Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons

Verge, Valerie M. K.; Richardson, P. M.; Wiesenfeld-Hallin, Z.; Hökfelt, Tomas

doi:10.1523/jneurosci.15-03-02081.1995

Cited by 370 publications

(228 citation statements)

References 82 publications

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“…Interestingly, chronic NGF administration leads to a normalization of CCK expression in neuropathic rats (Verge et al, 1995), which is known to be upregulated after nerve injury (Hökfelt et al, 1994). Consistent with this, our laboratory has also shown that NGF administration can protect against the decreased opioid analgesia seen with nerve injury, and that intrathecal morphine efficacy can also be augmented by a CCK-B antagonist in naïve animals chronically treated anti-NGF antibodies (Cahill et al, 2003b).…”

Section: Introductionsupporting

confidence: 62%

“…administration of NGF in neuropathic animals leads to a decrease in neurons that express CCK (Verge et al, 1995), and that anti-NGF administration results in altered neuropeptide expression that resembles axotomy (Christensen & Hulseboch, 1997;Shadiack et al, 2001). Further, while there have been several reports suggesting that CCK-8 may regulate NGF synthesis in inflammation, normal conditions, and possibly neuropathy (Tirassa et al, 1998;Manni et al, 2002;Manni et al, 2003), there has only been one report linking a regulation of CCK by NGF in an inflammatory animal model.…”

Section: Discussionmentioning

confidence: 99%

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The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

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Animal models of inflammatory pain are characterized by the release of inflammatory mediators such as cytokines and neurotrophic factors, and enhanced analgesic sensitivity to opioids. In this study, we examine the mechanisms underlying this effect, in particular the roles of cholecystokinin (CCK) and nerve growth factor (NGF), in an animal model of central nervous system (CNS) inflammation induced by spinal administration of lipopolysaccharide (LPS). Although spinal administration of LY-225910 (25 ng), a CCK-B antagonist, enhanced morphine analgesia in naïve rats, it was unable to do so in LPS-treated animals. Conversely, spinal CCK-8S administration (1 ng) decreased morphine analgesia in LPS-treated rats, but not in naıve animals. Further, spinal anti-NGF (3 mg) was able to reduce morphine analgesia in LPS-treated rats, but not in naïve animals, an effect that was reversed by spinal administration of LY-225910. While CCK-8S concentration was increased in spinal cord extracts of LPS animals as compared to controls, morphine-induced spinal CCK release in the extracellular space, as measured by in-vivo spinal cord microdialysis was inhibited in LPS animals as compared to controls, and this was reversed by anti-NGF pretreatment. Finally, chronic spinal administration of b-NGF (7 mg/day) for 7 days enhanced spinal morphine analgesia, possibly by mimicking a CNS inflammatory state. We suggest that in intrathecally LPS-treated rats, spinal CCK release is altered resulting in enhanced morphine analgesia, and that this mechanism may be regulated to an important extent by NGF.

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Section: Introductionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

et al. 2009

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“…At the conclusion of the experiments, rats were killed, and tissue was dissected and processed for in situ hybridization and/or immunohistochemistry as described below. Previous studies have demonstrated a lack of influence ipsilateral and contralateral to injury when vehicle is infused intrathecally (Verge et al, 1989a;Verge et al, 1995;Jongsma Wallin et al, 2001;WilsonGerwing et al, 2005).…”

Section: Animal Surgerymentioning

confidence: 98%

Neurotrophin-3 significantly reduces sodium channel expression linked to neuropathic pain states

Wilson-Gerwing

Stucky

McComb

et al. 2008

Experimental Neurology

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Neuropathic pain resulting from chronic constriction injury (CCI) is critically linked to sensitization of peripheral nociceptors. Voltage gated sodium channels are major contributors to this state and their expression can be upregulated by nerve growth factor (NGF). We have previously demonstrated that neurotrophin-3 (NT-3) acts antagonistically to NGF in modulation of aspects of CCI-induced changes in trkA-associated nociceptor phenotype and thermal hyperalgesia. Thus, we hypothesized that exposure of neurons to increased levels of NT-3 would reduce expression of Na v 1.8 and Na v 1.9 in DRG neurons subject to CCI. In adult male rats, Na v 1.8 and Na v 1.9 mRNAs are expressed at high levels in predominantly small to medium size neurons. One week following CCI, there is reduced incidence of neurons expressing detectable Na v 1.8 and Na v 1.9 mRNA, but without a significant decline in mean level of neuronal expression, and similar findings observed immunohistochemically. There is also increased accumulation/redistribution of channel protein in the nerve most apparent proximal to the first constriction site. Intrathecal infusion of NT-3 significantly attenuates neuronal expression of Na v 1.8 and Na v 1.9 mRNA contralateral and most notably, ipsilateral to CCI, with a similar impact on relative protein expression at the level of the neuron and constricted nerve. We also observe reduced expression of the common neurotrophin receptor p75 in response to CCI that is not reversed by NT-3 in small to medium sized neurons and may confer an enhanced ability of NT-3 to signal via trkA, as has been previously shown in other cell types. These findings are consistent with an analgesic role for NT-3.

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“…Second, neurotrophins can reverse many of the changes associated with axotomy in both the neonate and the adult, including cell loss (Eriksson et al, 1994), changes in neurochemistry (Verge et al, 1990a(Verge et al, , 1992(Verge et al, , 1995Ohara et al, 1995;Sterne et al, 1998), physiology (Munson et al, 1997), and central connectivity (Bennett et al, 1996). And, not least of all, neurotrophic factors promote sensory neurite outgrowth in vitro (Gavazzi et al, 1999;Lentz et al, 1999), sometimes even in the presence of CNS-derived inhibitors (Cai et al, 1999).…”

Section: Abstract: Neurotrophin-3; Regeneration; Degeneration; Astromentioning

confidence: 99%

Two-Tiered Inhibition of Axon Regeneration at the Dorsal Root Entry Zone

Ramer

Duraisingam²,

Priestley

et al. 2001

J. Neurosci.

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Glial-derived inhibitory molecules and a weak cell-body response prevent sensory axon regeneration into the spinal cord after dorsal root injury. Neurotrophic factors, particularly neurotrophin-3 (NT-3), may increase the regenerative capacity of sensory neurons after dorsal rhizotomy, allowing regeneration across the dorsal root entry zone (DREZ). Intrathecal NT-3, delivered at the time of injury, promoted an upregulation of the growth-associated protein GAP-43 primarily in large-diameter sensory profiles (which did not occur after rhizotomy alone), as well as regeneration of cholera toxin B-labeled sensory axons across the DREZ and deep into the dorsal horn. However, delaying treatment for 1 week compromised regeneration: although axons still penetrated the DREZ, growth within white matter was qualitatively and quantitatively restricted. This was not associated with an impaired cell-body response (GAP-43 upregulation was equivalent for both immediate and delayed treatments), or with astrogliosis at the DREZ, which begins almost immediately after rhizotomy, but with the delayed appearance of mature ED1-expressing phagocytes in the dorsal white matter between 1 and 2 weeks after lesion, marking the beginning of myelin breakdown. After rhizotomy with immediate NT-3 treatment, regeneration continues beyond 2 weeks, but in the dorsal gray matter rather than in the degenerating dorsal columns. The ability of NT-3 to promote regeneration across the DREZ, but not after the beginning of degeneration after delayed treatment reveals a hierarchy of inhibitory influences: the astrogliotic, but not the degenerative barrier is surmountable by NT-3 treatment. Key words: neurotrophin-3; regeneration; degeneration; astrocytes; oligodendrocytes; myelin; dorsal root ganglionThe differential abilities of peripheral and central nervous tissue to support regeneration is exemplified at the dorsal root entry zone (DREZ), which marks the entry point of primary afferent axons into the spinal cord. Here, the environment changes abruptly from consisting of growth-permissive Schwann cells, to astrocytes, oligodendrocytes, and microglia, which may all inhibit regeneration (Fawcett and Asher, 1999). On contact with the DREZ, regenerating axons form club-like end bulbs or synapselike structures, (Ramon y Cajal, 1928;Carlstedt, 1985), but because of the prohibitive environment of the CNS and a paltry regenerative response of sensory neurons to rhizotomy, they never re-enter the adult cord.One strategy to encourage regeneration is to enhance the growth response of the rhizotomized neurons. GAP-43 is induced in nearly all neurons during peripheral nerve regeneration (Verge et al., 1990b), but in few neurons after rhizotomy (Schreyer and Skene, 1993), unless the root is severed very close to the DRG (Chong et al., 1996). Dorsal root axonal growth occurs at about half the rate of peripheral axons (Wujek and Lasek, 1983;Oblinger and Lasek, 1984). An experimental "conditioning" lesion to a peripheral nerve before dorsal rhizotomy doubles the rate of ...

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Differential influence of nerve growth factor on neuropeptide expression in vivo: a novel role in peptide suppression in adult sensory neurons

Cited by 370 publications

References 82 publications

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

The roles of nerve growth factor and cholecystokinin in the enhancement of morphine analgesia in a rodent model of central nervous system inflammation

Neurotrophin-3 significantly reduces sodium channel expression linked to neuropathic pain states

Two-Tiered Inhibition of Axon Regeneration at the Dorsal Root Entry Zone

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