Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rib fractures (RFs) are estimated to be present in 10 per cent of all traumatic injuries. However, up to 50 per cent of all fractures go undetected on the screening chest X-ray (CXR). The purpose of this study was to identify the incidence of clinical (CRFs) and objective rib fractures (ORFs) as well as to examine the utility of the routine follow-up CXR with regard to patient recovery and healthcare cost. We identified patients sustaining RF in addition to other traumatic injuries with an Injury Severity Score (ISS) < or = 15 and RF as the primary pathology. Five hundred fifty-two patients sustained blunt thoracic trauma with resultant RF. Two hundred nine patients had RFs and an ISS < or = 15. The average ISS was 8. Follow-up films illustrated that 93 per cent of CRFs had resolution of any pathology, 4 per cent had persistent X-ray findings, and 4 per cent were lost to follow-up. Ultimately 93 per cent of patients with CRF were able to resume daily activities without disability and 3 per cent incurred lifestyle changes at home or work, which was significantly better than those with ORFs (P < 0.05). Follow-up films produced no change in clinical management and cost approximately $2000/year. The prognosis for CRFs is excellent if treatment consists of appropriate pain management and pulmonary rehabilitation. We do not advocate routine follow-up CXRs in addition to physical examination for the evaluation of CRFs unless clinical deterioration is evident.
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PMID:Clinical rib fractures: are follow-up chest X-rays a waste of resources? 1201 89

Early preterm neonates in the Neonatal Intensive Care Unit (NICU) are subjected to repeated painful procedures which could sensitize their responses to pain and potentiate neuroendocrine and behavioral responses to subsequent stressors in the long-term. In this study, we used the model of the neonatal rat to test the effects of repeated pain during the first 2 weeks of life on neuroendocrine responses (CRF, ACTH and corticosterone) to stressors varying in intensity and on maternal behavior in the postnatal period. To closely mimic the type of repeated painful stimulus experienced by preterm neonates (i.e., heelstick), neonatal rats aged day 2-14 were submitted daily to having their rear heels warmed to 34 degrees C and pricked (handled and pain, HP) or not (handled, H) with a needle. For the procedure, all pups were separated from their mothers for a total period of 15 min and reunited afterwards. Unhandled (UH) pups not subjected to daily maternal separation were used as controls. On days 6 and 12, litters from the HP and H groups were videotaped for 90 min upon return with the mother and maternal behavior was analyzed. Frequency of ultrasonic vocalizations (USV) were recorded during the procedure and upon return of pups with the mother. On day 15 and 20, rat pups from all groups were exposed to a 3-min ether vapor stressor or to an openfield for 10 min. Plasma ACTH and corticosterone concentrations were determined at 0, 5, 30, 60 and 120 min after stress onset. Our results show that repeated pain did not modify body weight of the pups, however, on day 6 of life, maternal pup grooming was increased significantly (P<0.05) in the HP group compared to the H group. Frequency of USV was not changed between H and HP rats either during the separation or after reunion with the mother. Plasma ACTH and corticosterone levels under basal or stimulated conditions were not different between UH, H and HP groups. However, the UH pups showed a tendency towards higher ACTH secretion after stress compared to H and HP groups. These results suggest that repeated pain during the first 2 weeks of life in the rat does not lead to significant changes in stress responsiveness in 2-week-old pups, but we suggest that changes in mother-pup interaction (increased grooming) might act as a buffer on the cumulative effect of pain on stress responsiveness.
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PMID:Repeated neonatal pain influences maternal behavior, but not stress responsiveness in rat offspring. 1258 30

Tissue damage causes an inflammatory response in which cytokines contribute to a painful state. Local inflammation also leads to an enhanced expression of opioid peptides such as END within immune cells of inflamed tissue. These endogenous substances can be released by "releasing factors" such as CRF and IL-4 via activation of their receptors on the cell surface of inflammatory cells. Local application of CRE or IL-1 into inflamed tissue results in significant analgesia which is most likely mediated by a release of opioid peptides from immune cells within inflamed tissue. This mechanism of pain inhibition also seems to have a physiological role. Upon certain stressful stimuli analgesic effects seem to be mediated by a release of opioid peptides and a subsequent activation of peripheral opioid receptors. Locally expressed CRF but not IL-1 appear to trigger this release. Thus, inflammatory pain can be modulated both by exogenous CRF and IL-1 as well as endogenous CRF. These mechanisms are based on interaction between the immune and nervous systems. Both the initiation of pain and its control can be regarded as the body's response to prevent further injury, to support wound healing and to return to a normal function as quickly as possible.
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PMID:Cytokines and peripheral analgesia. 1261 63

The immune system is a source of opioid peptides and plays an important role in the control of inflammatory pain. Inflammation not only increases the opioid receptor expression in DRG neurons but also enhances transport and accumulation of opioid receptors on the peripheral terminals of sensory neurons. Immune cells containing opioid peptides migrate to the inflamed tissue. This is orchestrated by adhesion molecules up-regulated on vessel endothelia and co-expressed by opioid-containing immunocytes. The peptides are secreted by stressful stimuli, CRF and cytokines and the corresponding receptors are present on opioid-expressing leukocytes. The opioids bind to their receptors localized on peripheral sensory nerves leading to pain inhibion. In the more distant future, these findings might stimulate the development of novel analgesics based on enhancing the transport and release of immune-derived opioid peptides into injured tissue.
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PMID:Morphological correlates of immune-mediated peripheral opioid analgesia. 1261 66

We aimed to characterize neuronal and corticotrophin-releasing (CRF) pathways in a model of somato-visceral pain in rats. Male rats received an intraperitoneal (i.p.) injection of either vehicle (controls) or acetic acid (AA) and were sacrificed 1, 2, 3, 4, or 6 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF(1), CRF(2 alpha,beta) receptors were assayed by in situ hybridisation histochemistry. Localization of these transcripts within CRF-immunoreactive (i.r.) neurons of the paraventricular nucleus (PVN) of the hypothalamus was also determined. AA i.p. induced c-fos mRNA expression in brain nuclei involved in the autonomic, behavioural and neuroendocrine response to pain. Some of these nuclei are involved in the control of digestive motility, as represented by the PVN, locus coeruleus and nucleus tractus solitarius. CRF pathways, in particular in the PVN, are activated in this model. Indeed, a robust signal of c-fos and CRF(1) transcripts was observed in the PVN and numerous CRF-i.r. neurons expressed c-fos or CRF(1) transcripts in the PVN of AA-treated animals. In contrast, no expression of CRF(2) transcripts was observed in the PVN either in basal conditions or after AA i.p. These data argue for an activation of CRF pathways within the PVN in this model of somato-visceral pain. The use of CRF antagonists, particularly of the CRF(1) type, should have an interest in somato-visceral pain pathology.
Pain 2004 Aug
PMID:c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats. 1528 15

Most gut peptides exert their effects through G protein-coupled receptors, a family of about 700 membrane proteins, 87 of which are presently known to have peptide ligands. Three additional gut peptide receptors are not G protein-coupled receptors but regulate intracellular cyclic GMP accumulation. The aim of this review is to illustrate how the sequencing of the human genome and other recent advances in genomics has contributed to our understanding of the role of peptides and their receptors in gastrointestinal function. Recent discoveries include the identification of receptors for the peptides motilin and neuromedin U, and new physiological ligands for the PTH2 receptor, the CRF(2) receptor and the growth hormone secretagogue receptor. Knockout mice lacking specific peptide receptors or their ligands provide informative animal models in which to determine the functions of the numerous peptide-receptor systems in the gut and to predict which of them may be the most fruitful for drug development. Some peptide-receptor signalling systems may be more important in disease states than they are in normal physiology. For example, substance P, galanin, bradykinin and opioids play important roles in visceral pain and inflammation. Other peptides may have developmental roles: for example, disruption of endothelin-3 signalling prevents the normal development of the enteric nervous system and contributes to the pathogenesis of Hirschsprung disease.
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PMID:Clinical endocrinology and metabolism. Receptors for gut peptides. 1553 70

Chronic pain conditions such as rheumatoid arthritis and fibromyalgia are associated with profound hypothalamo-pituitary-adrenal (HPA) axis dysfunction which may exacerbate symptoms of chronic pain. HPA axis dysfunction has also been well documented in animal models of chronic inflammatory pain. However, the role of the HPA axis in animal models of neuropathic pain is currently unknown. Rats with a chronic constriction injury (CCI) of the sciatic nerve that developed marked mechanical allodynia and hyperalgesia of the injured hindpaw were used to determine basal and stimulatory levels of HPA axis activity. Plasma ACTH and corticosterone levels were increased significantly (P < 0.05) in CCI rats after 20 min restraint stress compared with baseline; however, the magnitude of the increase was no different from sham rats. Furthermore, the temporal profile of ACTH release over the 60 min period after termination of restraint was similar between CCI and sham rats suggesting normal glucocorticoid-mediated feedback. Restraint stress also significantly increased (P < 0.05) expression of the immediate early genes c-Fos and FosB within the hypothalamic PVN to a similar extent in CCI and sham rats. Within the parvocellular PVN basal expression of both CRF and AVP mRNA was no different between CCI and sham rats; restraint stress induced a significant 2.5 fold increase (P < 0.05) in CRF mRNA expression in sham rats only. These results suggest that, in contrast to inflammatory immune-mediated pain models where HPA axis function is profoundly altered, in the CCI model of neuropathic pain, basal HPA axis function is unchanged. Furthermore, the HPA axis responds normally to a novel stressor in the face of ongoing nociceptive input, a stimulus known to activate the HPA axis.
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PMID:Normal hypothalamo-pituitary-adrenal axis function in a rat model of peripheral neuropathic pain. 1588 20

We investigated the effects of peripheral injection of sauvagine, a CRF2>CRF1 receptor (corticotropin-releasing factor) agonist compared with CRF, on two sets of tonic colorectal distension (CRDs 30, 40, 50 mmHg, 3-min on/off)-induced visceromotor response (VMR) measured as area under the curve (AUC) of abdominal muscle contraction in conscious female rats. Sauvagine (10 or 20 microg/kg, s.c.) abolished the 226.7+/-64.3% and 90.4+/-38.1% increase in AUC to the 2nd CRD compared with the 1st CRD (performed 30 min before) in female Fisher and Sprague-Dawley (SD) rats, respectively. CRF had no effect while the CRF1 antagonist, antalarmin (20 mg/kg, s.c.), alone or with sauvagine, blocked the enhanced response to the 2nd CRD, performed 60 min after the 1st CRD, and reduced further the AUC by 33.5+/-23.3% and 63.5+/-7.2%, respectively in Fisher rats. These data suggest that peripheral CRF2 receptor activation exerts antinociceptive effects on CRD-induced visceral pain, whereas CRF1 contributes to visceral sensitization.
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PMID:Peripheral injection of sauvagine prevents repeated colorectal distension-induced visceral pain in female rats. 1594 37

In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. The aims of this study were 1) to determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity as well as on other measures of stress sensitivity of the adult animal; and 2) to determine the role of corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF(1)R) in mediating visceral hypersensitivity. Three groups of male Long-Evans rat pups were used: separation from their dam for 180 min daily from postnatal days 2-14 (MS180), daily separation (handling) for 15 min (H), or no handling. The visceromotor responses (VMR) to colorectal distension, stress-induced colonic motility, and anxiety-like behavior were assessed in the adult rats. The VMR was assessed at baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h poststress. Astressin B, a nonselective CRF-R antagonist, or CP-154,526, a selective CRF(1)R antagonist, was administered before the stressor and/or before the 24-h measurement. MS rats developed acute and delayed stress-induced visceral hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited enhanced stress-induced colonic motility and increased anxiety-like behavior. In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF(1)R system.
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PMID:Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats. 1599 24

The effects of corticoliberin fragment CRF(4-6) (Pro-Pro-Ile) on pain sensitivity of rats in "hot plate" test were investigated. Intracerebroventricular administration of tripeptide CRF(4-6) (6, 30, 150 nmol/head) induced dose-dependent antinociception: the latency of paw lick response increased by 7.4 +/- 1.4, 10.1 +/- 1.5 and 16.7 +/- 4.2 s respectively from the basic level of 10.2 +/- 0.9 s. Duration of tripeptide antinociceptive action was 30 min (for 6 nmol) and 60 min (for 30 and 150 nmol). Pretreatment with corticotropin-releasing factor antagonist alpha-helical CRF(9-41) (6.5 nmol/head) 60 minutes before tripeptide administration completely abolished the antinociceptive effects of CRF(4-6) (6 nmol). Therefore corticoliberin receptors seem to be involved in realization of tripeptide influence on pain sensitivity. The data obtained suggest that CRF(4-6) can either directly interact with corticoliberin receptors or modulate activity of CRF-ergic neurons.
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PMID:[Effect of corticoliberin fragment CRF(4-6) on pain sensitivity in rats]. 1635 80


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