Progress in neurobiology
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Progress in neurobiology · Jun 2000
ReviewWind-up of spinal cord neurones and pain sensation: much ado about something?
Wind-up is a frequency-dependent increase in the excitability of spinal cord neurones, evoked by electrical stimulation of afferent C-fibres. Although it has been studied over the past thirty years, there are still uncertainties about its physiological meaning. Glutamate (NMDA) and tachykinin NK1 receptors are required to generate wind-up and therefore a positive modulation between these two receptor types has been suggested by some authors. ⋯ On the other hand, wind-up, central sensitisation and hyperalgesia are not the same phenomena, although they may share common properties. Wind-up can be an important tool to study the processing of nociceptive information in the spinal cord, and the central effects of drugs that modulate the nociceptive system. This paper reviews the physiological and pharmacological data on wind-up of spinal cord neurones, and the perceptual correlates of wind-up in human subjects, in the context of its possible relation to the triggering of hyperalgesic states, and also the multiple factors which contribute to the generation of wind-up.
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Near-infrared (IR) light easily penetrates biological tissue, and the information offered by in vivo spectroscopy of cerebral oxygenation is detailed and comes with a high temporal resolution. Near-IR light spectroscopy (NIRS) reflects cerebral oxygenation during arterial hypotension, hypoxic hypoxaemia and hypo- and hypercapnia. As determined by dual-wavelength NIRS, the cerebral O2 saturation integrates the arterial O2 content and the cerebral perfusion, and as established for skeletal muscle, NIRS obtains information on tissue oxygenation and metabolism beyond that obtained by venous blood sampling. ⋯ By NIRS, reduction of cytochrome oxidase is demonstrated during hypoxic hypoxaemia and head-up tilt-induced arterial hypotension, but the changes are small. In the clinical setting, NIRS offers useful information in patients with both systemic and local cerebral circulatory impairment, for example, during cranial trauma, surgery on the cerebral arteries, orthostasis and acute heart failure. Whereas mapping of the brain circulation is needed for jugular venous sampling to reflect either global or local oxygenation, the determination of cerebral oxygenation by NIRS has the advantage of localized monitoring of the cerebral cortex.
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Progress in neurobiology · Apr 1999
ReviewNociceptin/orphanin FQ: role in nociceptive information processing.
Recently, opioid receptor like1 (ORL1) receptor was identified. The ORL1 receptor is a G protein coupled receptor and the sequence of the ORL1 receptor is closely related to that of the opioid receptors. Nociceptin/orphanin FQ has been identified as a potent endogenous agonist of the ORL1 receptor and the sequence of nociceptin/orphanin FQ is closely related to that of dynorphin A. ⋯ Intracerebroventricular (i.c.v.) injection of nociceptin/orphanin FQ produced hyperalgesia and allodynia and antagonized morphine analgesia. On the other hand, intrathecal injection of low dose nociceptin/orphanin FQ produces allodynia, but high dose of nociceptin/orphanin FQ produces an analgesic effect. Although we do not fully understand the mechanisms that produce the difference between the effect of i.c.v. injection of nociceptin/orphanin FQ and that of intrathecal injection of nociceptin/orphanin FQ, we believe that spinal ORL1 receptor may be the next receptor which should be targeted by drugs designed for the treatment of pain.
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Progress in neurobiology · Feb 1999
ReviewActivity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system.
This review primarily discusses work that has been performed in our laboratories and that of our direct collaborators and therefore does not represent an exhaustive review of the current literature. Our aim is to further discuss the role that gene expression plays in neuronal plasticity and pathology. In the first part of this review we examine activity-dependent changes in the expression of inducible transcription factors (ITFs) and neurotrophins with long-term potentiation (LTP) and kindling. ⋯ We also discuss whether loss of retrograde transport of neurotrophic factors such as nerve growth factor following nerve transection triggers the selective and prolonged expression of c-Jun in axotomized neurons and whether c-Jun is responsible for regeneration or degeneration of these axotomized neurons. In the last section we further examine the role that gene expression may play in memory formation, epileptogenesis and neuronal degeneration, lastly speculating whether the expression of various growth factors after brain injury represents an endogenous neuroprotective response of the brain to injury. Here we discuss our results which show that pharmacological enhancement of this response with exogenous application of IGF-1 or TGF-beta reduces neuronal loss after brain injury.
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The highly disagreeable sensation of pain results from an extraordinarily complex and interactive series of mechanisms integrated at all levels of the neuroaxis, from the periphery, via the dorsal horn to higher cerebral structures. Pain is usually elicited by the activation of specific nociceptors ('nociceptive pain'). However, it may also result from injury to sensory fibres, or from damage to the CNS itself ('neuropathic pain'). ⋯ This neuronal framework is then exploited for a consideration of peripheral, spinal and supraspinal mechanisms involved in the induction of pain by stimulation of peripheral nociceptors, by peripheral nerve injury and by damage to the CNS itself. Finally, a hypothesis is forwarded that neurotrophins may play an important role in central, adaptive mechanisms modulating nociception. An improved understanding of the origins of pain should facilitate the development of novel strategies for its more effective treatment.