with PD168393 attenuated mechanical allodynia in CYP-induced cystitis and inhibited microglia activation, leading to decreased production of IL-1β.
Spinal Interleukin-1β Inhibits Astrocyte Cytochrome P450c17 Expression Which Controls the Development of Mechanical Allodynia in a Mouse Model of Neuropathic Pain.
Leishmania amazonensis-induced chronic inflammation with significant increase in mechanical hyperalgesia, MPO and NAG activity, and IL-1β, TNF-α and IL-6 production in the paw skin.Glucantime (10 mg/kg, i.p.) inhibited L. amazonensis-induced mechanical hyperalgesia and IL-1β and IL-6 cytokines productions.
Intraperitoneal administration of PII remarkably reversed the CCI-induced mechanical allodynia and thermal hyperalgesia and reduced the mRNA and protein levels of IL-1β, IL-6, and TNF-α in the spinal cord.
Specifically, microglial Panx1-mediated release of the proinflammatory cytokine interleukin-1β (IL-1β) induced mechanical allodynia in the MIA-injected hindlimb.
Systemic (subcutaneous, s.c.) administration of TC-2559 during either the early (days 0-3) or middle/late (days 7-10) phase of PSL improved mechanical allodynia.Moreover, local (perineural, p.n.) administration of TC-2559 and sazetidine A, a partial agonist for α4β2 nAChR, during either the early or middle phase of PSL improved mechanical allodynia.However, p.n. administration of sazetidine A during the late (days 21-24) phase did not show the attenuating effect, whereas p.n. administration of TC-2559 during this phase relieved mechanical allodynia.Most importantly, p.n. administration of TC-2559 significantly suppressed morphological activation of Iba1<sup>+</sup> microglia and decreased the upregulation of inflammatory microglia-dominant molecules, such as CD68, interferon regulatory factor 5, and IL-1β in the SDH after PSL.
Intrathecal injection of IL-1β induced mechanical allodynia and Cav2.2 upregulation in bilateral L4-6 DRGs of naïve rats, whereas injection of IL-10 substantially prevented mechanical allodynia and Cav2.2 upregulation in L4 DRGs in L5-SNL rats.
The side that received treatment had lower concentrations of TNF-α and IL-1β in the sciatic nerve branches and sciatic nerve trunk; this result may have been related to the alleviation of mechanical allodynia.
Additionally, mRNA levels of inflammation related molecules including IL-1β, IL-6, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) and CD16, were increased after cisplatin treatment.Intraperitoneal (i.p.) or intrathecal (i.t.) injection with minocycline both alleviated cisplatin-induced mechanical allodynia and sensory deficits, and prevented IENFs loss.
Intrathecal short-hairpin RNA (shRNA)-IRF3 attenuated mechanical allodynia and thermal hyperalgesia in CCI rats, as well as inhibited the production of TNF-α and IL-1β in the DRG of CCI rats.
In the CFA model, eucalyptol strongly attenuated oedema and mechanical allodynia and reduced levels of inflammatory cytokines (IL-1β, TNF-α and IL-6), effects comparable with those of ibuprofen.
The results showed that SNI produced mechanical allodynia and depressive-like behaviors, and also increased the expressions of microglia markers (Iba1, CD11b) and M1 markers (CD68, iNOS, IL-1β, TNF-α, and 8-OH-dG) in the prefrontal cortex.
Spinal blocking EphB1 receptor activation in the late phase after STZ injection significantly suppressed the established mechanical allodynia as well as activation of the astrocytes and microglial cells and activity of TNF-α and IL-1β.
These results demonstrate that spinal IL-1β suppresses Cx43 expression and astrocyte activation during the early phase of CA-induced inflammation resulting in the delayed onset of contralateral MA.
Acute oral treatment with ethanol 24h prior to LPS administration did not alter mechanical hyperalgesia.The i.c.v. injection of IL-1β (1-10ng) also induced dose-related mechanical hyperalgesia in the right hindpaw in non-exposed animals.
Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-kappaB p65 and production of proinflammatory cytokines (e.g., TNF-alpha and IL-1 beta).