Reduction of cAMP by the adenylyl cyclase inhibitor SQ22536 inhibited, and elevation of cAMP by forskolin, dibutyryl cAMP, IBMX and rolipram increased outgrowth and extension of neurites. The cAMP-mediated effects occur via activation of protein

kinase A (PKA) and Raf inhibitor were reduced by the inhibitors, H89 and Rp-cAMP. However, cAMP elevation did not lead to Erk activation that is an essential downstream component of neurotrophin signaling. These findings provide evidence for a key role of cAMP in promoting peripheral nerve regeneration after nerve injuries and indicate that this effect is unusual in not being mediated via Erk phosphorylation. (c) 2008 Published by Elsevier Ltd.”
“Purpose: High voltage activated calcium channels have been implicated in nociceptive transmission in several animal pain models. To our knowledge this is the first study to evaluate the ability of various high voltage activated calcium channel blockers to inhibit the transmission of

noxious stimuli from the bladder at the level of the spinal cord.

Materials and Methods: The nociceptive response was measured by analyzing the visceromotor reflex FG-4592 clinical trial and cardiovascular (pressor) responses to bladder distention. The role of Cav2.2 (N-type), Cav2.1 (P/Q-type) and Cav1 (L-type) calcium channels in bladder nociceptive reflex responses was examined using omega-conotoxin-GVIA, omega-agatoxin IVA/omega-conotoxin MVIIC and verapamil (Sigma-Aldrich (TM)), respectively. Female Sprague-Dawley rats were acutely instrumented with intrathecal catheters, carotid arterial and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectric activity subsequent

to repeat phasic bladder distention at 60 mm Hg for 30 seconds at 3-minute intervals with the rats under 1% isoflurane. Drugs were administered by intrathecal. injection 2 minutes before distention and responses were recorded for 15 minutes per dose.

Results: When administered intrathecally, omega-conotoxin-GVIA and omega-conotoxin MVIIC (10 mu g/kg each) significantly attenuated reflex responses to noxious bladder distention www.selleck.cn/products/ly2874455.html to 12% and 65% of the maximal visceromotor reflex response, and to 45% and 59% of the control pressor response, respectively. However, agatoxin and verapamil were less effective.

Conclusions: The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role.”
“Increasing evidences have been accumulated during recent years suggesting a role for antidepressant drugs (ADs) as hippocampal neurogenesis enhancers, but the information about the transductional mechanisms involved in this response is very limited.