Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain.

By R. Ji, Clifford J. Woolf. Neurobiology of Disease, 2001

748 citations recorded by the source corpus.

Pathological pain, consisting of tissue injury-induced inflammatory and nerve injury-induced neuropathic pain, is an expression of neuronal plasticity. One component of this is that the afferent input generated by injury and intense noxious stimuli triggers an increased excitability of nociceptive neurons in the spinal cord. This central sensitization is an activity-dependent functional plasticity that results from activation of different intracellular kinase cascades leading to the phosphorylation of key membrane receptors and channels, increasing synaptic efficacy. Central sensitization is both induced and maintained in a transcription-independent manner. Several different intracellular signal transduction cascades converge on MAPK (mitogen-activated protein kinase), activation of which appears to be a master switch or gate for the regulation of central sensitization. In addition to posttranslational regulation, the MAPK pathway may also regulate long-term pain hypersensitivity, via transcriptional regulation of key gene products. Pharmacological intervention targeted specifically at the signal transduction pathways in nociceptive neurons may provide, therefore, new therapeutic opportunities for pathological pain.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/5be72c053eaf6c6a343549756a3a609cef06be19

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Clifford J. Woolf
2. R. Ji
3. Z. Zhuang
4. M. Suter
5. P. Gerner
6. R. Meyer
7. J. Campbell
8. Shan-xue Jin

In Molecular Biology

1. Clifford J. Woolf
2. R. Ji
3. M. Suter
4. R. Meyer
5. J. Campbell
6. Z. Zhuang
7. P. Gerner
8. M. Malcangio

In Physiology

1. Clifford J. Woolf
2. R. Ji
3. M. Suter
4. Z. Zhuang
5. P. Gerner
6. M. Malcangio
7. R. Gereau
8. G. Strichartz

Citations in the corpus

• p38 Mitogen-Activated Protein Kinase Is Activated after a Spinal Nerve Ligation in Spinal Cord Microglia and Dorsal Root Ganglion Neurons and Contributes to the Generation of Neuropathic Pain (2003, background): “ERK is involved both in cell proliferation and differentiation during development and in neuronal plasticity in the adult. p38 and JNK are stress-activated protein kinases and participate in injury responses and cell death (Widmann et al., 1999; Ji and Woolf, 2001).”
• Central sensitization and LTP: do pain and memory share similar mechanisms? (2003, background): “moting trafficking of receptors to the synaptic membrane [7, 42 ].”
• MAP kinase and pain (2008, background): “…plasticity in the adult (Impey et al., 1999). p38 and JNK are activated by proinflammatory cytokines and cellular stress and play essential roles in regulating inflammatory responses, neurodegeneration, and cell death (Widmann et al., 1999; Ji and Woolf, 2001; Kumar et al., 2003; Gao and Ji, 2008).”
• Mechanisms of neuropathic pain. (2006, background): “These findings produce a dilemma because activity in C fibers is thought to be necessary to evoke the central sensitization mechanisms that account for the hyperalgesia (Ji and Woolf, 2001).”
• p38 MAPK, microglial signaling, and neuropathic pain (2007, background): “In addition, p38 also induces release of PGE2 and IL1β via rapid posttranslational regulation (step-14).”
• ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model (2005, background): “ERK activation in dorsal horn neurons contributes both to the induction and maintenance of acute central sensitization (Ji and Woolf, 2001; Ji et al., 1999, 2002a, 2003; Kawasaki et al., 2004; Woolf, 1983; Woolf and Salter, 2001).”