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

The specific mechanisms by which nervous system injury becomes a chronic pain state remain undetermined. Historically, it has been believed that injuries proximal or distal to the dorsal root ganglion (DRG) produce distinct pathologies that manifest in different severity of symptoms. This study investigated the role of injury site relative to the DRG in (1) eliciting behavioral responses, (2) inducing spinal neuroimmune activation, and (3) responding to pharmacologic interventions. Rats received either an L5 spinal nerve transection distal to the DRG or an L5 nerve root injury proximal to the DRG. Comparative studies assessed behavioral nociceptive responses, spinal cytokine mRNA and protein expression, and glial activation after injury. In separate studies, intrathecal pharmacologic interventions by using selective cytokine antagonists (interleukin-1 [IL-1] receptor antagonist and soluble tumor necrosis factor [TNF] receptor) and a global immunosuppressant (leflunomide) were performed to determine their relative effectiveness in these injury paradigms. Behavioral responses assessed by mechanical allodynia and thermal hyperalgesia were almost identical in the two models of persistent pain, suggesting that behavioral testing may not be a sensitive measure of injury. Spinal IL-1beta, IL-6, IL-10, and TNF mRNA and IL-6 protein were significantly elevated in both injuries. The overall magnitude of expression and temporal patterns were similar in both models of injury. The degree of microglial and astrocytic activation in the L5 spinal cord was also similar for both injuries. In contrast, the pharmacologic treatments were more effective in alleviating mechanical allodynia for peripheral nerve injury than nerve root injury, suggesting that nerve root injury elicits a more robust, centrally mediated response than peripheral nerve injury. Overall, these data implicate alternate nociceptive mechanisms in these anatomically different injuries that are not distinguished by behavioral testing or the neuroimmune markers used in this study.
 ...
PMID:Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment. 1159 43

Fatigue is prominent in cancer patients and probably multifactorial in origin. Factors contributing to fatigue include anemia, weight loss, fever, pain, medication, and infection. In cancer patients, many of these factors are influenced by a frequently disrupted balance between endogenous cytokine levels and their natural antagonists. Indeed, cancer cells and the immune system appear to overexpress a range of cytokines in patients with malignancies. Some of these cytokines act as autocrine or paracrine growth factors for the neoplastic tissue while simultaneously causing secondary symptoms related to fatigue. For instance, cancer-associated anemia may be due to a blunted erythropoietin response and/or cytokines (interleukin-1 [IL-1], IL-6, tumor necrosis factor-alpha [TNF-alpha]), which suppress erythropoiesis. Cancerous cachexia, a wasting syndrome and a hallmark of cancer, can be attributed to loss of appetite or enhanced energy expenditure. Several different interleukins, as well as TNF, interferon-gamma, and leukemia inhibitory factor, act as cachectins in animal models. Similarly, fever and night sweats are influenced by pyrogenic cytokines. Recently, molecules that function as cytokine antagonists have been identified. These molecules may be exploitable in combating the components of cancer-related fatigue, and may inhibit tumor growth as well.
 ...
PMID:The role of cytokines in cancer-related fatigue. 1159 87

The aim of this study was to verify the role played by mononuclear cells in an acute (nonimmune) inflammatory reaction. Mononuclear cells purified from rat peripheral blood were incubated for 1, 2, or 24 h with 100 or 250 microg/ml carrageenin (Cg). The resultant donor supernatant was injected into recipient rats to test its ability to induce hyperalgesia (reduction in threshold for paw pressure) and edema (increase in paw volume). Mononuclear cell supernatants (MnS) induced a significant time- and dose-dependent hyperalgesia and edema in rat paws, which reached a maximal effect at 3 h, lasted for 6 h, and returned to basal levels at 24 h of injection. Prostaglandins and cytokines (interleukin 1, 2, 6, 8, and tumor necrosis factor alpha) accounted for the hyperalgesia induced by MnS, as it was reduced (40 to 90%) by synthesis inhibitors such as indomethacin, dexamethasone, rolipram, and cyclosporin added to the cultures at a microgram dose-range. Edema was dependent on serotonin release in rat paws. These results indicate that mononuclear cells may be important contributors to acute inflammatory reactions, especially under those conditions where pain is an important component.
 ...
PMID:Hyperalgesia and edema responses induced by rat peripheral blood mononuclear cells incubated with carrageenin. 1182 Apr 54

Rheumatoid arthritis (RA) is a systemic inflammatory disease with polyarticular synovitis leading to formation of rheumatoid pannus and subsequent erosion of articular cartilage and bone. Prostaglandins (PGs)--a group of arachidonic acid metabolites found at elevated levels in synovial fluid and synovial membrane are considered to play a pivotal role in development of vasodilatation, fluid extravasation and pain in synovial tissues. Moreover, there is increasing evidence that PGs (especially prostaglandin E2) are mediators involved in complex interactions leading to development of erosions of articular cartilage and juxta-articular bone. Cyclooxygenase is an enzyme playing crucial role in PGs production. It is known that two forms of cyclooxygenase exist: cyclooxygenase-1 (COX-1) playing house-keeping functions and cyclooxygenase-2 (COX-2) involved in inflammatory responses. Synovial tissues from patients with RA are shown to contain COX-2 and to a less extent COX-1. COX-2 expression in rheumatoid synovium is induced by proinflammatory cytokines, mainly IL-1, while corticosteroids are capable of inhibiting COX-2 expression. The understanding of crucial role of COX-2 in synovial inflammation led to development of new group of anti-inflammatory agents--selective COX-2 inhibitors, that inhibit specifically COX-2, providing effective anti-inflammatory action without the side effects associated with inhibition of COX-1. In the context of widespread use of selective COX-2 inhibitors hypothetical role of COX-1 in RA pathology should be elucidated.
 ...
PMID:[The role of cyclooxygenase and prostaglandins in the pathogenesis of rheumatoid arthritis]. 1185 19

When tissue is destroyed, pain arises. Tissue destruction as well as wound healing are associated with an inflammatory reaction. This leads to activation of nociceptors ("pain receptors") which can cross-communicate with the inflammatory infiltrate. The following review will concentrate on pain-exaggerating (hyperalgesic) and pain-ameliorating (analgesic) mediators which arise from immune cells or the circulation during the inflammation. In the early stages of inflammation endogenous hyperalgesic mediators are produced, including the proinflammatory cytokines IL-1, IL-6 and TNF-alpha, nerve growth factor as well as bradykinin and prostaglandins. Simultaneously, analgesic mechanisms are activated. Opioid peptides such as endorphins, enkephalins and dynorphins are produced by immune cells and can be released locally in the inflamed tissue on stimulation with IL-1 or corticotropin releasing factor. Analgesia is elicited by binding of the opioid peptides to receptors on peripheral sensory neurons. During the course of an inflammatory process, peripheral opioid-mediated analgesia increases. In parallel, antiinflammatory cytokines such as IL-4, IL-10, IL-13 and IL-1ra are produced and reduce hyperalgesic effects of the proinflammatory cytokines initially produced. Inflammatory pain, therefore, is the result of an interplay between hyperalgesic and analgesic mediators. Drugs such as immunosuppressants influencing this interplay may also impair endogenous hyperalgesic and analgesic mechanisms.
 ...
PMID:[Pain and the immune system: friend or foe?]. 1212 5

We report a 62-year old woman with orbital myositis who had a favorable response to intravenous immunoglobulin (i.v.-IG) administration in preventing disease recurrence. She had been suffering from frequent relapses of swelling and redness of the left eye with increasing pain and diplopia caused by restricted eye movement of the left eyeball. T2-weighted magnetic resonance image of the orbit showed enlargement of the left medial rectus muscle. She was treated with 1 g of methylprednisolone per day for 3 days. One mg/kg per day of oral prednisolone was subsequently started with non-steroid anti-inflammatory drugs, which resulted in improvement. However, her symptoms were aggravated while the drug was tapered off even though she used a high dose of oral prednisolone. High dose of i.v.-IG (400 mg/kg per day) was then administered for five days. Since the treatment, she has been free from recurrences of the disease for over one year, suggesting that i.v.-IG can prevent the recurrence of orbital myositis. Some reports have suggested that i.v.-IG treatment is useful to prevent recurrence of other forms of inflammatory myositis, such as dermatomyositis or polymositis. Overproduction of the pro-inflammatory cytokines (IL-1, IL-1 beta, INF-alpha) and Th1 cytokines (INF-gamma, IL-2) are related to the deterioration of these diseases. I.v.-IG treatment suppresses the production of the pro-inflammatory cytokines. In our case, serum levels of the pro-inflammatory cytokines were all normal, but the IL-4 level was elevated after the i.v.-IG treatment, suggesting that orbital myositis was probably related to the Th1 dominant disease that was suppressed by IL-4.
 ...
PMID:[A patient of recurrent orbital myositis with good response to high-dose intravenous immunoglobulin (i.v.-i.g.) therapy]. 1242 67

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.
 ...
PMID:Cytokines and peripheral analgesia. 1261 63

When pain becomes chronic this is a process that takes place at several levels of the peripheral and central nervous systems. In recent years, proinflammatory substances like bradykinin, prostaglandins and signal molecules like cytokines have been identified as allogenic factors. In the present paper we examined whether cytokines play a role also in non-inflammatory peripheral nerve lesions, i.e. whether they are of importance in the causation of pain in general and whether their antagonists can be used therapeutically. The development of pain after peripheral nerve lesion in animal models follows the process of Wallerian degeneration. During Wallerian degeneration the expression of proinflammatory cytokines in the nerve is upregulated. Here we studied the temporal course of cytokine expression with several different analytical methods, analyzing tumor necrosis factor-alpha (TNF) and interleukin-beta (IL-beta) in the mouse model of chronic constrictive injury (CCI) of the sciatic nerve. This model is associated with reproducible pain related behavior in the animals. We found an early increase of TNF 12 hours after injury. Neutralizing antibodies to TNF were able to reduce the hyperalgesia that evolved due to the nerve injury. As TNF exerts its effects via two receptors, TNF receptor 1 (TNF-R1) and TNF receptor 2 (TNF R2), we also investigated, which of the receptors is relevant to the causation of pain in this model. It turned out that antibodies to TNF-R1, but not to TNF-R2 reduced hyperalgesia, indicating that TNF-R1 is the receptor concerned. Neutralizing antibodies to IL-1 receptor and to IL-6 receptor also reduced pain related behavior. These results lead to the conclusion that proinflammatory cytokines are involved not only in inflammatory pain but also in neuropathic pain. Therapeutic strategies involving cytokine inhibition have been tested experimentally and are already being used in preliminary clinical studies in immune-mediated diseases. In the future, they might be a useful addition to the range of treatments for patients with neuropathic pain.
 ...
PMID:[Animal studies on neuropathic pain: the role of cytokines and cytokine receptors in pathogenesis and therapy]. 1279 19

Cancer anorexia-cachexia syndrome (CACS) is a combination of anorexia, tissue wasting, weight loss and poor performance status. Some CACS symptoms are due to a macrophage production of TNF and IL-1, while the metabolic effects are mainly explained by the release of IL-6 from tumor cells. Clinical treatment of CACS involves progestational agents (medroxyprogesterone acetate, MPA, megestrol acetate, MA) for long term treatment. The use of prokinetic agents (like metoclopramide) is recommended, especially if patients need concomitant opioid treatment for pain; if otherwise indicated, corticosteroids are useful for short periods. The administration of artificial nutrition should be individualized following the clinical condition of the patient and possibly taking into account the wishes of the patient. The practical evaluation criteria of the drugs employed for CACS are based on weight increase and appetite stimulation. Hence, a new approach to the mechanism of action of MPA, MA and of other agents is urgently needed.
 ...
PMID:Treatment of the cancer anorexia-cachexia syndrome: a critical reappraisal. 1286 46

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.
Curr Pain Headache Rep 2003 Oct
PMID:Fibromyalgia, hepatitis C infection, and the cytokine connection. 1294 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>