Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physical exercise is widely used in the treatment of chronic pain patients, and direct measurement of physical capabilities is needed to objectively document change. In this study, 46 residential chronic pain patients undergoing treatment at a multidisciplinary rehabilitation center were administered a cycle ergometer graded exercise test, using a Medical Graphics CAD/NET exercise system, to measure aerobic fitness and other physiological parameters before and after the four-week treatment program. Patients evinced highly statistically significant changes in all major indices of cardiopulmonary functioning, including MAXVO2 and METS, and a measure of lower body power (WATTS). Possible mechanisms underlying such dramatic changes in this short time period include improved physical fitness, learning or desensitization to symptoms associated with exertion, and improved effort. Documenting treatment-related changes is important, and metabolic exercise testing provides an objective method for assessing changes in functional capacities. Such changes may have important practical implications for these individuals. The importance of assessing and improving aerobic fitness in chronic pain populations is discussed.
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PMID:Assessment of aerobic power in chronic pain patients before and after a multi-disciplinary treatment program. 164 22

The new SKY epidural catheter was evaluated, based upon information collected about implant and use of 53 catheters by 51 patients. Catheters were used to treat chronic pain of a malignant (n = 25) and nonmalignant (n = 28) origin. Of 3450 treatment days, 89% occurred at home. Mean catheter use for malignant and nonmalignant conditions were 58.6 and 76.3 days/patient, respectively. Visual analogue pain scores in the first wk after implant indicated 79% of patients achieved good to excellent pain relief. Clinical impressions indicated this group achieved substantial long-term pain relief. No serious complications were observed. Two types of leakage required removing 5 catheters, prompting changes that eliminated subsequent leakages of both types. Accidental patient retraction and subcutaneous infection each required a catheter removal. No subarachnoid or epidural infections occurred. The SKY catheter proved to be safe and reliable. Therapy was cost-effective, since patients achieved substantial pain relief while treated at home.
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PMID:Initial clinical experience with the SKY epidural catheter. 201 55

The possible changes in neutral endopeptidase EC 3.4.24.11 ("enkephalinase", NEP), mu and delta opioid binding sites, were investigated using in vitro quantitative radioautography in various regions of the central nervous system of the Freund's adjuvant-induced arthritic rat, a model of chronic pain. Enkephalinase was labeled by a specific tritiated inhibitor, [3H]N-[(2RS)-3-hydroxyaminocarbonyl-2-benzyl-1-oxopropyl]glycine ([3H]HACBO-Gly), while mu and delta opioid binding sites were selectively labelled with [3H]Tyr-D-Ala-Gly-(Me)Phe-Gly-ol ([3H]DAGO) and [3H]Tyr-D-Thr-Gly-Phe-Leu-Thr ([3H]DTLFT), respectively. As compared to controls, no significant modifications were found in NEP, mu or delta binding sites at both supraspinal and spinal levels of arthritic rats. These results suggest that the enhanced efficiency of exogenous opioids or endogenous enkephalins, reported to occur in this model of chronic inflammatory pain, are not directly related to changes in mu and delta opioid binding sites or steady state levels of NEP.
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PMID:Lack of significant changes in mu, delta opioid binding sites and neutral endopeptidase EC 3.4.24.11 in the brain and spinal cord of arthritic rats. 255 47

Twenty knee dislocations in 19 patients (one bilateral) occurred over a period of 20 years. The age range was 21 to 65 years, with an average age of 40.8 years. There were two popliteal artery and eight peroneal nerve injuries in the group. All patients were managed by early closed reduction at the scene of the accident or at the admitting hospital. Treatment consisted of 13 acute arthrotomies with complete ligamentous repair, one partial ligament repair, two delayed repairs, and four cast applications. Both anterior and posterior cruciate ligaments were torn in each knee surgically examined. In contrast to cruciate injuries in nondislocated knees, avulsion of bone of the PCL was present in 14 of 16 and of the ACL in ten of 16. Complete follow-up study including examination and radiographic evaluation was obtained on 18 knees in 17 patients. Special investigations of 13 with acute complete ligament repair, followed from 12 months to 48 months (average of 24 months), showed loss of joint motion following this injury. Clinical instability was generally not a problem, but chronic pain and discomfort were present in 46%. The average knee diagnostic score was 43. Seventy-seven percent of the patients returned to vigorous sports activities. Early operative repair followed by cast bracing and manipulation at three months (if flexion was less than 90 degrees) is recommended in young, active patients.
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PMID:Complete knee dislocation. A follow-up study of operative treatment. 402 70

FMS is a complex condition mainly characterized by the presence of chronic pain. The nature of this complaint thus demands assessment in a hierarchal fashion of the various components of the pain system ranging from the nociceptor through to complex central pain-processing mechanisms. The condition is common and represents the most important defined chronic pain syndrome. Elucidation of the mechanisms and better management of FMS will result in improved knowledge of a whole range of related chronic pain syndromes. The database in FMS is necessarily large but does need to be focused according to the need of the person constructing the database and the need of the individual with FMS. As our understanding of FMS evolves, better ways of assessing the various dimensions of the problem will be devised. Perhaps the challenge we face is to bring all the parts together. In doing so, we may find there is a single essential component that links all the clinical features together, which correlates well with severity, disability and outcome, which is amenable to treatment programs, and which is measurable. The search for the soul of the "elephant" of FMS continues.
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PMID:A database for fibromyalgia. 763 Oct 42

To study the hormonal perturbations in FMS patients we injected sixteen FMS patients and seventeen controls a cocktail of the hypothalamic releasing hormones: Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH), Growth hormone-releasing hormone (GHRH), and Luteinizing hormone-releasing hormone (LHRH) and observed the hormonal secretion pattern of the pituitary together with the hormones of the peripheral endocrine glands. We found in FMS patients elevated basal values of ACTH and cortisol, lowered basal values of insulin-like growth factor I (IGF-I) and of triiodothyronine (T3), elevated basal values of follicle-stimulating hormone (FSH) and lowered basal values of estrogen. Following injection of the four releasing-hormones, we found in FMS patients an augmented response of ACTH, a blunted response of TSH, while the prolactin response was exaggerated. The effects of LHRH stimulation were investigated in six FMS patients and six controls and disclosed a significantly blunted response of LH in FMS. We explain the deviations of hormonal secretion in FMS patients as being caused by chronic stress, which, after being perceived and processed by the central nervous system (CNS), activates hypothalamic CRH neurons. CRH, on the one hand, activates the pituitary-adrenal axis, but also stimulates at the hypothalamic level somatostatin secretion which, in turn, causes inhibition of GH and TSH at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH by its ability to inhibit hypothalamic LHRH release, although it could act also directly on the ovary by inhibiting FSH-stimulated estrogen production. We conclude that the observed pattern of hormonal deviations in FMS patients is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.
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PMID:Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones. 1002 90

A large body of data from a number of different laboratories worldwide has demonstrated a general tendency for reduced adrenocortical responsiveness in CFS. It is still not clear if this is secondary to CNS abnormalities leading to decreased activity of CRH- or AVP-producing hypothalamic neurons. Primary hypofunction of the CRH neurons has been described on the basis of genetic and environmental influences. Other pathways could secondarily influence HPA axis activity, however. For example, serotonergic and noradrenergic input acts to stimulate HPA axis activity. Deficient serotonergic activity in CFS has been suggested by some of the studies as reviewed here. In addition, hypofunction of sympathetic nervous system function has been described and could contribute to abnormalities of central components of the HPA axis. One could interpret the clinical trial of glucocorticoid replacement in patients with CFS as confirmation of adrenal insufficiency if one were convinced of a positive therapeutic effect. If patient symptoms were related to impaired activation of central components of the axis, replacing glucocorticoids would merely exacerbate symptoms caused by enhanced negative feedback. Further study of specific components of the HPA axis should ultimately clarify the reproducible abnormalities associated with a clinical picture of CFS. In contrast to CFS, the results of the different hormonal axes in FMS support the assumption that the distortion of the hormonal pattern observed can be attributed to hyperactivity of CRH neurons. This hyperactivity may be driven and sustained by stress exerted by chronic pain originating in the musculoskeletal system or by an alteration of the CNS mechanism of nociception. The elevated activity of CRH neurons also seems to cause alteration of the set point of other hormonal axes. In addition to its control of the adrenal hormones, CRH stimulates somatostatin secretion at the hypothalamic level, which, in turn, causes inhibition of growth hormone and thyroid-stimulating hormone at the pituitary level. The suppression of gonadal function may also be attributed to elevated CRH because of its ability to inhibit hypothalamic luteinizing hormone-releasing hormone release; however, a remote effect on the ovary by the inhibition of follicle-stimulating hormone-stimulated estrogen production must also be considered. Serotonin (5-HT) precursors such as tryptophan (5-HTP), drugs that release 5-HT, or drugs that act directly on 5-HT receptors stimulate the HPA axis, indicating a stimulatory effect of serotonergic input on HPA axis function. Hyperfunction of the HPA axis could also reflect an elevated serotonergic tonus in the CNS of FMS patients. The authors conclude that the observed pattern of hormonal deviations in patients with FMS is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily evoked by activated CRH neurons.
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PMID:Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome. 1108 55

As demonstrated above, the anatomy and neuropharmacology of the pain pathways within the CNS, even to the level of the midbrain, are extraordinarily complex. Indeed, discussions of the effects of these agents on the neuropharmacology of the thalamus, hypothalamus, and cortex were excluded from this review owing to their adding further to this complexity. Also, the dearth of data regarding FMS pain pathophysiology necessitated a relatively generic analysis of the pain pathways. As mentioned in the introduction, the current thought is that central sensitization plays an important role in FMS. However, we see in this chapter that the behavioral state of central sensitization may be a result of alterations in either the ascending systems or in one or more descending systems. Studies to assess the presence or relative importance of such changes in FMS are difficult to perform in humans, and to date there are no animal models of FMS. Accepting these limitations, it is apparent that many drugs considered to date for the treatment of FMS do target a number of appropriate sites within both the ascending and descending pain pathways. The data regarding clinical efficacy on some good candidate agents, however, is extremely preliminary. For example, it is evident from the present analysis that SNRIs, alpha 2 agonists, and NK1 antagonists may be particularly well suited to FMS, although current data supporting their use is either anecdotal or from open-label trials [114,149]. Other sites within the pain pathways have not yet been targeted. Examples of these include the use of CCKB antagonists to block on-cell activation or of nitric oxide synthetase antagonists to block the downstream mediators of NMDA activation. Efficacy of such agents may give considerable insight into the pathophysiology of FMS. Finally, as indicated previously, FMS consists of more than just chronic pain, and the question of how sleep abnormalities, depression, fatigues, and so forth tie into disordered pain processing is being researched actively. Future research focusing on how the various manifestations of FMS relate to one another undoubtedly will lead to a more rational targeting of drugs in this complex disorder.
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PMID:The neuropharmacology of centrally-acting analgesic medications in fibromyalgia. 1212 16

In order to study the development of the delivery device of long-acting local anaesthetics for post-operative analgesia and control of chronic pain of cancer patient, fentanyl loaded poly(l-lactide-co-glycolide) (PLGA, molecular weight; 5000, 8000, 20,000, and 33,000 g/mole) microspheres (FMS) were studied. FMS were prepared by an emulsion solvent-evaporation method. The influence of several preparation parameters such as initial drug loading, PLGA concentrations, emulsifier concentrations, oil phase volume and mole ratio and molecular weight has been investigated on the fentanyl release patterns. Generally, the drug showed the biphasic release patterns, with an initial diffusion followed by a lag period before the onset of the degradation phase, but there were no lag times in the device. Fentanyl was slowly released from FMS over 10 days in vitro, with a quasi-zero order property. The release rate increased with increasing drug loading as well as increasing polymer concentration with a relatively small initial burst effect. From the results, FMS may be a good formulation to deliver the anaesthesia for the treatment of chronic pain.
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PMID:Study on in vitro release patterns of fentanyl-loaded PLGA microspheres. 1290 42

In the field of neuromuscular diseases, pain and its management remain imperfectly understood and described. We study 68 unselected, consecutive adult patients attending a multidisciplinary consultation for hereditary myopathy. Forty-six (67%) were suffering from chronic pain. Pain was assessed with self report questionnaire and a standardized clinical evaluation. Mean duration of the pain was 7.2+/-8.9 years, and multiple body sites were involved in 91% of cases. Usual pain intensity (Visual Analogue Scale 0-100) was moderate (39.5+/-26.2). For 42 patients (91%) the principal cause of the pain was of muscular origin, with frequent features of myofascial pain syndromes (MPS, 50%) and fibromyalgia (FMS, 26%). Pain was the major complaint for 6.3% of the patients. Pain management was essentially based on physiotherapy. Only a minority of patients (38%) has an appropriate drug treatment. Common analgesics appeared to be very effective in these patients.
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PMID:Clinical study of chronic pain in hereditary myopathies. 1469 Jun 75


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