NGF involvement in pain induced by chronic constriction injury of the rat sciatic nerve

Herzberg, Uri; Eliav, Eli; Dorsey, Jill M.; Gracely, Richard H.; Kopin, Irwin J.

doi:10.1097/00001756-199705060-00012

Cited by 139 publications

(78 citation statements)

References 10 publications

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“…However, in recent years, growing evidence supports the hypothesis that a block of NGF action could provide effective pain relief in this chronic pain condition. In the CCI model, an increase of NGF levels is observed in the cells of the injured area and in dorsal root ganglia at the level of the lesion, suggesting the involvement of NGF in the development of hyperalgesia in this model of neuropathic pain (24). Direct administration of NGF into the sciatic nerve induces hyperalgesia in rats (26), whereas NGF inhibition reduces thermal and mechanical hyperalgesia in CCI model (24,27,46), partial nerve transection (28) and partial transection of the spinal cord (47).…”

Section: Discussionmentioning

confidence: 78%

“…On one hand, NGF exerts neuroprotective and trophic action on peptidergic small-diameter dorsal root ganglia cells, reversing many of the histological changes after nerve injury (4,22), and regulates the collateral sprouting of intact nociceptive sensory axons after denervation (23). On the other hand, peripheral neuropathic pain is correlated with elevated NGF levels (24,25), and direct administration of NGF into the sciatic nerve produces hyperalgesia (26) Moreover, NGF function inhibition results in analgesia in different neuropathy-related pain protocols, such as chronic constriction injury and partial sciatic nerve transection (27,28).…”

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confidence: 99%

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The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Ugolini¹,

Marinelli

Covaceuszach

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

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Nerve growth factor (NGF) is involved in pain transduction mechanisms and plays a key role in many persistent pain states, notably those associated with inflammation. On this basis, both the NGF ligand and its receptor TrkA (tyrosine kinase A) represent an eligible target for pain therapy. Although the direct involvement of NGF in pain modulation is well established, the effect of a direct functional block of the TrkA receptor is still unknown. In this study, we have demonstrated that MNAC13, the only anti-TrkA monoclonal antibody for which function neutralizing properties have been clearly shown both in vitro and in vivo, induces analgesia in both inflammatory and neuropathic pain models, with a surprisingly long-lasting effect in the latter. The formalin-evoked pain licking responses are significantly reduced by the MNAC13 antibody in CD1 mice. Remarkably, treatment with the anti-TrkA antibody also produces a significant antiallodynic effect on neuropathic pain: repeated i.p. injections of MNAC13 induce significant functional recovery in mice subjected to sciatic nerve ligation, with effects persisting after administration. Furthermore, a clear synergistic effect is observed when MNAC13 is administered in combination with opioids, at doses that are not efficacious per se. This study represents a direct demonstration that neutralizing antibodies directed against the TrkA receptor may display potent analgesic effects in inflammatory and chronic pain.analgesia ͉ behavior ͉ mice ͉ nerve growth factor

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Ugolini¹,

Marinelli

Covaceuszach

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

View full text Add to dashboard Cite

show abstract

“…Further evidence for the involvement of peripheral nerve fibers came from Kerr et al who demonstrated the absence of NGF mediated hyperalgesia in mice lacking expression of Kv1.8 a sodium ion channel found on primary afferent neurons (Kerr et al 2001). Finally, Herzberg et al reported using the chronic constriction injury (CCI) model of neuropathic pain that the application of NGF antiserum at the site of the ligatures delayed the appearance of hyperalgesia (Herzberg et al 1997). …”

Section: Discussionmentioning

confidence: 99%

Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

Sabsovich

Wei

Guo

et al. 2008

Pain

108

126

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“…Nevertheless, the pathogenic mechanisms of the abnormal hyperexcitability of the primary sensory neurons are unclear. Concentration of nerve growth factor (NGF) in DRG was reported to increase after the artificial nerve injury (9), and injection of exogenous NGF into healthy rats induced hyperalgesia (16). These reports suggest that NGF correlates with the pathogenesis of neuropathic pain.…”

mentioning

confidence: 99%

Nerve growth factor-induced hyperexcitability of rat sensory neuron in culture

et al. 2005

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Abnormal spontaneous firing of primary sensory neurons is considered to be a cause of neuropathic pain. However, pathogenic mechanisms of hyperexcitable sensory neurons in neuropathic model animals are unclear. We examined effects of chronic treatment of nerve growth factor (NGF), one of candidate mediators for the pathogenesis, on excitability of sensory neurons by voltage-clamped recording in a cell-attached configuration. From rat dorsal root ganglion (DRG) neurons cultured without NGF, only stable holding currents without spontaneous firing activity were recorded. On the other hand, more than 20% neurons cultured in the presence of NGF for more than 3 days showed spontaneous current spikes at frequencies between 0.1 and 5 Hz. Each spikes had an initial inward phase followed by the outward phase, resulted from spontaneous transient depolarization followed by transient hyperpolarization. These spontaneous spikes were abolished by tetrodotoxin, lidocaine and reduction of extracellular concentration of Na + from 154 mM to 100 mM, in all-or-none fashion, suggesting that spontaneous current spikes reflected spontaneous action potentials. From these results, it became evident that DRG neurons of adult rats had a nature to respond to NGF and obtained the abnormal hyperexcitability to fire spontaneously.Peripheral nerve injury frequently results in severe chronic pain, neuropathic pain that is poorly responsive to general analgesic therapy, and remains as an unsolved problem in health. Experimental injury of the peripheral nerve in experimental animals induces hyperalgesia and allodynia (2,5,13,22,31,32). Although primary sensory neurons of healthy animals are "silent" in electrophysiology without excitatory inputs from other neurons or sensational inputs, abnormal spontaneous firing was observed in sensory neurons of animals with nerve injury (6,11,12,18). Such abnormal firing is considered to be a cause of neuropathic pain. Such spontaneous firing was observed at the local injured site and also at the soma of the dorsal root ganglion (DRG) neurons (30). Subthreshold membrane potential oscillation and the spontaneously generated action potentials were recorded in DRG neurons freshly isolated from nerveinjured rats by the intracellular microelectrode method (1,17,26) and the whole-cell patch clamp method in the current clamp mode (20,27). Nevertheless, the pathogenic mechanisms of the abnormal hyperexcitability of the primary sensory neurons are unclear. Concentration of nerve growth factor (NGF) in DRG was reported to increase after the artificial nerve injury (9), and injection of exogenous NGF into healthy rats induced hyperalgesia (16). These reports suggest that NGF correlates with the pathogenesis of neuropathic pain. Small DRG neurons, which respond to noxious sensation, express TrkA

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NGF involvement in pain induced by chronic constriction injury of the rat sciatic nerve

Cited by 139 publications

References 10 publications

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

Nerve growth factor-induced hyperexcitability of rat sensory neuron in culture

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