Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia, phosphorylation of NMDA receptors, and cytokines expression in the thoracic spinal dorsal horn.

BACKGROUND: We previously reported that immune activation in the spinal dorsal horn contributes to pain induced by chronic pancreatitis (CP). Targeting immune response in the CNS may provide effective treatments for CP-induced pain. Recent findings demonstrate that resolvin D1 (RvD1) can potently dampen inflammatory pain. We hypothesized that intrathecal injection of RvD1 may inhibit pain of CP. METHODS: Rat CP model was built through intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). All the rats were divided into three groups: TNBS, sham, and naïve controls and were further divided for intrathecal RvD1 administration. Pain behavior of rats was tested with von Frey filaments. Anxiety-like behavior and free locomotor and exploration of rats were evaluated by open field test and elevated plus maze. Pancreatic histology was evaluated with hematoxylin and eosin staining. Phosphorylation of NMDA receptor and expression of inflammatory cytokines were examined with Western blot, real-time RT-PCR and ELISA. RESULTS: Behavioral study indicated that compared to the vehicle control, RvD1 (100 ng/kg) significantly decreased TNBS-induced mechanical allodynia at 2 h after administration (response frequencies: 49.2 ± 3.7% vs 71.3 ± 6.1%), and this effect was dose-dependent. Neither CP nor RvD1 treatment could affect anxiety-like behavior. CP or RvD1 treatment could not affect free locomotor and exploration of rats. Western blot analysis showed that compared with that of naïve group, phosphorylated NR1 (pNR1) and pNR2B in TNBS rats were significantly increased in the spinal cord (pNR1: 3.87±0.31 folds of naïve control, pNR2B: 4.17 ± 0.24 folds of naïve control). Compared to vehicle control, 10 ng/kg of RvD1 could significantly block expressions of pNR1 (2.21 ± 0.26 folds of naïve) and pNR2B (3.31 ± 0.34 folds of naïve). Real-time RT-PCR and ELISA data showed that RvD1 (10 ng/kg) but not vehicle could significantly block expressions of TNF-alpha, IL-1beta and IL-6. In addition, RvD1 did not influence pain behavior, NMDA receptor phosphorylation or cytokines production in sham-operated rats. CONCLUSIONS: These data highly suggest that RvD1 could be a novel and effective treatment for CP-induced chronic pain.

Basic fibroblast growth factor in human detrusor muscle in bladder outlet obstruction due to benign prostatic hyperplasia / 中华老年医学杂志

Objective To investigate the change of the basic fibroblast growth factor(bFGF) leve in human detrusor muscle(DM)in bladder outlet obstruction(BOO)due to benign prostatic hyperplasia(BPH)and its implication.Methods Fifty-four patients with BPH were divided into two groups:the obstructive DM stability and instability groups;and 15 men with bladder tumor who underwent operation in the same period were enrolled in the control group.The bFGF mRNA level in DM was measured by reverse transcription and polymerase chain reaction(RT-PCR)and the bFGF protein level was measured by immunohistochemical staining method.Results The bFGF-mRNA expression level of bladder smooth muscle cells was significantly lower in the control group than that in the obstructive DM stability and instability groups(all P＜0.05),but there was no significant difference between the obstructive DM stability and instability groups(P＞0.05). Conclusions The expression level of bFGF mRNA in bladder DM is elevated in BOO due to BPH,but there is little or no correlation between the increased expression of bFGF mRNA and detrusor muscle instability.