Activity-dependent neuronal plasticity following tissue injury and inflammation
TL;DR: A model has been proposed in which dynorphin, substance P and calcitonin gene-related peptide enhance excitability at NMDA receptor sites, leading first to dorsal horn hyperexcitability and then to excessive depolarization and excitotoxicity.
About: This article is published in Trends in Neurosciences.The article was published on 1992-01-01. It has received 936 citations till now. The article focuses on the topics: Dynorphin & Hyperalgesia.
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TL;DR: The present review focuses on the organisation of descending pathways and their pathophysiological significance, the role of individual transmitters and specific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls.
2,565 citations
Cites background from "Activity-dependent neuronal plastic..."
..., 2001c) which are associated with an upregulation of DYN gene expression in the DH (Millan, 1986, 1990, 1993; Dubner and Ruda, 1992; Bian et al., 1999; Malan et al., 2000)....
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TL;DR: This review examines the clinical and experimental evidence which points to a contribution of central Neurol plasticity to the development of pathological pain, and assesses the physiological, biochemical, cellular and molecular mechanisms that underlie plasticity induced in the central nervous system in response to noxious peripheral stimulation.
Abstract: Peripheral tissue damage or nerve injury often leads to pathological pain processes, such as spontaneous pain, hyperalgesia and allodynia, that persist for years or decades after all possible tissue healing has occurred. Although peripheral neural mechanisms, such as nociceptor sensitization and neuroma formation, contribute to these pathological pain processes, recent evidence indicates that changes in central neural function may also play a significant role. In this review, we examine the clinical and experimental evidence which points to a contribution of central neural plasticity to the development of pathological pain. We also assess the physiological, biochemical, cellular and molecular mechanisms that underlie plasticity induced in the central nervous system (CNS) in response to noxious peripheral stimulation. Finally, we examine theories which have been proposed to explain how injury or noxious stimulation lead to alterations in CNS function which influence subsequent pain experience.
1,974 citations
Cites background from "Activity-dependent neuronal plastic..."
...The high percentage of preprodynorphin and preproenkephalin mRNA colocalized with Fos-IR has been taken as evidence that Fos phosphoprotein signalling is coupled to dynorphin and enkephalin gene transcription (Dubner and Ruda 1992)....
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...Dubner and Ruda (1992) suggest that c-fos-induced increases in dynorphin gene expression and dynorphin peptide levels lead to enhanced excitability and the development of expanded receptive fields....
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...MK-801 also reduces the adjuvant inflammation-induced expansion of the receptive fields of nociceptive neurons in spinal cord dorsal horn (Dubner and Ruda 1992)....
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TL;DR: A global account of mechanisms involved in the induction of pain is provided, including neuronal pathways for the transmission of nociceptive information from peripheral nerve terminals to the dorsal horn, and therefrom to higher centres.
1,752 citations
Cites background from "Activity-dependent neuronal plastic..."
...Although certain classes of ININ may attenuate the activity of EXINs, little direct information is available in this regard (Dubner and Ruda, 1992)....
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...Further, DH levels of ININ-localized enkephalins are also increased under conditions of PAF in ̄ammation (Dubner and Ruda, 1992; Millan, 1993; Ossipov et al., 1997) and there is additional evidence that phenotype changes in DH-localized ININs may counter nociception....
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TL;DR: This article reviews findings up to the end of 1997 about the inducible transcription factors c-Jun, JunB, JunD, c-Fos, FosB, Fra,1, Fra-2, Krox-20 (Egr-2) and Krox -24 (NGFI-A, Egr-1, Zif268) as they pertain to gene expression in the mammalian nervous system and describes their expression and possible roles in glial cells.
1,361 citations
TL;DR: Analysis of the molecular mechanisms underlying the generation and maintenance of central sensitization and LTP indicates that, although there are differences between the synaptic plasticity contributing to memory and pain, there are also striking similarities.
1,361 citations
References
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TL;DR: Both the thermal method and the Randall‐Selitto mechanical method detected dose‐related hyperalgesia and its blockade by either morphine or indomethacin, but the Thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.
Abstract: A method to measure cutaneous hyperalgesia to thermal stimulation in unrestrained animals is described. The testing paradigm uses an automated detection of the behavioral end-point; repeated testing does not contribute to the development of the observed hyperalgesia. Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws and these latency changes corresponded to a decreased thermal nociceptive threshold. Both the thermal method and the Randall-Selitto mechanical method detected dose-related hyperalgesia and its blockade by either morphine or indomethacin. However, the thermal method showed greater bioassay sensitivity and allowed for the measurement of other behavioral parameters in addition to the nociceptive threshold.
4,829 citations
Journal Article•
4,241 citations
TL;DR: Physiological stimulation of rat primary sensory neurons causes the expression of c-fos-protein-like immunoreactivity in nuclei of postsynaptic neurons of the dorsal horn of the spinal cord, suggesting that synaptic transmission may induce rapid changes in gene expression in certain post Synaptic neurons.
Abstract: It has been suggested that the proto-oncogenes c-fos and c-myc participate in the control of genetic events which lead to the establishment of prolonged functional changes in neurons. Expression of c-fos and c-myc are among the earliest genetic events induced in cultured fibroblast and phaeochromocytoma cell lines by various stimuli including growth factors, peptides and the intracellular second messengers diacylglycerol, cAMP and Ca2+. We report here that physiological stimulation of rat primary sensory neurons causes the expression of c-fos-protein-like immunoreactivity in nuclei of postsynaptic neurons of the dorsal horn of the spinal cord. Activation of small-diameter cutaneous sensory afferents by noxious heat or chemical stimuli results in the rapid appearance of c-fos-protein-like immunoreactivity in the superficial layers of the dorsal horn. However, activation of low-threshold cutaneous afferents results in fewer labelled cells with a different laminar distribution. No c-fos induction was seen in the dorsal root ganglia, gracile nucleus or ventral horn. Thus, synaptic transmission may induce rapid changes in gene expression in certain postsynaptic neurons.
1,970 citations
TL;DR: Results indicate that NMDA receptors are involved in the induction and maintenance of the central sensitization produced by high threshold primary afferent inputs and have a bearing both on the potential role of NMDA antagonists for pre‐emptive analgesia and for treating established pain states.
Abstract: Repetitive stimulation of small diameter primary afferent fibres produces a progressive increase in action potential discharge (windup) and a prolonged increase in the excitability of neurones in the spinal cord following the stimulus. Previous studies have demonstrated that windup is the consequence of the temporal summation of slow synaptic potentials and that the slow potentials and windup are reduced by pretreatment with N-methyl-D-aspartic acid (NMDA) antagonists. We have now examined whether primary afferent induced hypersensitivity states in flexor motoneurones are also dependent on the activation of NMDA receptors and whether windup is a possible trigger for the production of the central hypersensitivity. Both a non-competitive (MK-801) and a competitive (D-CPP) NMDA antagonist, at doses that did not modify the baseline reflex, reduced the facilitation of the flexor reflex produced by either brief electrical stimulation of the sural nerve (1 Hz for 20 sec at C-fibre strength), or by the cutaneous application of the chemical irritant mustard oil. These antagonists also prevented windup from occurring in the motoneurones. When the the MK-801 and the D-CPP were administered once a state of central facilitation had been induced by prior treatment with mustard oil, they returned the facilitated reflex to its pretreatment level. These results indicate that NMDA receptors are involved in the induction and maintenance of the central sensitization produced by high threshold primary afferent inputs. Because central sensitization is likely to contribute to the post-injury pain hypersensitivity states in man, these data have a bearing both on the potential role of NMDA antagonists for pre-emptive analgesia and for treating established pain states.
1,903 citations
TL;DR: The practice and theoretical basis of pain measurement is reviewed and critically examined in the areas of animal research, human subjects laboratory investigation and clinical study, and subjective report procedures are evaluated in human laboratory and clinical areas.
Abstract: The practice and theoretical basis of pain measurement is reviewed and critically examined in the areas of animal research, human subjects laboratory investigation and clinical study. The advantages and limitations of both physiological and behavioral methods are discussed in each area, and subjective report procedures are evaluated in human laboratory and clinical areas. The need for procedures that bridge these areas is emphasized and specific issues are identified. Progress in the technology of pain measurement over recent decades is reviewed and directions for future work are suggested.
1,057 citations