Galanin stimulates neurite outgrowth from sensory neurons by inhibition of Cdc42 and Rho GTPases and activation of cofilin.

We and others have previously shown that the neuropeptide galanin modulates neurite outgrowth from adult sensory neurons via activation of the second galanin receptor; however, the intracellular signalling pathways that mediate this neuritogenic effect have yet to be elucidated. Here, we demonstrate that galanin decreases the activation state in adult sensory neurons and PC12 cells of Rho and Cdc42 GTPases, both known regulators of filopodial and growth cone motility. Consistent with this, activated levels of Rho and Cdc42 levels are increased in the dorsal root ganglion of adult galanin knockout animals compared with wildtype controls.

Characterisation of the nociceptive phenotype of suppressible galanin overexpressing transgenic mice.

The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems and is involved in many diverse biological functions. There is a substantial data set that demonstrates galanin is upregulated after injury in the DRG, spinal cord and in many brain regions where it plays a predominantly antinociceptive role in addition to being neuroprotective and pro-regenerative. To further characterise the role of galanin following nerve injury, a novel transgenic line was created using the binary transgenic tet-off system, to overexpress galanin in galaninergic tissue in a suppressible manner.

Intra-neural administration of fractalkine attenuates neuropathic pain-related behaviour.

There is increasing evidence that a number of cytokines and their receptors are involved in the processes that lead to the development and maintenance of neuropathic pain states. Here we demonstrate that levels of CX3CR1 (the receptor for the chemokine fractalkine) mRNA in lumbar dorsal root ganglia (DRG) increase 5.8-fold 7 days after sciatic nerve axotomy, and 1.

Characterization of an enhancer region of the galanin gene that directs expression to the dorsal root ganglion and confers responsiveness to axotomy.

Galanin expression markedly increases in the dorsal root ganglion (DRG) after sciatic nerve axotomy and modulates pain behavior and regeneration of sensory neurons. Here, we describe transgenic mice expressing constructs with varying amounts of sequence upstream of the murine galanin gene marked by LacZ. The 20 kb region upstream of the galanin gene recapitulates the endogenous expression pattern of galanin in the embryonic and adult intact DRG and after axotomy.

The sodium channel Nav1.5a is the predominant isoform expressed in adult mouse dorsal root ganglia and exhibits distinct inactivation properties from the full-length Nav1.5 channel.

Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with little or no expression reported postnatally. We report here the expression of Nav1.

Osteopontin expression and function within the dorsal root ganglion.

Osteopontin expression has previously been demonstrated in the adult rat dorsal root ganglion, although its function remains unclear. Here, we demonstrate, using real-time reverse transcription-polymerase (RT-PCR) chain reaction, that osteopontin mRNA expression is increased 1 and 3 weeks following sciatic nerve section (axotomy). Further, immunohistochemical staining suggests that this increase is restricted to neurons already expressing the protein.

Novel isoforms of the sodium channels Nav1.8 and Nav1.5 are produced by a conserved mechanism in mouse and rat.

The voltage-gated sodium channel Na(v)1.8 is only expressed in subsets of neurons in dorsal root ganglia (DRG) and trigeminal and nodose ganglia. We have isolated mouse partial length Na(v)1.

Transgenic overexpression of galanin in the dorsal root ganglia modulates pain-related behavior.

The neuropeptide galanin is expressed in the dorsal root ganglia (DRG) and spinal cord and is thought to be involved in the modulation of pain processing. However, its mechanisms of action are complex and poorly understood, as both facilitatory and inhibitory effects have been described. To understand further the role played by galanin in nociception, we have generated two transgenic lines that overexpress galanin in specific populations of primary afferent DRG neurons in either an inducible or constitutive manner.