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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pain arising from deep structures (muscles, joints, viscera) is the type of pain of most clinical relevance and also the type of pain about whose central representation we have the least knowledge. In contrast to cutaneous pain which evokes defensive behaviours, hypertension and tachycardia, the physiological reactions to most deep pain (especially if persistent) usually include quiescence, hypotension, bradycardia and decreased reactivity to the environment. Excitation of neurons within a discrete ventrolateral midbrain periaqueductal gray region evokes a reaction seemingly identical to that evoked by pain arising from deep structures. We report here, using the technique of the noxious stimulus-evoked expression of the immediate-early gene, c-fos, that neurons within this same ventrolateral periaqueductal gray region are selectively activated by a range of deep somatic and visceral nociceptive manipulations. Thus we have identified a specific brain region that both receives convergent, deep somatic and visceral nociceptive input, and which mediates the behavioural and physiological reactions characteristic of most deep pain.
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PMID:Convergence of deep somatic and visceral nociceptive information onto a discrete ventrolateral midbrain periaqueductal gray region. 783 71

The influence of stimulus duration on spinal induction of the c-fos proto-oncogene was analysed in the rat by pinching or heating the skin for periods varying from 20 s to 2 h. At stimulation periods shorter than 20 min, c-fos activation occurred in laminae I-IIi following mechanical stimulation and I-IIo following thermal stimulation. Mechanical stimulation produced delayed activation in laminae III-IV, V and VII at 30 min, 60 min and 2 h, respectively, and thermal stimulation in lamina IIi at 50 min. It is suggested that late c-fos activation signals inflammatory pain and is due to sensitization of primary afferent neurones.
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PMID:Spinal c-fos expression is differentially induced by brief or persistent noxious stimulation. 784 61

Increased pain sensitivity (hyperalgesia) and persistent nociception following peripheral tissue injury depends both on an increase in the sensitivity of primary afferent nociceptors at the site of injury (peripheral sensitization), and on an increase in the excitability of neurons in the central nervous system (central sensitization). We will review evidence that central sensitization, and the persistent nociception it leads to, are dependent on an action of glutamate and aspartate at excitatory amino acid (EAA) receptors. Additional evidence will be presented implicating a role of various intracellular second messengers that are coupled to EAA receptors (nitric oxide, arachidonic acid, and protein kinase C) to central sensitization and persistent nociception following tissue injury. Finally, we will examine the evidence for a contribution of molecular events, including noxious stimulus-induced expression of immediate-early genes such as c-fos to persistent nociception.
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PMID:The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats. 791 27

In previous studies we reported that although morphine dose dependently inhibits noxious stimulus-evoked expression of the c-fos proto-oncogene in the rat spinal cord, morphine was without effect in certain populations of presumed nociresponsive neurons, even under conditions of complete behavioral analgesia. To determine whether the neurons that continue to express the c-fos gene include projection neurons, we evaluated the effect of morphine on noxious stimulus-evoked c-fos expression in spinoparabrachial neurons retrogradely labeled with Fluoro-gold. In the formalin test, we found that morphine analgesia was associated with a significant reduction in the number of Fos-like-immunoreactive spinoparabrachial projection neurons in the lateral reticulated area of the neck of the dorsal horn. Morphine, however, did not reduce the number of Fos-like-immunoreactive spinoparabrachial projection neurons either in the superficial dorsal horn or in the area around the central canal. These results indicate that under conditions of morphine analgesia two distinct populations of spinoparabrachial neurons can be recognized on the basis of their expression of the c-fos gene in response to noxious stimulation. Since the expression of the c-fos gene has been correlated with neuronal activity, these data suggest that activity, and central transmission of nociceptive information, persists in certain nociresponsive projection neurons during morphine analgesia. Alternatively, if activity has, in fact, been blocked in these neurons, our results indicate that injury can produce significant molecular changes in neurons even though the neuronal activity and pain associated with the injury is blocked by morphine.
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PMID:Differential effects of morphine on noxious stimulus-evoked fos-like immunoreactivity in subpopulations of spinoparabrachial neurons. 799 73

Behavioral and electrophysiological studies have shown that a noxious stimulus applied to one part of the body can reduce the response to a subsequent noxious stimulus elsewhere on the body. This phenomenon is referred to as diffuse noxious inhibitory controls (DNIC). In the present study we used immunocytochemical labeling for the Fos protein product of the c-fos proto-oncogene to determine the location of lumbar spinal nociresponsive neurons that are inhibited by a spatially remote noxious stimulus. Repetitive hindpaw pinch evoked pronounced Fos-like immunoreactivity in the superficial and deep laminae of the lumbar spinal cord. Placing the tail in 50 degrees C water before each hindpaw pinch significantly reduced Fos-like immunoreactivity in these regions. These data demonstrate that nociresponsive neurons in both the superficial and deep laminae of the spinal cord are sensitive to inhibition by a spatially remote noxious conditioning stimulus.
Pain 1994 Mar
PMID:Diffuse noxious inhibitory controls reduce the expression of noxious stimulus-evoked Fos-like immunoreactivity in the superficial and deep laminae of the rat spinal cord. 802 27

We have previously shown that during the development of adjuvant-induced arthritis (AIA), and without any peripheral stimulation, the number of Fos-like immunoreactive (Fos-LI) neurons in lumbar spinal cord increases in parallel with the clinical and behavioral signs of the disease and peaks 3 weeks after the inoculation which corresponds to the maximal stage of hyperalgesia (Abbadie and Besson 1992a). The aim of this study was to evaluate the suitability of the Fos-LI technique to gauge the effects of the two most prescribed analgesics, aspirin and acetaminophen (paracetamol), on spinal cord neurons of polyarthritic rats. The effects of the two drugs were tested on the "evoked" Fos-LI induced by peripheral mechanical noxious stimulus, as well as the effects of a chronic treatment on "basal" Fos-LI appearing during the development of polyarthritis in the absence of any intentional stimulation. We showed that: (1) Fos-LI evoked by ankle stimulation was not modified by either aspirin (150 mg/kg i.v.) or pro-acetaminophen (300 mg/kg i.v.) injection or by a 10-day chronic treatment with acetaminophen (250 or 500 mg/kg/day). (2) Despite the fact that the clinical signs of arthritis were reduced, basal Fos-LI induced by AIA disease was not changed after a 2-week chronic treatment with either aspirin (300 mg/kg/day) or acetaminophen (500 mg/kg/day) starting 3 weeks after AIA inoculation, i.e., at the maximal stage of hyperalgesia and when Fos-LI is maximal. This observation questions the suitability of Fos-LI technique to gauge the effects of mild analgesics. (3) In contrast, when the same chronic treatment was applied during the development of AIA, i.e., 1 week after inoculation, the number of Fos-LI nuclei was significantly decreased (about 50%) in aspirin- and acetaminophen-treated groups as compared to vehicle-treated groups. In parallel, the clinical signs of AIA disease were blocked by the two drug treatments. In addition, 2 weeks after the end of treatment, neither the clinical signs nor the number of Fos-LI increased again. The fact that the two drugs are able to prevent c-fos expression during development of arthritis, but not to interfere with already existing c-fos expression, suggests that for pharmacological investigations this technique should be used with caution. Thus, the potential use of Fos-LI to gauge the effects of non-steroidal antinociceptive drugs and other mild analgesics during chronic disease such as arthritis is discussed.
Pain 1994 Apr
PMID:Chronic treatments with aspirin or acetaminophen reduce both the development of polyarthritis and Fos-like immunoreactivity in rat lumbar spinal cord. 778 10

In this experiment, three groups were used to detect c-fos expression in the CNS in the awake male, S.D. rats, i.e, EA of "Quanliao" (14 Hz), electrostimulation of the rat tail (0.4-0.6 mA) and the control. Fos was identified by ABC immunohistochemical method. The results were as follows: I. The labelling cellular nuclei of pain group are in the laminae I, II, V, VII, and X of the spinal cord the medial part of the frontal cortex (FC) and that of the EA group were in the trigeminal nucleus and the lateral area of the FC. The number of the labelling nuclei (n) of EA group war more than that of the pain group in the rostral ventromedical medulla, the lateral reticular, the solitary n. the popiaqueductal grey, the parafacicular n, the centromedian n. and the subparafascicular n, of the thalamus. 2. The labelling nuclei of EA and pain groups appear commonly in the dorsal raphe n., the locus ceruleus, the periventricular n. of the thalamus, the hypothalamue, the lateral habenular n., and the septal area. In the control animals, in general, the labelled nuclei were sparsely seen.
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PMID:[Expression of C-fos protein in CNS following electroacupuncture of the "quanliao" and the electrostimulation of the rat tail]. 808 74

Aversive behavior is produced by stimulating some brain structures, such as the dorsal periaqueductal gray and the medial hypothalamus. We have used c-fos immunoreactivity to map brain areas which are influenced by stimulation of these two structures. Stimulation was produced in freely moving rats by electrical stimulation or by microinjections of either excitatory amino acids or GABA blocking drugs. Behavior was monitored to detect emotional changes. The effects on labeling induced by the stimulation of either structure were then compared. Structures labeled include the amygdala, the stria terminalis, the supramamillary area, the hypothalamus, the periaqueductal gray, the superior colliculus, the nucleus cuneiformis, and the locus coeruleus. Regardless whether chemical or electrical stimulation was used or the structure stimulated, there was a large overlap among the brain areas labeled. We then compared our results with data from the literature where other methods of inducing aversion have been used, including pain and stress. There was remarkable similarity in the patterning of labeling irrespective of the type of stimulation (central-peripheral, chemical-electrical). There was, however, one interesting difference produced by central vs. peripheral stimulation. Labeling was unilateral in the former case and bilateral in the latter case. Our results suggest that there is a neural substrate that mediates aversive behavior, no matter how it is produced. Nevertheless, that peripheral stimulation produces mainly bilateral activation of this substrate whereas central stimulation produces mainly unilateral activation suggests that natural peripheral stimuli are also integrated at a higher functional level. Future work could be directed toward explicit comparisons of central versus peripheral stimulation to identify the structures involved in higher level integration of aversive behavior.
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PMID:What brain structures are active during emotions? Effects of brain stimulation elicited aversion on c-fos immunoreactivity and behavior. 813 52

Expression of the c-fos proto-oncogene in the rat brain was examined by immunostaining for fos, the nuclear protein product of the c-fos gene, after injection of interleukin-1-beta (IL-1 beta) into the gingiva of an incisor. The distribution pattern of labelled cells was compared with that induced by tooth pulp stimulation. Neurons that express fos-immunoreactivity (fos-IR) appeared in several regions in the neuraxis 1.5 h after IL-1 beta injection, peaked at 2 h, and then declined. Labelled cells were found bilaterally in regions that contribute to pain-relay and pain-inhibition. The distribution of labelled cells almost matched the pattern induced by noxious tooth pulp stimulation. In indomethacin-pretreated animals, no neurons expressing fos-IR were found in nuclei associated with relay of nociception nor in nuclei contributing to inhibition of nociception. The results suggest that a small amount of IL-1 beta at the site of periodontal disease can induce fos-IR in brain neurons through increased prostaglandin production.
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PMID:Expression of c-fos-like protein in the rat brain after injection of interleukin-1-beta into the gingiva. 819 34

Neurophysiological studies have generally failed to find evidence of a specific ascending pathway for visceral nociception. However, pain that arises from deep or visceral tissues typically differs from cutaneous pain, particularly in its diffuse, poorly localized quality. In this study, the c-fos mapping technique was used in order to investigate possible differences in the distribution of central neurons activated by afferent pathways from cutaneous and deep tissues that may be related to the differing quality of the sensations they evoke. The distribution of neurons in the upper cervical and medullary dorsal horn that displayed fos-like immunoreactivity (fos-LI) was examined following mechanical stimulation of dural blood vessels (transverse and superior sagittal sinuses), and was compared to that found following mechanical, thermal, and chemical stimulation of facial sites. Dural stimulation was carried out Brevital anesthesia in rats that had received a chronic surgical exposure of the transverse and superior sagittal sinuses 2 d earlier. Localized mechanical stimulation of the dural surface of the transverse sinus produced a predominantly ipsilateral increase in the number of fos-LI neurons in the medullary and upper cervical dorsal horn (primarily laminae I and V), and in the transition region between the trigeminal nucleus caudalis and interpolaris. Stimulation of the superior sagittal sinus produced increases in fos-LI labeling that were generally smaller than those produced by transverse sinus stimulation. The distribution of fos-LI labeling in the dorsal horn induced by dural stimulation differed from that induced by facial stimulation in two ways. (1) Dural stimulation produced a more diffuse distribution of fos-LI than facial stimulation in the dorsal horn. Whereas facial stimulation produced a dense, localized zone of fos-LI labeling in the dorsal horn, dural stimulation produced fos-LI labeling that extended from the midlevel of caudalis to C2/C3, and also extended across a large portion of the ventrolateral-to-dorsomedial axis of the dorsal horn. This distribution roughly corresponds to the representation of most of the dorsal half of the head and face. (2) Dural stimulation produced a more restricted laminar distribution of fos-LI labeling than facial stimulation, in that the dural-induced labeling in the superficial dorsal horn was primarily restricted to lamina I, whereas facial stimulation typically induced substantial labeling in both lamina I and the outer part of lamina II. These differences in the central organization of the afferent pathways from dural and facial sites may contribute to the differences in the quality of sensations evoked by these pathways.
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PMID:Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat. 820 85


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