The European journal of neuroscience
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Comparative Study
Anti-nociception induced by systemic or PAG-microinjected lysine-acetylsalicylate in rats. Effects on tail-flick related activity of medullary off- and on-cells.
Previous experiments using metamizol have shown that this non-steroidal anti-inflammatory drug (NSAID) produces a central anti-nociceptive effect probably through neural substrates that also support the analgesic effects of opiates, such as the periaqueductal grey matter (PAG) and the off- and on-cells of the rostral ventromedial medulla (RVM). Off- and on-cells have been postulated to respectively inhibit and facilitate nociceptive transmission, since the heat-elicited tail flick reflex (TF) occurs only after off-cells have decreased (pause), and on-cells, have increased (burst) their activity. The aim of the present study was to examine whether the effect of metamizol upon TF and off- and on-cells responses could be generalized to other NSAIDs such as, in this case, lysine-acetylsalicylate (LASA). ⋯ Neuronal responses and TF retained their mutual time relationship but shifted simultaneously toward longer latencies. This anti-nociceptive effect of LASA was dose-dependent, present 5 min after administration and reached a maximum in 30 min for both administration methods. These data confirm that analgesics typically defined as peripherally-acting, such as metamizol and LASA in this study, may also have an anti-nociceptive effect by acting directly upon PAG, and suggest that this central effect involves the RVM off- and on-cells.
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Comparative Study
CO2 stimulation of the cornea: a comparison between human sensation and nerve activity in polymodal nociceptive afferents of the cat.
Excitation of nociceptors by low pH has been proposed as a cause of pain following tissue injury. Here we have studied the effect of pH reductions caused by application of CO2 pulses to the cornea on the activity of corneal afferent nerves of the cat and on the magnitude of pain sensations in humans. Single-unit activity was recorded from corneal afferent fibres in anaesthetized cats. ⋯ Curves of CO2 concentration versus neural discharges in the cat and versus psychophysical sensation in humans were very similar. These results show that corneal polymodal nociceptors respond to protons, and encode changes in CO2 concentration presumably reflecting pH changes. The same stimulus evokes corneal pain sensations in humans, thus opening the possibility of using CO2 as an effective stimulus for corneal aesthesiometry.
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Using monoiodinated peptide YY (PYY) and galanin as radioligands, and neuropeptide Y (NPY) fragments, the distribution of NPY binding sites and its subtypes Y1 and Y2, and of galanin binding sites, was investigated in rat and monkey lumbar (L) 4 and L5 dorsal root ganglia (DRG) and spinal cord before and after a unilateral sciatic nerve cut, ligation or crush. Receptor autoradiography revealed that [125I]PYY bound to some DRG neurons and a few nerve fibres in normal rat DRG, and most of these neurons were small. NPY binding sites were observed in laminae I-IV and X of the rat dorsal horn and in the lateral spinal nucleus, with the highest density in laminae I-II. [125I]PYY binding was most strongly attenuated by NPY13-36, a Y2 agonist, and partially inhibited by [Leu31,Pro34]NPY, a Y1 agonist, in both rat DRG and the dorsal horn of the spinal cord. ⋯ Axotomy had no effect on galanin binding in rat DRG and dorsal horn. However, galanin receptor binding was observed in many neurons in monkey L4 and L5 DRG and in laminae I-IV and X of monkey L4 and L5 spinal cord, with the highest intensity in laminae I-II. No marked effect of axotomy was observed on the distribution and intensity of galanin binding in monkey DRG or spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)
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This study investigated the pattern of axonal projections of single corticothalamic neurons from the cortical barrel field representing the vibrissae in the rat. Microiontophoretic injections of biocytin were performed in cortical layers V and VI to label small pools of corticothalamic cells and their intrathalamic axonal projections. After a survival period of 48 h, the animals were perfused and the tissue was processed for biocytin histochemistry. ⋯ All corticothalamic axons derived from layer VI cells, but not those derived from layer V cells, gave off collaterals as they traversed the thalamic reticular complex. These observations are discussed in the light of previous studies bearing on the topological organization and function of corticothalamic projections to VPm and Pom in rats. The possibility that a similar cellular specificity and a similar organizational plan may characterize corticothalamic relationships in other sensory systems is also considered.
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Mechanisms underlying the hyperalgesia induced by a single systemic injection of nerve growth factor (NGF) in adult rats were studied in vivo. A single dose of NGF initiated a prolonged thermal hyperalgesia to a radiant heat source within minutes that lasted for days. Animals which had been pretreated with the mast cell degranulating compound 48/80 or either one of two specific 5-hydroxytryptamine receptor antagonists (ICS 205-930 and methiothepin) also developed an NGF-induced thermal hyperalgesia, but onset was delayed by more than 3 h. ⋯ These data indicate that NGF-induced thermal and mechanical hyperalgesia are mediated by different mechanisms. The rapid onset component of thermal hyperalgesia is due to a peripheral mechanism involving the degranulation of mast cells, whereas the late component involves central NMDA receptors. In contrast, the NGF-induced mechanical hyperalgesia seems to be independent of mast cell degranulation or central NMDA receptor sites.