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

1. The aim of this review is to consider the relative roles of inhibitory and excitatory amino acid receptor-mediated events in the processes leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and glutamate, and how the relative balance between activity in these systems appears to determine the level of pain transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. It has been shown that activation of this receptor underlies wind-up, whereby the level of transmission of noxious messages is potentiated. Antagonists at this receptor-channel complex prevent or block enhanced (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step toward understanding why and how a painful response is not always matched to the stimulus. Such events have parallels with other plastic events such as long-term potentiation (LTP) in the hippocampus. 5. However, the roles of inhibitory transmitter systems can also change insofar as opioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-documented and discussion will center on whether this has clinical implications. 7. In addition to behavioral and electrophysiological approaches to the pharmacology of pain the current status of the use of markers of early onset genes such as c-fos, as monitors of activity, will be discussed. 8. Hyperalgesia would appear to be balanced by inhibitions during inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may predominate, whereas they are held in check by inhibitions under conditions of inflammation.
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PMID:The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. 918 94

c-fos antisense strategy was applied as a pharmacological approach to characterize its dose-dependent role and reversibility in the reduction of formalin-induced hyperalgesia. Nociceptive behavioral responses (weighted score, flinching response, licking/biting) following formalin (50 microl 5%) injection were assessed in adult Wistar rats receiving different doses (50 nM, 250 nM) of intrathecally administered c-fos antisense oligodeoxynucleotides at different times prior to formalin injections. The treatments dose dependently decreased both Fos immunoreactivity expression in dorsal horn of rat lumbar spinal cord and all nociceptive measures in the tonic phase of the formalin test. c-Fos correlated well with weighted pain score and/or flinching responses, but not with licking/biting behavior. With the exception of a 48-120 h period required for licking/biting behavior to be restored to its normal status, the suppressive effect on c-fos expression and other nociceptive behaviors disappeared 48 h following c-fos antisense oligodeoxynucleotide treatment. The results suggest a pharmacological potential of c-fos antisense oligodeoxynucleotides in the central nervous system to block immediate-early genes and their resulting physiological consequence following noxious stimulus.
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PMID:Intrathecally administered c-fos antisense oligodeoxynucleotide decreases formalin-induced nociceptive behavior in adult rats. 921 79

Cortical spreading depression (CSD) is characterized by a transient, reversible depression of EEG activity which advances across the cortical surface at a velocity of 2-5 mm/min. CSD was originally linked to the aura phase of migraine, but recently also to migraine headache. The theory is that CSD activates meningeal trigeminal C-fibers causing neurogenic inflammation and pain (Moskowitz, M.A., Nozaki, K. and Kraig, R.P., Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms, J. Neurosci., 13 (1993) 1167-1177). The present study is an examination of the proposed link between CSD elicited in rats and activation of trigeminal nerve fibers. Multiple CSDs were elicited unilaterally for 1 h by KCl injections (1 M, 5 microliters) into the right hemisphere, while NaCl (1 M, 5 microliters) was injected into the left as control. After an additional 1 h the animals were sacrificed and trigeminal activation assessed by the expression of c-fos in trigeminal nucleus caudalis (TNC) using immunohistochemistry. The correlation between the number of CSDs and the extent of c-fos expression was determined. In addition the effect of sumatriptan (0.3 mg/kg) and morphine (3 mg/kg) given i.v. 30 min before elicitation of CSD was evaluated. CSD caused increased c-fos expression in lamina I and II of TNC where C-fibers, end, the response being greater ipsilaterally. Morphine, but not sumatriptan, reduced c-fos expression in both the ipsilateral and contralateral TNC by 71% (P < 0.05 and P = 0.19, respectively), confirming that nociceptors have been activated. No positive correlation was seen between the number of CSDs and the extent of c-fos expression in TNC. Instead we observed a positive, linear correlation between the number of KCl injections and the extent of c-fos expression in TNC (correlation coefficient r = 0.709, P < 0.05). We suggest that the C-fiber activation observed is caused by hyperosmolar KCl/NaCl and not CSD. Hence, our results do not support the hypothesis of Moskowitz et al. (Moskowitz, M.A., Nozaki, K. and Kraig, R.P., Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms, J. Neurosci., 13 (1993) 1167-1177) which links CSD with migraine headache.
Pain 1997 Sep
PMID:Possible mechanism of c-fos expression in trigeminal nucleus caudalis following cortical spreading depression. 969 82

Using pain measurement and immunohistochemistry, we have observed that the intrathecal injection (it) SP produced dose-related pain response. A larger dose of SP (5 micrograms, 10 micrograms) could reduce the pain threshold and evoke c-fos expression, but no obvious effect was produced by a smaller dose of SP (0.5 microgram, 1 microgram). Morphine (it) not only increased the pain threshold, but also inhibited pain response and c-fos expression of spinal cord induced by it SP, the effects could be reversed by naloxone.
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PMID:[Effect of morphine on pain threshold and C-fos expression induced by substance P]. 938 60

Nociception is a protective system of the body which prevents it from injury and tissue damage. Human beings respond to noxious stimuli by moving away. They learn by pain to avoid these situations in future. Shortly after major injury, there is a limited analgesic period allowing the body to flee the area of danger, later on, emerging pain compels the body to rest and supports recuperation. While acute pain has a certain meaning, chronic pain does not. It induces a comprehensive suffering including loss of initiative, appetite and vigilance. It reduces life-quality, often accompanied by depressive moods. Acute pain causes changes in the central nervous system leading to an increased sensitivity of nociception (hyperalgesia). During healing, the central processing of noxious stimuli is normalised taking minutes to weeks. Sometimes, unknown factors initiate chronification of pain. Changes on a molecular level in peripheral tissue as well as in the central nervous system induce "cellular early genes", a synthesis of c-fos, c-jun and other proteins favouring the chronification of pain. All efforts have to be made to depress or interrupt such a development. One of the first steps to pain prophylaxis in a hospital is an optimal surgical technique: incision, extension, limited tissue damage and minimal invasive surgery should guarantee the smallest impairment of the nociceptive system possible. However, nociceptive input is intense and of long duration and leads to central sensibilisation. Postoperative pain has lost its function as surgery anticipates healing. Pain induces a reduction of ventilation, circulation, digestion and increases the risk of other disorders. There is need of aggressive pain treatment for humanitarian reasons and for reasons of late sequelae like permanent pain and increased reduction of function. This is of pivotal importance in patients with amputations or sympathetic reflex dystrophy (SRD). Antinociception is best provided by regional anaesthesia technique with a combination of local anaesthetics and opioids which results in better outcome. Hence, regional anaesthesia techniques are strongly indicated in those patients. Good antinociception may be even more important than it is assumed today. Anand demonstrated a lower morbidity and mortality in 45 newborns undergoing cardiothoracic surgery, when general anaesthesia was performed with high-dose sufentanil versus halothane supplementary doses of morphine. Anaesthesiologists have to reconsider the quality of general anaesthesia: the antinociception of their regimen.
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PMID:[Neurophysiological aspects of pain and its consequences for the anesthetist]. 941 70

We have used a partial sciatic nerve ligation model to examine the time course for changes in the expression of mRNA for three peptides related to pain transmission at spinal sites (dynorphin, enkephalin and substance P), during the development of allodynia. Enhanced expression of mRNA for dynorphin and substance P was observed in the dorsal horn on the same side as the partial nerve ligation. Increased expression of dynorphin mRNA was biphasic. The initial increases in expression of dynorphin mRNA occurred at 3 h, and a secondary peak was observed 1-3 days after surgery. The secondary increases coincided roughly with increased substance P mRNA expression. However, both dynorphin and substance P mRNA returned to control values after 1 week despite continuing allodynia. No significant changes in expression of mRNA for enkephalin were observed. The elevation of substance P mRNA in intrinsic spinal cord neurons may be secondary to changes in immediate early genes c-fos and jun-B, whereas the expression of dynorphin and enkephalin mRNA is differently regulated. The results also suggest that changes in the expression of the three neuropeptides are not critically involved in the development and maintenance of chronic pain or allodynia.
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PMID:Temporal changes in spinal cord expression of mRNA for substance P, dynorphin and enkephalin in a model of chronic pain. 942 59

Just over a decade has past since Hunt et al. reported that the gene c-fos and its protein product Fos are expressed in the spinal cord of rats subjected to peripheral noxious stimulation. These authors showed that noxious stimulation (application of radiant heat or mustard oil) to the hind paw resulted in a massive increase in the expression of Fos in neurons in the dorsal horn of the lumbar spinal cord. Since then, there has been an explosion of studies in which c-fos has been used to study nociception (pain), and the number of such studies increases each year. The net result has been to establish c-fos expression as a valuable tool in pain research. Moreover, recent studies have provided evidence identifying the role of c-fos expression in spinal nociceptive processes. However, there are several important limitations to the practice of using c-fos to study nociception, and these limitations can be easily overlooked as the practice graduates to the status of an established technique. The increasing use of c-fos to study nociception necessitates a critical review of the practice, identifying the shortcomings as well as the strengths of this tool.
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PMID:Using c-fos as a neural marker of pain. 943 95

The maturational status of Adelta and C-fibers in the fetal rat spinal cord was examined using formalin-induced c-fos expression as a marker for neuronal activities. Awake 19-, 20-, and 21-day fetuses (FD) were injected ex utero with 5 microl of 10% formalin either into the ventral aspect of the forepaw or the hindpaw. FD 19 fetuses showed little response to the injection, but with increasing age, the fetuses exhibited more specific behaviors following injury of the paw. By FD 21, fetuses treated with formalin injection showed body curls and twitches, mouth opening, face wiping, and withdrawal of the injected paw. The anatomical data paralleled that of behavior; FD 19 animals expressed a small number of Fos labeled nuclei following the formalin injection that was not statistically different from control animals. The formalin-induced increase in Fos staining was first observed at FD 20 with a large increase in the number of Fos labeled cell occurring between FD 20 and 21. By FD 21, the pattern of Fos stained nuclei resembled that found in neonatal rats. There was constitutive bilateral staining in all untreated, saline and formalin injected fetuses that is unique to prenatal animals. Formalin treated fetuses showed constitutive level of staining in addition to the increase in the c-fos expression caused by formalin. We have thus demonstrated that, as indexed both by behavioral response and by Fos immunoreactivity, rat fetuses are capable of transmitting and responding to noxious input before birth.
Pain 1997 Dec
PMID:Formalin-induced c-fos expression in the spinal cord of fetal rats. 946 24

The sites of renal pain processing in the rat spinal cord were studied by mapping the spinal cord neurons expressing c-fos after acute ureteral distension due to obstruction. A new experimental model is presented. A nylon knot was loosely placed around the ureter and the ends of the thread exteriorized through the retroperitoneal wall. Eight days later, when all c-fos expression due to nociceptive input from the abdominal wound and the manipulation of the intestines had disappeared, the nylon ends were pulled to produce ureteral occlusion. C-fos activation occurred at spinal segments T10-L4 with a peak at L1-L2. The activated neurons were concentrated in laminae I, lateral IV-V, medial VII and X. While in lamina I nearly all Fos-immunoreactive cells were ipsilateral, in the deeper laminae taken together 60% cells were ipsilateral and 40% contralateral to the distended ureter. It is suggested that renal nociceptive input giving rise to conscious pain perception is transmitted through ipsilateral lamina I, whereas input triggering autonomic reflexes may be mainly processed, ipsi- and contralaterally, in the deep laminae.
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PMID:Sites of renal pain processing in the rat spinal cord. A c-fos study using a percutaneous method to perform ureteral obstruction. 947 Jan 45

Peripheral noxious stimulation is known to trigger signalling cascades in neurons of the spinal cord. The response to pain and stress at the level of gene expression involves transcriptional activation of several cyclic AMP responsive genes. Here, we show induction of the CREM (cyclic-AMP responsive element modulator) gene in distinct subpopulations of spinal cord neurons upon thermal noxious stimulation. The addition of forskolin or glutamate to cultured spinal cord neurons results in the induction of the CREM isoform, ICER (Inducible cyclic-AMP Early Repressor), a powerful repressor of cAMP-induced transcription. Overexpression of ICER in cultured spinal cord neurons results in the repression of the c-fos and c-jun promoters induced by forskolin and glutamate. On this basis, we postulate that early activation of ICER in spinal cord participates in the attenuation of early gene induction following noxious stimulation.
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PMID:Peripheral noxious stimulation induces CREM expression in dorsal horn: involvement of glutamate. 951 83


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