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)

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma levels of tumor necrosis factor and endothelial response in patients with chronic arterial obstructive disease or Raynaud's phenomenon. 798 28

Tumor necrosis factor alpha (TNF-alpha) is known to induce wasting in humans and animals. This study was undertaken to determine TNF-alpha concentrations in children with sickle cell disease (SCD) and whether high TNF-alpha levels are more likely to be present in children with growth deficits, infection, or pain crisis. Tumor necrosis factor alpha was measured using enzyme immunoassay in 143 blood samples obtained from 101 children. Mean TNF-alpha levels were higher in patients (50 pg/mL) than in 21 control children (19 pg/mL) and in 26 laboratory employees (20 pg/mL). During the follow-up period, 35%, 38%, and 28% of children with SCD had infection, pain crisis, or a blood transfusion, respectively. Mean TNF-alpha concentrations were higher in children who had an infection than in those who did not. No significant effect of pain crisis or blood transfusion was observed. Tumor necrosis factor alpha concentrations were above normal (> 40 pg/mL) in 15% of controls, 34% of children with SCD, and 52% of children with SCD who had an infection and 33% of those who did not. A higher percentage of children who had elevated TNF-alpha levels had weight (46% versus 31%) or height (50% versus 28.6%) deficits than children who had normal TNF-alpha levels. These results indicate that most children with SCD in stable condition have normal TNF-alpha concentrations and that those with high TNF-alpha levels are more likely to have growth deficits.
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PMID:Tumor necrosis factor alpha in children with sickle cell disease in stable condition. 954 73

Tumor necrosis factor alpha (TNF) may be involved in the pathogenic mechanisms of neuropathic pain by affecting endothelial cells and by upregulation of receptor sensitivity in afferent nerve fibers. To test the hypothesis that TNF plays a role in the vascular changes and the pain-related behavior in an experimental painful neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve, we investigated the effect of thalidomide, a selective blocker of TNF-production in activated macrophages. In rats in which treatment with thalidomide was started preoperatively, there was diminished mechanical allodynia and thermal hyperalgesia during the early stage of the disease. TNF immunohistochemistry revealed reduced endoneurial immunoreactivity on day 5 post surgery as compared to sham-treated animals. The pathologic vascular changes were also reduced in thalidomide-treated rats. Starting treatment with thalidomide at a time point when hyperalgesia was already present did not alter the course of the pain-related behavior. We conclude that preemptive treatment with a substance that blocks production of TNF reduces pain-related symptoms and pathologic vascular changes in the chronic constriction injury model of neuropathic pain.
Pain 1998 Jan
PMID:The effect of thalidomide treatment on vascular pathology and hyperalgesia caused by chronic constriction injury of rat nerve. 951 64

Tumor necrosis factor alpha (TNF) is a potent pro-inflammatory cytokine that produces pain and hyperalgesia following injection. Its algesic effects are due to sensitizing actions on nociceptive primary afferents and to the upregulation of other pro-inflammatory and algesic proteins. In anesthetized rats, we investigated the effect of subcutaneously injected TNF on background activity and mechanical sensitivity of C nociceptors of the sural nerve, as well as its effects on cutaneous plasma extravasation. TNF sensitized C nociceptors dose-dependently; the optimal dose (5 ng) lowered threshold in 66.7% of the tested fibers. This sensitization occurred within 30 min and could last for 2 or more hours. Injected TNF had no effect on Abeta mechanoreceptive fibers. In addition, TNF evoked ongoing activity in 14% of C nociceptors and caused significant and dose-related increases in vascular permeability in glabrous skin. Our data suggest that TNF released during disease or after tissue injury participates in the generation of hyperalgesia and inflammation.
Pain 2000 Mar
PMID:Nociceptive and inflammatory effects of subcutaneous TNFalpha. 1069 13

Tumor necrosis factor alpha (TNF-alpha) may have a pivotal role in the genesis of mechanical inflammatory hyperalgesia in rats and in the nociceptive writhing response in mice. Thalidomide has been shown to selectively inhibit TNF-alpha production. We therefore investigated the effect of thalidomide on these responses as well as on the hot plate response in mice. Hyperalgesic responses to intraplantar (i.pl.) injections of carrageenin or bradykinin, which act by stimulating TNF-alpha release, but not responses to TNF-alpha or prostaglandin E(2), were inhibited in a dose-dependent manner by pretreatment of the animals with thalidomide. The nociceptive writhing responses induced by intraperitoneal (i.p.) injections of zymosan or acetic acid were also inhibited in a dose-dependent manner by pretreatment of mice with thalidomide. Moreover, the thalidomide pretreatment also reduced the TNF-alpha mRNA levels in the peritoneal cells induced by injection of zymosan in mice. The analgesic effect of thalidomide is not due to a central effect, since the drug had no effect in the hot plate test. The demonstration that thalidomide is able to inhibit inflammatory hyperalgesia in rats and the writhing nociceptive response in mice suggests that these analgesic effects seem to be a consequence of the inhibition of TNF-alpha production, and indicates the need for investigations on the possibility of the use of thalidomide for the treatment of pain refractory to classical non-narcotic analgesics.
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PMID:Analgesic effect of thalidomide on inflammatory pain. 1072 Jun 40

Tumor necrosis factor alpha (TNF) injected into the sciatic nerve and neutralizing antibodies to its receptor injected around the nerve are respectively associated with inducing and blocking pain behavior beginning 1 to 3 days post-injection. This study examined the acute effects of TNF applied around the nerve trunk on the mechanical threshold (determined with von Frey hairs) and withdrawal latency to radiant heat. TNF (0.9 and 7.7 ng in 90 microL) injected onto the nerve via an indwelling catheter elicited a decrease in mechanical threshold. Following the low dose of TNF, no change in thermal latency was observed; after the 7.7 ng dose, thermal thresholds decreased and returned to baseline multiple times within the 3-hour observation period. Identical doses of TNF injected near, but not on the nerve, 90 ng of TNF injected on the nerve, and vehicle were without effect on either modality. These data indicate that effects of acutely administered TNF to the nerve trunk are capable of producing modality specific pain behavior. These changes may represent a first step in TNF-induced neuropathic pain.
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PMID:Epineurial application of TNF elicits an acute mechanical hyperalgesia in the awake rat. 1090 68

Inflammation in the subacromial bursa causes pain in patients suffering from rotator cuff tear, with this long-lasting inflammation leading to fibrosis and thickening of the subacromial bursa. Both inflammatory cytokines and mechanical stress, and impingement in the subacromial space, might induce and worsen this inflammation. However, little is known of the mechanism of this inflammation. In this study, we used immunohistological staining to demonstrate the expression of Interleukin-1 beta (IL-1 beta), Tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), and basic fibroblast growth factor (bFGF) in subacromial bursa derived from the patients suffering from rotator cuff tear. On the other hand the expression of these inflammatory cytokines and growth factors were little detected only to a small degree in patients with anterior shoulder instability who did not have severe shoulder pain and impingement in the subacromial space. Our findings suggest that those inflammatory cytokines and growth factors may play an important role in inflammation of the subacromial bursa. Controlling the expression of these cytokines and growth factors might be important for treating patients suffering from shoulder pain due to rotator cuff tear.
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PMID:Immunolocalization of cytokines and growth factors in subacromial bursa of rotator cuff tear patients. 1156 92

Tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) are pro-inflammatory cytokines capable of altering the sensitivity of sensory neurons. Because sensitization elicited by IL-1beta and TNFalpha is blocked by inhibition of the inducible enzyme, cyclooxygenase-II (COX-2), we examined whether these cytokines could increase COX-2 expression in dorsal root ganglion (DRG) cultures. Treatment of cell cultures with either IL-1beta or TNFalpha increases immunoreactive COX-2, as measured by immunoblotting, in a time- and concentration-dependent manner. A 24-h pretreatment with 10 ng/ml IL-1beta or 50 ng/ml TNFalpha augmented COX-2 expression 50- and 8-fold over basal levels, respectively. Immunohistochemistry established the presence of COX-2-like immunoreactivity in both neuronal and non-neuronal cells in culture. The addition of IL-1 receptor antagonist blocked the induction of COX-2 expression by IL-1beta, but did not alter TNFalpha-stimulated increases in COX-2, indicating that the mechanism of TNFalpha is not limited to increasing the expression of IL-1beta. The basal and TNFalpha-induced expression of COX-2 was not dependent on the presence of NGF in the growth media. IL-1beta and TNFalpha treatment for 24 h enhanced prostaglandin E2 (PGE2) production 2-4-fold, which was blocked by pretreatment with the COX-2 inhibitor, NS-398. Exposing cultures to PGE2, IL-1beta, or TNFalpha for 24 h did not alter PGE2 receptor (EP) mRNA levels. These results indicate that TNFalpha and IL-1beta induce the functional expression of COX-2 but not EP receptors in DRG cells in culture and suggest that cytokine-induced sensitization of sensory neurons is secondary to prostaglandin production and not alterations in EP receptors.
Pain 2005 Jan
PMID:Tumor necrosis factor alpha and interleukin-1beta stimulate the expression of cyclooxygenase II but do not alter prostaglandin E2 receptor mRNA levels in cultured dorsal root ganglia cells. 1562 71

Tumor necrosis factor alpha (TNF-alpha) is implicated in the development of persistent pain. Its expression increases both spinally and supraspinally after peripheral inflammation. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Prefrontal synaptic transmission is potentiated in mice with chronic pain through an enhancement of presynaptic transmitter release. However, it is not known if TNF-alpha expression is altered in the ACC in response to persistent pain and if synaptic transmission within this region is modulated by TNF-alpha. In the present study, we examined TNF-alpha expression in the mouse ACC following hind-paw administration of complete Freund's adjuvant (CFA) and examined the role of TNF-alpha in ACC synaptic transmission. Quantification of TNF-alpha at the protein level (by ELISA) revealed enhanced expression following CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that TNF-alpha significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC. Our findings provide evidence that presynaptic alterations caused by peripheral inflammation is partly attributable to the up-regulation of TNF-alpha in the ACC.
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PMID:TNF-alpha involves in altered prefrontal synaptic transmission in mice with persistent inflammatory pain. 1722 72

Recently, we reported the dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) activity by some phenylsulphonyl urenyl chalcone derivatives. 2,4-dichloro-4'N[N'(4''methylphenylsulphonyl)urenyl] chalcone (Me-UCH9), was selected in the present study to determine its potential anti-inflammatory and analgesic effect after oral administration in several animal models related to the activation of COX-2 and 5-LO pathways. In the zymosan stimulated mouse air pouch model, Me-UCH9, reduced in a dose-dependent manner leukotriene B(4) (LTB(4)) levels in pouch exudates obtained at 4 h, as well as prostaglandin E(2) (PGE(2)) generated through COX-2 activation at 24 h. Tumor necrosis factor alpha (TNF-alpha) and myeloperoxidase activity were also strongly inhibited in this model. Me-UCH9 significantly reduced granuloma size and vascular index determined in the murine air pouch granuloma model of angiogenesis. In the carrageenan-induced paw edema, this compound inhibited inflammatory response and pain, as well as PGE(2) and LTB(4) content in paw edematous fluid. Analgesic properties were corroborated in the murine phenyl-p-benzoquinone-induced writhing test. Finally, Me-UCH9 exerted anti-inflammatory effects in the chronic model of rat adjuvant-induced arthritis, both inhibiting paw swelling and reducing PGE(2) content. Our findings confirm that Me-UCH9 can modulate inflammatory and nociceptive responses in relation to the dual inhibition of COX-2 and 5-LO activities presented by this compound.
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PMID:Evaluation of the anti-inflammatory and analgesic activity of Me-UCH9, a dual cyclooxygenase-2/5-lipoxygenase inhibitor. 1749 Jun 89


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