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Chronic Pain States (chronic + pain_states)
Selected AbstractsTranslating nociceptor sensitivity: the role of axonal protein synthesis in nociceptor physiologyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2009Theodore J. Price Abstract The increased sensitivity of peripheral pain-sensing neurons, or nociceptors, is a major cause of the sensation of pain that follows injury. This plasticity is thought to contribute to the maintenance of chronic pain states. Although we have a broad knowledge of the factors that stimulate changes in nociceptor sensitivity, the cellular mechanisms that underlie this plasticity are still poorly understood; however, they are likely to involve changes in gene expression required for the phenotypic and functional changes seen in nociceptive neurons after injury. While the regulation of gene expression at the transcriptional level has been studied extensively, the regulation of protein synthesis, which is also a tightly controlled process, has only recently received more attention. Despite the established role of protein synthesis in the plasticity of neuronal cell bodies and dendrites, little attention has been paid to the role of translation control in mature undamaged axons. In this regard, several recent studies have demonstrated that the control of protein synthesis within the axonal compartment is crucial for the normal function and regulation of sensitivity of nociceptors. Pathways and proteins regulating this process, such as the mammalian target of rapamycin signaling cascade and the fragile X mental retardation protein, have recently been identified. We review here recent evidence for the regulation of protein synthesis within a nociceptor's axonal compartment and its contribution to this neuron's plasticity. We believe that an increased understanding of this process will lead to the identification of novel targets for the treatment of chronic pain. [source] The medullary dorsal reticular nucleus enhances the responsiveness of spinal nociceptive neurons to peripheral stimulation in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Christophe Dugast Abstract Single-unit spinal recordings combined with application of glutamate into the medullary dorsal reticular nucleus were used to assess the action of this nucleus upon deep dorsal horn neurons in rats. Injection of high glutamate concentrations (10 and 100 mm) induced a dramatic and long-lasting increase of the responses of wide-dynamic range neurons to electrical stimulation of the sciatic nerve in the noxious range, without affecting ongoing discharges. Post-stimulus time histograms revealed that this increase concerned the post-discharge, but not A- or C-fibre-mediated responses, which remained unchanged independently of the stimulation frequency applied. The onset of the glutamate-induced response enhancement occurred with a concentration-dependent time delay and developed slowly until its maximum. These data indicate that the medullary dorsal reticular nucleus exerts a facilitating action upon deep dorsal horn wide-dynamic range neurons by enhancing their capacity to respond to peripheral stimulation through prolongation of their discharge. This action is accompanied by the strengthening of wind-up of deep dorsal horn wide-dynamic range neurons, hence providing a plausible substrate for chronic pain states. These results are in agreement with previous behavioural studies suggesting a pronociceptive role for the dorsal reticular nucleus [Almeida et al. (1996) Brain Res. Bull., 39, 7,15; Almeida et al. (1999) Eur. J. Neurosci., 11, 110,122], and support the involvement of a reverberating circuit, previously described in morphological studies [Almeida et al. (1993) Neuroscience, 55, 1093,1106; Almeida et al. (2000) Eur. J. Pain, 4, 373,387], which probably operates only at a certain threshold of activation. [source] Is There Hope for Chronic Pain and Headache?HEADACHE, Issue 8 2007Marcela Romero-Reyes DDS Currently the clinical needs for pain and headache management are not met. Despite the numerous and exciting recent advances in understanding the molecular and cellular mechanisms that originate pain, we cannot yet fully explain the mechanism underlying the biology of chronic pain. Pain is a natural mechanism preserving our species survival; however, when the protective quality is lost, physiologic changes to the peripheral and central nervous systems result in the formation of chronic pain states. Once we understand how this chronic pain state is created, either through genetic, environmental, therapeutic, or other triggers we may be able to enhance our species existence, limiting maladaptive pain and suffering. The future therapeutic targets will need to address the genetics, neurophysiologic changes of the neurons and brain as well as help control immune systems including the glia. The key to successful headache and pain therapy is research aimed at prevention and minimizing the plastic changes triggering chronic pain. [source] The behavioral importance of dynamically activated descending inhibition from the nucleus reticularis gigantocellularis pars alpha. (University Hospital of Wales, Cardiff, United Kingdom) Pain 2001;92:53,62.PAIN PRACTICE, Issue 4 2001J. Azami This study demonstrates the effects of nucleus reticularis gigantocellularis pars alpha (GiA) on the behavioral response during application of standardized noxious stimuli. As this system is activated in response to noxious stimulation, it is possible that chronic pain states may also activate GiA. Therefore, this study investigated this possibility in animals following partial sciatic nerve ligation (an animal model of chronic pain). Male Wistar rats (280,310 g) were anesthetized with halothane (0.5% to 2% in O2). Guide cannulae for microinjections were stereotaxically placed above GiA. In one group of animals the sciatic nerve was partially litigated. Animals were allowed to recover for 4,6 days. The responses of each animal during the formalin test and the tail flick test were recorded on different days. Microinjections (0.5 ,l) of either ,-aminobutyric acid (GABA, 200 mM), D-L homocysteic acid (DLH, 25 mM), or 0.9% saline (as control) into GiA were preformed during these tests in a randomized, blind manner. In animals without sciatic nerve ligation, microinjection of GABA to GiA did not significantly affect the animal's response during the tail flick test. However, microinjection of DLH significantly increased the latency of tail flick from 6.2 ± 0.8 to 8.4 ± 0.5 seconds for up to 15 minutes. Microinjection of GABA to GiA increased the behavioral response to formalin between 10 and 20 minutes postinjection, while microinjection of DLH reduced this response at all time points except 10 minutes postinjection (n = 8, p < 0.05, Mann-Whitney U -test). In animals with sciatic nerve ligation, microinjections (0.5 ,l) of either GABA (200 mM), or saline (as control) into GiA contralateral to the partial sciatic ligation were performed during these tests in a randomized, blind manner. Partial sciatic ligation significantly reduced the behavioral response to contralaterally applied formalin from 15 minutes postinjection onwards, compared to controls without sciatic nerve ligation. Microinjection of GABA GiA significantly increased the behavioral response to formalin from 20 to 50 minutes postinjection. The inactivation of GiA only causes behavioral effects in nociceptive tests of a long enough duration to activate the system (ie, the formalin test but not the tail flick test). Chemical activation of the system affects both tests. Conclude that these data strongly support the concept of an important analgesic system that is activated in response to noxious stimulation, and subsequently acts to reduce behavioral responses to noxious stimuli. Comment by Leland Lou, M.D. This is a rat study that looked at the presence of inhibitory spinal multireceptive cells modifying and decreasing the behavioural response to noxious stimuli. While no direction was given as to the source of noxious stimuli inhibition in chronic pain, great effort was made to report a possible differential response of the C-fiber pain system versus the large sensory fibers. After review it seems that the authors believed that the nucleus reticularis gigantocellularis pars alpha maybe a central processor of the inhibitory response. It is still too early to assess the clinical impact of this study. [source] | ||||||||||