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

Previous experiments have shown that noxious stimulation increases expression of the c-fos proto-oncogene in subpopulations of spinal cord neurons. c-fos expression was assessed by immunostaining for Fos, the nuclear phosphoprotein product of the c-fos gene. In this study, we examined the effect of systemic morphine on Fos-like immunoreactivity (FLI) evoked in the formalin test, a widely used model of persistent pain. Awake rats received a subcutaneous 150 microliters injection of 5% formalin into the plantar aspect of the right hindpaw. The pattern of nuclear FLI was consistent with the known nociceptive primary afferent input from the hindpaw. Dense labeling was recorded in the superficial dorsal horn (laminae I and IIo) and in the neck of the dorsal horn (laminae V and VI), areas that contain large populations of nociceptive neurons. Sparse labeling was noted in lamina IIi and in the nucleus proprius (laminae III and IV), generally considered to be nonnociceptive areas of the cord. Fos immunoreactivity was also evoked in the ventromedial gray, including laminae VII, VIII, and X. There was no labeling in lamina IX of the ventral horn. Since FLI was time dependent and distributed over several spinal segments, we focused our analysis where maximal staining was found (L3-L5) and at the earliest time point of the peak Fos immunoreactivity (2 hr). Twenty minutes prior to the formalin injection, the rats received morphine (1.0, 2.5, 5.0, or 10 mg/kg, s.c.) or saline vehicle. Two hours later, the rats were killed, their spinal cords removed, and 50 microns transverse sections of the lumbar enlargement were immunostained with a rabbit polyclonal antiserum directed against Fos. Prior treatment with morphine sulfate profoundly suppressed formalin-evoked FLI in a dose-dependent and naloxone-reversible manner. The dose-response relationship of morphine-induced suppression of FLI varied in different laminae. To quantify the effect of morphine on FLI, labeled neurons in sections taken from the L4/5 level of each rat were plotted with a camera lucida and counted. Staining in the neck of the dorsal horn (laminae V and VI) and in more ventral laminae VII, VIII, and X, was profoundly suppressed by doses of morphine which also suppress formalin-evoked behavior. Although the labeling was also significantly reduced in laminae I and II, at the highest doses of morphine there was substantial residual labeling in the superficial dorsal horn. These data indicate that analgesia from systemic opiates involves differential regulation of nociceptive processing in subpopulations of spinal nociceptive neurons.
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PMID:Systemic morphine suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord. 168 35

Noxious stimulation in vivo provokes the transcriptional activation of several genes which are thought to play an important role in the phenomena of stress and pain. In the rat, the expression of the c-fos proto-oncogene is rapidly induced upon noxious stimulation in defined neurons in the dorsal horn of the spinal cord. Interestingly, expression of the prodynorphin gene, which is thought to be involved in the endogenous mechanisms for pain/stress control, also localizes in the same anatomical area. Fos proteins are known to associate in transcriptional complexes with the products of the jun family constituting nuclear factor AP-1. These considerations prompted us to analyse the expression of the jun gene family members c-jun, jun B and jun D in rats subjected to noxious stimulation. We present data indicating that in unstimulated animals the transcripts of the three genes are differentially expressed and abundant within the various laminas of the lumbar spinal cord. Surprisingly, upon stimulation only the jun B transcript is augmented, being co-localized with Fos in a subset of neurons of the medial dorsal horn.
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PMID:Co-induction of jun B and c-fos in a subset of neurons in the spinal cord. 190 Mar 56

Noxious stimulation provokes the activation of genes that are thought to play a crucial role in the phenomena of stress and pain. Among these is the prodynorphin gene. By double-labeling in situ hybridization/immunohistochemistry, we show that increased prodynorphin gene expression is preceded, in the same neurons, by an early induction of c-fos. Inspection of the prodynorphin promoter region revealed the presence of several AP-1-like sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by the noncanonical TGACAAACA sequence, in which the palindromic structure is partly conserved by the 3' terminal CA dinucleotide. Transfection experiments in NCB20 neuroblastoma cells indicated that this site is a target of Fos/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes.
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PMID:Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene. 190 18

It has previously been shown that noxious and non-noxious peripheral stimuli induce c-fos expression in spinal dorsal horn neurons. In the present study we have examined the expression of c-fos in brainstem neurons following noxious chemical stimulation of the respiratory region of the nasal mucosa. In urethane-anaesthetized rats we injected mustard oil or applied CO2 pulses to the right nasal cavity. In control animals we applied paraffin oil or a continuous flow of air. A further group of control animals was anaesthetized and not subjected to any experimental treatment. Two hours after the first stimulus the rats were perfused with 4% phosphate-buffered paraformaldehyde. Brainstem sections were incubated with primary antiserum against the FOS protein and processed according to the ABC method. Only the mustard oil-treated rats had obvious signs of rhinitis and displayed FOS-positive cells in laminae I and II of the subnucleus caudalis and in the subnucleus interpolaris of the trigeminal brainstem nuclear complex as well as in the medullary lateral reticular nucleus. These areas are known to be involved in the processing of nociceptive information. Although CO2 pulses applied to the nasal mucosa are known to evoke pain sensations in man we did not observe any FOS-positive neurons in trigeminal and reticular brainstem areas of CO2-treated rats. This lack of c-fos expression probably results from the fact that unlike mustard oil, CO2 did not induce any apparent inflammatory reactions. In all animals c-fos expression was found in the nucleus of the solitary tract and in the area postrema. Staining in these areas might partly result from factors related to anaesthesia, changed respiration parameters and stress. Since the mustard oil-treated rats displayed the highest levels of immunoreactivity in the nucleus of the solitary tract and in the area postrema, additional effects specifically related to nociceptive input are very likely.
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PMID:c-FOS-like immunoreactivity in rat brainstem neurons following noxious chemical stimulation of the nasal mucosa. 190 66

The injection of dilute formalin results in a stereotyped nociceptive behavioral response. Administration of dextromethorphan (s.c.) but not saline, 30 min prior to intraplantar formalin injection prevents this nociceptive response in a dose-dependent manner. In addition, intraplantar formalin reliably induces c-fos mRNA in the ipsilateral spinal dorsal horn as assessed with quantitative solution hybridization at 30 min postinjection. No change in c-fos mRNA was detected in the contralateral spinal dorsal horn, nucleus raphe magnus, periaqueductal grey, medial thalamus, or sensorimotor cortex. Pretreatment with dextromethorphan at 60 mg/kg s.c., 30 min prior to formalin resulted in a suppression of c-fos induction, so that c-fos mRNA levels in the ipsilateral spinal dorsal horn of animals receiving dextromethorphan prior to formalin did not differ from controls. These data indicate that dextromethorphan suppresses formalin nociceptive behavior and one of the biochemical consequences of formalin nociception, i.e., induction of c-fos mRNA.
Pain 1995 Jun
PMID:Dextromethorphan suppresses both formalin-induced nociceptive behavior and the formalin-induced increase in spinal cord c-fos mRNA. 747 83

Experimental inflammation produced by an intraplantar injection of complete Freund's adjuvant results in local sensory hypersensitivity and up-regulates the neuropeptides substance P and calcitonin gene related peptide in the primary sensory neurons innervating the inflamed tissue. The inflammation also elevates nerve growth factor levels in the skin. Systemic administration of anti-NGF neutralizing antibodies prevent the behavioral sensitivity, the up-regulation of neuropeptides and the inflammation-induced expression of the immediate early gene c-fos in dorsal horn neurons, without modifying swelling and erythema. Elevation of the neurotrophin NGF in the periphery is a major contributor, therefore, of inflammatory pain.
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PMID:Nerve growth factor contributes to the generation of inflammatory sensory hypersensitivity. 753 Mar 42

Expression of immediate-early genes such as c-fos is thought to reflect patterns of neuronal activity in the central nervous system. Prolonged increases in Fos-protein-like-immunoreactivity (FOS-LI) are seen in the dorsal horn of adjuvant arthritic rats, and parallel increased pain behavior. Grafts of adrenal medullary, but not control tissue, into the spinal subarachnoid space reduce pain behavior and suppress the induction of spinal Fos-LI in arthritic rats. This reduction is particularly marked in superficial laminae (I-II), but is also significant in deeper laminae (III-IV and V-VI). The results of this study suggest that adrenal medullary transplants reduce spinal cord hyperactivation consequent to painful peripheral inflammation.
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PMID:Adrenal medullary grafts suppress c-fos induction in spinal neurons of arthritic rats. 756 45

We have attempted to define some of the patterns of expression of the IEG Fos in pain-related states. On one level, Fos may be used simply as marker of afferent stimulation and disease state, and in this respect Fos activation may be a useful tool after nociceptive stimulation to examine the effectiveness of different analgesic regimens. For example, certain analgesics such as opioids, alpha 2 agonists and local anaesthetics are more effective when given pre-emptively or early in the injury rather than later on. Furthermore, the persistent expression of Fos in the presence of high dose pre-emptive opioids is disturbing and yet it may explain variable success of studies attempting to show pre-emptive analgesia with opioid-based analgesic regimens. We suggest that Fos expression, as well as defining the magnitude and the duration of insult to the spinal cord seems also to signal the adaptive responses of the nervous system to nociceptive insult. Though we have focused on only one IEG, c-fos, and attempted to relate appearance to known functional changes within the spinal cord, there are in fact many more genes known to be upregulated with the same or slower kinetics (e.g. Fos B, FRA-1, FRA-2, Jun B, Jun D, NGFI-A). Increased understanding of the role of these genes is likely to lead to many novel targets in the search for normalization or restoration of spinal cord function in pain states and after nerve injury.
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PMID:Molecular biology of pain. 757 52

Central expression of the protooncogene c-fos was used to examine areas receiving noxious sensory input from the rat temporomandibular joint (TMJ). Fos-like immunoreactivity (Fos-LI) in the caudal brainstem was visualized 2 hours after unilateral injection of the small-fiber-specific excitant/inflammatory irritant mustard oil into the TMJ region. Control animals received injection of either mustard oil into the subcutaneous fascia overlying the masseter muscle or mineral oil vehicle into the TMJ region. In all groups, Fos-LI was consistently observed ipsilaterally in the spinal trigeminal nucleus and cervical dorsal horn and, bilaterally, in the nucleus of the solitary tract and the ventrolateral medulla. The expression of Fos-LI ipsilaterally in the paratrigeminal nucleus was variable. Within the trigeminal sensory complex, Fos-LI was restricted to subnucleus caudalis and the caudal portions of subnucleus interpolaris near the level of the obex. Approximately 12% of Fos-LI cells in subnucleus caudalis and in the cervical dorsal horn were found in laminae III-VI. Compared to TMJ mustard oil injection, mineral oil injection produced less Fos-LI at all rostrocaudal levels, whereas subcutaneous mustard oil injection produced less Fos-LI in caudal subnucleus caudalis but similar amounts in the cervical dorsal horn. Neither of these injections yielded significant ipsilateral responses in subnucleus caudalis, indicating that Fos-LI in this region following TMJ mustard oil injection could be ascribed solely to small-fiber stimulation in the deep TMJ region. The wide rostrocaudal distribution of Fos-LI within the caudal brainstem reflects the distribution of TMJ-responsive nociceptive neurons that may underlie the spread and referral of pain from the TMJ region.
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PMID:Distribution of Fos-like immunoreactivity in the caudal brainstem of the rat following noxious chemical stimulation of the temporomandibular joint. 764 5

Activation of the c-fos proto-oncogene following mechanical or chemical noxious stimulation of the urinary bladder was studied at T12-L2 and L5-S1, the spinal cord segments of projection of the hypogastric nerve (HGN) and pelvic nerve (PN) fibers, respectively. In intact adult rats, c-fos expression was found at T12-L2 only in lamina I. At L5-S1, Fos cells occurred in lamina I, the intermediolateral gray matter (ILG), and the dorsal commissure (DCM). These two areas contained the highest number of immunoreactive cells. Although more Fos cells were induced by mechanical than by chemical stimulation, the distribution of the reactive neurons was similar after both types of stimuli. In adult rats that had been treated neonatally with capsaicin, there was a marked fall in c-fos activation by mechanical or chemical noxious stimuli in all immunoreactive areas. The loss of Fos cells was more pronounced in ILG and DCM at L5-S1 (95%) than in lamina I at the two spinal domains (70%). The confinement of c-fos activation to lamina I at T12-L2, the spinal cord domain of the HGN, suggests that the input carried from the bladder by this nerve is preferentially used for pain perception. The same function is expected for noxious input reaching lamina I at L5-S1, the spinal cord territory of termination of the PN. However, the striking number of Fos cells in ILG and DCM supports the important role played by this nerve in the control of the micturition reflex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of the c-fos proto-oncogene in the spinal cord following noxious stimulation of the urinary bladder. 777 9


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