Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons.

Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel.

Local translation of TC10 is required for membrane expansion during axon outgrowth.

The surface of developing axons expands in a process mediated by the exocyst complex. The spatio-temporal regulation of the exocyst is only partially understood. Here we report that stimulated membrane enlargement in dorsal root ganglion (DRG) axons is triggered by intra-axonal synthesis of TC10, a small GTPase required for exocyst function.

Paclitaxel alters the evoked release of calcitonin gene-related peptide from rat sensory neurons in culture.

Peripheral neuropathy (PN) is a debilitating and dose-limiting side effect of treatment with the chemotherapeutic agent, paclitaxel. Understanding the effects of paclitaxel on sensory neuronal function and the signaling pathways which mediate these paclitaxel-induced changes in function are critical for the development of therapies to prevent or alleviate the PN. The effects of long-term administration of paclitaxel on the function of sensory neurons grown in culture, using the release of the neuropeptide calcitonin gene-related peptide (CGRP) as an endpoint of sensory neuronal function, were examined.

Local antinociception induced by endothelin-1 in the hairy skin of the rat's back.

Unlabelled: Subcutaneous injection of endothelin-1 (ET-1) into the glabrous skin of the rat's hind paw is known to produce impulses in nociceptors and acute nocifensive behavioral responses, such as hind paw flinching, and to sensitize the skin to mechanical and thermal stimulation. In this report, we show that in contrast to the responses in glabrous skin, ET-1 injected subcutaneously into rat hairy skin causes transient antinociception. Concentrations of 1 to 50 microM ET-1 (in 0.

The c-kit signaling pathway is involved in the development of persistent pain.

Protein kinase signal transduction pathways play critical roles in regulating nociception. Here we show that c-kit, a tyrosine kinase receptor, is expressed in lamina I and II layer of the dorsal horn. Moreover, the superficial c-kit(+) fibers originate from the dorsal root ganglion, and c-kit in lamina II inner layer comes from intrinsic expression of the spinal cord.