Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of patients suffering from chronic neuropathic pain remains a clinical challenge, particularly in cases where opioid therapy fails to provide sufficient pain relief. Spinal sensitization might be one cause for induction and maintenance of such states of pain, frequently accompainied by symptoms like allodynia, hyperalgesia and temporal summation of second pain. Experimental data concerning the role of NMDA-mediated processes in central sensitization and the effects of NMDA receptor antagonists in different models of neuropathic pain are reviewed. In clinical trials ketamine and other NMDA receptor blocking agents caused a significant reduction of hypersensitive states of pain, but nearly all authors described psychomimetic and other side effects. Aminoadamantanes like memantine and amantadine also have NMDA blocking properties and are widely used in the treatment of Parkinson's disease. Further clinical studies may reveal whether these substances will play a role as adjuncts in future pain treatment. Improving the efficacy of opioids by blocking NMDA receptor-mediated activity constitutes another clinically relevant concept for pain management. Numerous experiments have shown synergistic effects of NMDA antagonists and opioids in analgesia, while the development of opioid tolerance was prevented.
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PMID:[NMDA-receptor antagonist in pain therapy]. 974 42

Neck pain in the suboccipital and paracervical region ('coathanger' configuration) is often reported by patients with autonomic failure and orthostatic hypotension. The frequency of this pain, along with pains in the buttock and calf regions, was determined by questionnaire in two major groups with primary chronic autonomic failure--pure autonomic failure (PAF) and multiple system atrophy (MSA). Comparisons were made with Parkinson's disease, cerebellar degeneration and other disorders in which neurological symptoms overlap but in which there was neither autonomic failure nor orthostatic hypotension. Neck pain was present in 93% of patients with PAF, 51% of patients with MSA and 38-47% of the non-autonomic groups. Buttock pain was present in smaller but similar proportions (8-19%) of each group, like calf pain (23-37%). Neck pain in PAF and MSA differed from that in the other groups in being relieved by sitting or lying flat and in being associated with factors that lower blood pressure in these patients. Buttock pain was posturally related in PAF and MSA; for calf pain there was no difference between groups. Neck pain was related to the degree of orthostatic hypotension; in PAF patients, whose postural blood-pressure fall was greater than that in MSA, there was a greater frequency of neck pain.
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PMID:Neck and other muscle pains in autonomic failure: their association with orthostatic hypotension. 977 93

Ovarian steroids produce a variety of effects on the brain, influencing diverse nonreproductive processes such as cognitive function, motor activity, seizure susceptibility, and pain sensitivity, as well as pathological processes such as Parkinson's disease and Alzheimer's disease. Studies of ovarian hormone effects on animal brains have revealed a wide array of neurochemical and structural effects of ovarian steroids, which are reviewed in this article. These studies provide a foundation for understanding hormone effects on mood, behavior, and cognition in the menstrual cycle, during reproductive transitions and in depressive illness.
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PMID:Clinically relevant basic science studies of gender differences and sex hormone effects. 980 50

Sleep disorders are common and well documented in patients with Parkinson's disease (PD). However, most data on sleep in patients with PD are derived from selected patient populations. This community-based survey evaluated the prevalence of and risk factors for sleep disturbances in an unselected group of 245 patients with PD and two control groups of similar age and sex distribution: 100 patients with another chronic disease (diabetes mellitus) and 100 healthy elderly persons. Nearly two thirds of the patients with PD reported sleep disorders, significantly more than among patients with diabetes (46%) and healthy control subjects (33%). About a third of the patients with PD rated their overall nighttime problem as moderate to severe. The most common sleep disorders reported by the patients with PD were frequent awakening (sleep fragmentation) and early awakening. Sleep initiation showed no significant difference compared with the control groups. Pain and cramps were not more prevalent among the patients with PD, but they were more likely to report sleep disturbed by myoclonic jerks. Use of sedatives was common in all three groups but significantly higher in the PD group than in the healthy elderly. Symptoms of depression and duration of levodopa treatment showed a significant correlation with sleep disorders in the PD group. This community-based study confirms that sleep disorders are common and distressing in patients with PD. The strong correlation between depression and sleep disorders in patients with PD underlines the importance of identifying and treating both conditions in these patients.
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PMID:A community-based study of sleep disorders in patients with Parkinson's disease. 982 12

A series of conformationally restricted analogues of nicotine has been synthesized and evaluated as agonists of neuronal acetylcholine receptors. Compound 2 (SIB-1663), which selectively activated human recombinant alpha 2 beta 4 and alpha 4 beta 4 nAChRs, was shown to be active in animal models of Parkinson's disease and pain.
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PMID:Conformationally restricted analogues of nicotine and anabasine. 987 8

Although the application of stereotactic radiosurgery for the management of functional brain disorders began in 1951, almost 50 years elapsed before it received appropriate attention. Radiosurgical techniques are used to create image-guided, physiological inactivity or focally destructive brain lesions without neurophysiological guidance. The lack of neurophysiological guidance remains the greatest argument against the use of radiosurgery for selected disorders. Current anatomic targets include the trigeminal nerve (for trigeminal neuralgia), the thalamus (for tremor or pain), the cingulate gyrus or anterior internal capsule (for pain or psychiatric illness), the globus pallidus (for symptoms of Parkinson's disease), and the hippocampus (for epilepsy). The use of radiosurgery as a "lesion generator" is based on extensive animal studies that defined the dose, volume, and temporal response of the irradiated tissue. The usefulness of radiosurgery has been compared with that of microsurgical, percutaneous, and electrode-based techniques used for functional neurological disorders. At present, the long-term results after functional radiosurgery procedures remain to be documented. The current indications and expected outcomes after radiosurgery are discussed.
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PMID:Functional radiosurgery. 989 59

The use of animal cells, tissues, or organs for humans is being investigated as an alternative to allotransplantation and as therapy for a broad range of disease states including diabetes, Parkinson's disease, and neurologic pain control. The risk of transmitting novel infections with these tissues, xenozoonoses, has led to much debate. It is well recognized that infections are a hazard with the use of all biologic agents. In addition, infections from human donors remain a major cause of morbidity and mortality after allotransplantation. Accordingly the potential for animal microbial agents to be pathogenic in the human recipient after xenotransplantation and be transmissible to others must be critically examined. Along with laboratory-based research, clinical trials must be conducted in a manner to evaluate the transmission of potential animal infections. Pretransplant evaluation should include discussions with the candidate and, if possible, with close contacts. Information must be provided as to the potential risks of infection and transmission to others. Behavioral modifications which can decrease spread of infections should be emphasized. Serial samples should be obtained from the patients at defined intervals and if recipients become ill. In addition, archiving samples for future evaluation is critical. Prospective evaluation will enhance the ability to define and understand the spectrum of xenogeneic infections.
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PMID:Xenozoonoses and the xenotransplant recipient. 992 10

Patients with fibromyalgia sometimes have sign of a movement disorder in addition to sensory disturbances sometimes similar as those found in akinetic syndromes. Akinesia is due to disturbances in the functions of the cortico-thalamo-nigro-striatal system and associated areas. The reason of this dysfunction in Parkinson's disease is a decreased nigral dopaminergic efferent innervation due to a neuronal degeneration in the pars compacta of the substantia nigra. Changes in other neurotransmitters, like GABA or serotonin, and in receptors and second messengers also occur, with additional modulation due to therapy. The aetiology of nigral malfunction is in only rarely known. Drugs and mutations of some genes are examples which give much insight in the pathogenesis of movement disorders in general. In other akinetic disorders, like multisystem atrophy, corticobasal ganglionic degeneration, and progressive supranuclear palsy, more complex patterns of degeneration have been found. This pathological anatomical disturbances have typical clinical effects which can be studied physiologically and with imaging in vivo. Since basal ganglia play also a role in pain, a comparative study of their involvement in movement disorders and nociception seems to be fruitful, especially in devising new therapeutic strategies.
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PMID:Pathophysiology of akinetic movement disorders: a paradigm for studies in fibromyalgia? 1002 78

This article examines depression in 6 medical conditions: coronary artery disease (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease, pain, and the sex hormone changes of aging. Research is beginning to define specific biological and psychological mechanisms underlying the adverse interactions between depression and these medical conditions. Antidepressant medications, psychosocial therapies, and hormonal manipulations are effective in reducing depressive symptoms. Specific psychosocial interventions may increase longevity in CAD and cancer and may enhance quality of life in HIV infection. Newer antidepressants appear to be safer and better tolerated than older agents for medically ill patients, but do not appear to be as effective for neuropathic pain. Dopamine agonists may benefit depression associated with Parkinson's disease. Hormone replacement therapy may improve subsyndromal depressive symptoms in postmenopausal women and may enhance antidepressant response for older women with major depression.
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PMID:Depression in the medical setting: biopsychological interactions and treatment considerations. 1008 82

Thalamic neurons are known to switch their firing from a tonic pattern during wakefulness to a bursting pattern during sleep. Several studies have described the existence of bursting activity in awake chronic pain patients and have suggested that this activity is abnormal and may be related to their pain. However, we have frequently observed bursting activity in awake non-pain patients suggesting that there may not be a causal relationship between thalamic bursting activity and chronic pain. To examine this issue more rigorously we compared the incidence and pattern of bursting activity of lateral thalamic neurons of both pain and non-pain patients in a state of wakefulness. Recordings were obtained from lateral thalamic areas of different groups of patients (n = 91) suffering from pain disorders (e.g. anaesthesia dolorosa, phantom limb pain, trigeminal neuralgia, post-stroke pain) and motor disorders (e.g. Parkinson's disease, essential tremor) during stereotactic surgical procedures for the treatment of pain and movement disorders. Burst indices (the number of bursting cells per electrode track) were computed for all the explorations in the two groups. The burst indices in the pain and non-pain groups (1.73 +/- 0.28 and 1.14 +/- 0.16, respectively) were not significantly different from each other. The bursts were analyzed to see if they fulfilled the criteria of low-threshold calcium spike (LTS)-evoked bursts characterized by (i) a shortening of the first interspike interval with an increase in the number of interspike intervals in the burst and also (ii) a progressive prolongation of successive interspike intervals. LTS-evoked bursts were identified in 27/47 (57%) bursting cells in pain patients and 15/32 (47%) cells in non-pain patients. These data demonstrate that the occurrence of bursting activity and of LTS-evoked bursts in the human thalamus is prevalent in both pain and non-pain patients. This suggests that the bursting activity of thalamic neurons in pain patients is not necessarily related to the occurrence of their pain.
Pain 1999 Apr
PMID:A comparison of the burst activity of lateral thalamic neurons in chronic pain and non-pain patients. 1034 18


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