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

Expression of the c-fos gene in CNS induced by formalin injection into the face as pain stimulus was examined in cats. Fos-positive neurons were demonstrated in the anterior cingulate, anterior insula and other areas of the cerebral cortex bilaterally, midline thalamic nuclei, hypothalamus, and brainstem in both the formalin-injected and control group (anesthesia only). Most of these labeled regions appeared to correspond to stress- and anesthesia-related sites. The difference from the control was the finding of Fos-positive cells in the SI, possible SII and trigeminal subnucleus caudalis in the experimental group. Almost significant increase in Fos-positive cells was also observed in areas 24, 23 and the anterior agranular insular cortex in experimental cats. Our findings appear to be compatible with recently reported PET findings in man, except laterality. For full appreciation of the complex pain experience, these diverse areas of the brain appear to be activated.
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PMID:c-fos expression after formalin injection into the face in the cat. 891 46

The superior colliculus (SC) has an established role in the sensory guidance of motor commands required to orient an animal towards novel stimuli. In addition to the representations of visual, auditory, and somatosensory stimuli, the SC also contains a large population of nociceptive neurones. The purpose of the present investigation was to see if nociceptive neurones in the SC can be characterised with c-fos immunohistochemistry as a prelude to establishing anatomical connectivity with specific target regions in the brainstem. To ensure comparability with previous electrophysiological investigations, the present study was conducted in animals anaesthetised with urethane. A series of independent issue relating to basic aspects of experimental protocol were investigated. The principal findings were: (i) Despite minimising the exposure of animals to extraneous stimuli, basal levels of immunostaining were observed. (ii) Urethane anaesthesia induced an increase in Fos-like immunoreactivity (FLI) over the basal condition. (iii) No additional labelling was induced by non-noxious tactile stimulation of the hindpaw. (iv) Unilateral noxious mechanical stimulation elicited a reliable increase in FLI over all control conditions. (v) This increase in FLI was expressed bilaterally and restricted largely to the intermediate white layer. (vi) The induction of FLI was related to noxious stimulation intensity. (vii) No reliable differences in the spatial topography of FLI expression were observed when unilateral noxious mechanical stimulation was administered to the face or hind foot. (vii) A higher level of urethane anaesthesia had a generally suppressive effect on FLI expression. (ix) There were no differences in the distribution of FLI induced by noxious mechanical or noxious chemical stimulation. (x) The increase in FLI induced by noxious pinch was abolished by a naloxone reversible pre-treatment with morphine. These data confirm that c-fos immunohistochemistry can be used to characterise nociceptive cells in the rat superior colliculus, and generally complement recent electrophysiological data. The identification of nociceptive cells in the stratum album intermediale, the source of collicular input to regions of the contralateral brainstem involved in orienting, suggests the SC may play a significant role in the localisation of pain.
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PMID:Analysis of nociceptive neurones in the rat superior colliculus using c-fos immunohistochemistry. 893 Jul 88

Fos-immunoreactivity can readily be induced in spinal cord neurones by noxious, but to a much more limited extent, by innocuous peripheral stimuli. The present study has investigated whether low intensity stimuli and electrical stimulation of A beta afferents elicit greater c-fos expression during the behavioural sensory hypersensitivity generated by experimental peripheral inflammation. We have examined the time-course of c-fos expression after inflammation produced by either an intra-plantar injection of the irritant turpentine oil or of complete Freund's adjuvant (CFA). In the former case, a significant initial expression in all dorsal horn laminae was followed by a gradual decrease, whereas after CFA injection, an initial expression limited to the superficial laminae subsequently extended into the deep laminae, with a decrease at 24 h and an increase in labelling at later times. Low intensity touch stimuli repeated for 10 min, when applied at 24 h and 48 h after CFA injection, elicited a significant increase in the number of Fos-immunoreactive neurons in both the superficial and deep laminae of the dorsal horn compared to non-inflamed animals. Electrical stimulation of the sciatic nerve 24 h post-CFA injection, at a strength sufficient only to activate A beta-afferents fibres (100 microA, 50 microseconds, 10 min), also elicited a significant increase in labelling relative to the same stimuli applied in control animals, especially in laminae V-VI. The present results demonstrate that low intensity cutaneous stimuli elicit a significantly greater increase in c-fos expression in dorsal horn neurons during peripheral inflammation and that A beta-afferent input contributes to this, a finding that may relate to the allodynia experienced during inflammation.
Pain 1996 Oct
PMID:Basal and touch-evoked fos-like immunoreactivity during experimental inflammation in the rat. 895 24

Inflammation of the temporomandibular joint (TMJ) region evokes pain and hyperalgesia as well as causing persistent changes in the response properties of central trigeminal neurons. To determine if excitatory amino acids have a role in TMJ-induced responses, extracellular concentrations were measured in microdialysate samples from probes positioned in the spinal trigeminal nucleus (Vsp) near the transition region between subnucleus interpolaris and subnucleus caudalis (Vi/Vc) in chloralose-anesthetized rats. Injection of the selective small fiber excitant, mustard oil (20 microliters, 20% solution), into the ipsilateral TMJ region caused a transient (by 10 min) increase in glutamate (from 0.48 +/- 0.16 to 1.94 +/- 0.78 microM, P < 0.005) and aspartate (from 0.29 +/- 0.11 to 1.78 +/- 0.82 microM, P < 0.025) among sites located at the ventrolateral pole of the Vi/Vc transition region (n = 6). Samples from probes located within the ventral Vsp, but outside this Vi/Vc transition region (n = 9), did not show significant changes in amino acid concentrations. Glutamate and aspartate also increased after mustard oil injections into the contralateral TMJ region. Dialysate concentrations of serine and taurine did not change significantly after mustard oil injections. Addition of high potassium (150 mM) to the perfusate solution caused increases in glutamate and aspartate regardless of probe location. The transient and selective release of glutamate and aspartate within the Vi/Vc transition after acute irritation of the TMJ region is consistent with a proposed role for excitatory amino acids in mediating noxious sensory input from deep orofacial structures. Together with previous reports of c-fos expression, these results suggest that neurons within the ventrolateral portion of the Vi/Vc transition may serve as a relay site for the integration of sensory or reflex responses to acute inflammation of the TMJ region.
Pain 1996 Oct
PMID:Excitatory amino release within spinal trigeminal nucleus after mustard oil injection into the temporomandibular joint region of the rat. 895 41

The present study was conducted to demonstrate immunohistochemically, the sites of c-fos protein expression in the brains of mice subjected to acute and chronic social defeat stress. To induce social stress, mice were placed in situations of species-specific intermale aggression either only once or five times at 24 h intervals. Two hours after the single or fifth defeat stress, many c-fos immunoreactive neurons were observed in a variety of brain regions including the limbic system and sensory relay nuclei. The c-fos immunoreactive neurons in the brains of acute defeat mice decreased in number with time and the c-fos staining pattern of acute defeat mice became indistinguishable from that of normal control mice by 24 h after the single defeat stress. In contrast, chronic defeat stress induced persistent c-fos expression in the forebrain and brainstem even 24 h after the fifth defeat stress. In the forebrain of chronic defeat mice, the olfactory bulb, cingulate cortex, hippocampus, entire hypothalamus, septal nuclei and the amygdaloid complex, except for the central nucleus, were labeled intensely with c-fos antiserum. In the lower brainstem, nerve cells with c-fos immunoreactivity were seen mainly in ascending and descending sensory relay nuclei relevant to auditory and vestibular transmission, epicritic sensation (gracile and external cuneate nuclei), pain inhibition (central gray and raphe nuclei), and viscerosensory transmission (solitary tract nucleus). The differences in c-fos expression among the normal control, acute and chronic defeat mice were evaluated by an enumeration of the immunopositive neurons within each brain nucleus examined, and they were confirmed subsequently by statistical analysis. There was little c-fos expression in the nucleus putamen, lateral, ventral and posterior thalamic nuclei, pretectal nuclei, medial geniculate nucleus, red nucleus, substantia nigra, cerebellum, spinal cord, or cranial nerve nuclei. These findings suggest that chronic but not acute defeat stress causes persistent c-fos expression in more widespread brain regions than do any other stresses so far investigated. The present study may shed light on the central mechanisms by which behavioral abnormalities and/or chronic sociopsychological stress leads to the occurrence of abnormal behavior and/or psychosomatic disorders in experimental animals and humans.
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PMID:Persistent c-fos expression in the brains of mice with chronic social stress. 895 78

We have assessed the effects of intraplantar local anaesthetics (bupivacaine and lignocaine) on carrageenan-induced oedema, mechanical allodynia and spinal c-fos protein expression. Mechanical allodynia was evaluated using the vocalization threshold to paw pressure (VTPP) every 30 min until 60, 180 or 240 min after administration of carrageenan. Peripheral oedema, mechanical allodynia and spinal c-fos protein expression were maximal 180 min after carrageenan. Lignocaine did not influence either oedema or VTPP, but reduced spinal c-fos expression at 60 min after carrageenan without later effects. Bupivacaine induced an increase in VTPP at 30 and 60 min, limitation of oedema at 60 min and a reduction in spinal c-fos expression at 60 and 180 min, but these effects were not present 240 min after carrageenan. Intraplantar infiltration with lignocaine and bupivacaine before carrageenan transiently limited signs of inflammatory pain but did not prevent them.
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PMID:Effects of local anaesthetics on carrageenan-evoked inflammatory nociceptive processing in the rat. 895 83

Gamma-aminobutyric acid (GABA) receptors are ubiquitous inhibitory receptors in the central and peripheral nervous systems. Valproic acid (2-propylpentanoic acid), which enhances GABA synthesis and blocks degradation, is useful in migraine treatment and may act through activation of GABA receptors to modulate trigeminal nociceptive neurons innervating the meninges. To investigate this possibility, we tested the effect of valproate and allopregnanolone, a metabolite of progesterone, which binds and modulates the GABA receptor in an animal model of cephalic pain. One hundred ten Hartley guinea pigs were pretreated with either valproate or allopregnanolone 30 minutes prior to activation of trigeminal afferent fibers via intracisternal injection of the irritant, capsaicin. The effects of valproic acid and allopregnanolone were examined on c-fos expression within the trigeminal nucleus caudalis (lamina I, II), the termination site for small unmyelinated C fibers projecting from the meninges. C-fos positive cells were counted at three representative levels (rostral, middle, and caudal) by an observer naive to the treatment group. We found that valproate (> or = 10 mg/kg, IP) reduced labeled cells by 52% (P < 0.05) and allopregnanolone (> or = 100 mg/kg, IP) reduced labeled cells by 42% (P < 0.01). Bicuculline (GABAA antagonist), but not phaclofen (GABAB antagonist), blocked the valproate effect, thereby documenting the importance of GABAA receptors. We conclude that the attenuation of c-fos-LI by valproate and allopregnanolone is mediated via GABAA receptors. These studies complement prior experiments showing that valproic acid and allopregnanolone block neurogenic inflammation within the meninges via GABAA receptor-mediated mechanisms. The findings suggest a potential strategy for discovering new antimigraine drugs with high affinity for the GABAA receptor and its modulatory sites.
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PMID:Wolff Award 1996. The actions of valproate and neurosteroids in a model of trigeminal pain. 899 May 96

Injection of formalin in the rat hindpaw produces two phases of nociceptive behavior. Although it is generally agreed that the first phase results from direct chemical activation of nociceptive primary afferent fibers, the factors that contribute to the second phase are not established. In the present study, we monitored the expression of the c-fos protein to evaluate whether the pattern of activity of dorsal horn neurons differs as a result of ongoing afferent activity during the two phases. To selectively block the first or second phase, we respectively used remifentanil, a potent and short acting opiate agonist, and QX-314, a quaternary derivative of lidocaine, which does not cross the blood brain barrier. We also evaluated the effect of eliminating nociceptive behavior in both phases using both remifentanil and lidocaine or a combination of local anesthetics, bupivicaine and quaternary lidocaine. In all groups, formalin (5%, 50 microliters) was injected subcutaneously into the plantar surface of the hindpaw. To assess the nociceptive behavior produced by formalin, we monitored the number of flinches. Injection of remifentanil during the first phase completely blocked the first phase formalin-evoked nociceptive behavior, and had no effect on the second phase. Injection of lidocaine during the interphase completely blocked second phase nociceptive behavior. As expected, when remifentanil was administered during the first phase and lidocaine during the second phase, all formalin-evoked nociceptive behavior was blocked. The same was true for rats that received injections of bupivicaine and lidocaine during phases 1 and 2, respectively. In laminae I-II of the L4-L5 segment, the magnitude of the decrease in Fos expression was comparable for remifentanil (26.5%) and lidocaine (27.3%); the decrease was greater when both remifentanil and lidocaine were administered (50.5%), and even greater when bupivicaine and lidocaine were used (74.2%). In laminae V-VI, remifentanil, by itself, decreased c-fos expression by 39.4%; for lidocaine alone, the decrease was 58.4%. We did not observe further significant decreases when both remifentanil and lidocaine, or bupivacaine and lidocaine were injected (69.7% and 74.6%, respectively). Our results not only provide strong evidence that activity during the second phase is necessary for maintaining the maximal expression of c-fos in the spinal cord, but also reveal significant regional differences in the central patterns of activity generated during the two phases. These results also confirm our previous reports that c-fos expression is not eliminated when the behavioral manifestation of the noxious stimulus is completely blocked.
Pain 1997 Jan
PMID:Differential contribution of the two phases of the formalin test to the pattern of c-fos expression in the rat spinal cord: studies with remifentanil and lidocaine. 906 19

An understanding of migraine must be based on data concerning the anatomy and physiology of the painsensitive intracranial structures. Stimulation of the superior sagittal sinus produces changes in brain blood flow and changes in neuropeptide levels similar to those seen in humans during migraine. To better understand the anatomy of the central ramifications of pain-sensitive intracranial structures we have examined the distribution of c-fos immunoreactivity in the monkey when the sinus is stimulated. Six adult Macaca nemestrina monkeys were anaesthetised. The superior sagittal sinus was isolated after a midline craniotomy and a paraffin well created. At 24 h after completion of the surgery the sinus was stimulated electrically for 1 h and the brain subsequently removed and processed for c-fos. In control animals in which the sinus was isolated but not stimulated there was a small amount of c-fos expression in the caudal brainstem and upper cervical spinal cord. Stimulation of the superior sagittal sinus evoked expression of c-fos in the caudal superfical laminae of the trigeminal nucleus and in superficial laminae of the dorsal horn of the C1 level of the upper cervical spinal cord. A lesser amount of c-fos was seen at C2 while no significant labelling above control was observed at C3. These data, while largely confirming the results from the cat concerning the central distribution trigeminovascular afferents, underscore a possibly unique specialisation of trigeminovascular afferents at the C1 level. Given the close evolutionary relationship of the monkey to man it is likely that the cells described in this study represent for primates the nucleus that mediates the pain of migraine.
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PMID:The distribution of trigeminovascular afferents in the nonhuman primate brain Macaca nemestrina: a c-fos immunocytochemical study. 914 23

We had previously demonstrated that c-fos antisense oligodeoxynucleotides dose-dependently suppressed formalin-induced c-Fos protein and behavioral hyperalgesia. To test whether de novo protein synthesis is required for the development of persistent pain after peripheral inflammation, we observed formalin-induced spinal c-Fos protein and nociceptive behaviors following pretreatment with cycloheximide, a protein synthesis inhibitor. Cycloheximide dose-dependently inhibited formalin-induced spinal c-Fos protein and tonic nociceptive responses. The possible non-specific effects other than protein synthesis inhibition on nociceptive behavior were carefully discussed and excluded. These results provide further support to the hypothesis that de novo protein synthesis is essential for the development of behavioral hyperalgesia.
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PMID:Protein synthesis inhibitor cycloheximide dose-dependently decreases formalin-induced c-Fos protein and behavioral hyperalgesia in rats. 918 Feb 13


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