Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotrophins (NTs) belong to a family of structurally and functionally related proteins, they are the subsets of neurotrophic factors. Neurotrophins are responsible for diverse actions in the developing peripheral and central nervous systems. They are important regulators of neuronal function, affecting neuronal survival and growth. They are able to regulate cell death and survival in development as well as in pathophysiologic states. NTs and their receptors are expressed in areas of the brain that undergo plasticity, indicating that they are able to modulate synaptic plasticity.Recently, neurotrophins have been shown to play significant roles in the development and transmission of neuropathic pain. Neuropathic pain is initiated by a primary lesion or dysfunction in the nervous system. It has a huge impact on the quality of life. It is debilitating and often has an associated degree of depression that contributes to decreasing human well being. Neuropathic pain ranks at the first place for sanitary costs.Neuropathic pain treatment is extremely difficult. Several molecular pathways are involved, making it a very complex disease. Excitatory or inhibitory pathways controlling neuropathic pain development show altered gene expression, caused by peripheral nerve injury. At present there are no valid treatments over time and neuropathic pain can be classified as an incurable disease.Nowadays, pain research is directing towards new molecular methods. By targeting neurotrophin molecules it may be possible to provide better pain control than currently available.
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PMID:Role of neurotrophins in neuropathic pain. 2265 13

Clinically, it is well-known that chronic pain induces depression, anxiety, and reduced quality of life. Neuropathic pain, which is characterized by spontaneous burning pain, hyperalgesia and allodynia, is the most difficult pain to manage in the pain clinic. However, the complicated pathophysiology of neuropathic pain is not yet understood. A better understanding of its pathophysiology has given us more insight into its various mechanisms and possible treatment options. This review will explore the most current issues in the field of pain, with a focus on transcriptional research, epigenetic research and post-transcriptional research. For a global understanding of the pain, it is necessary to analyze the correlation between these temporal parameters and phenomics.
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PMID:[Global understanding of pain]. 2270 58

Neuropathic pain (NP) often presents with comorbidities, including depression and anxiety. The amygdala is involved in the processing of mood disorders, fear, and the emotional-affective components of pain. Hemispheric lateralization of pain processing in the amygdala has recently been brought to light because, independently of the side of the peripheral injury, the right central nucleus of the amygdala (CeA) showed higher neuronal activity than the left in models of inflammatory pain. Although the CeA has been called the 'nociceptive amygdala', because of its high content of nociceptive neurones, little is known about changes in its neuronal function in vivo, under NP conditions. Herein, we quantified CeA spontaneous and evoked activity in rats subjected to spinal nerve ligation (SNL), under isoflurane anaesthesia, following application of mechanical and thermal stimuli to widespread body areas. We found that spontaneous and stimulus-evoked neuronal activity was higher in the left CeA at 2 and 6 days after SNL induction and declined afterwards, whereas activity in the right CeA became dominant at 14 days after surgery, independently of the side of surgery. We also observed that systemic injection of pregabalin, which is widely used in patients with NP, reduced CeA spontaneous and stimulus-evoked neuronal activity. Overall, we observed that peripheral nerve injury produced asymmetric plasticity in ongoing and evoked activity in the left and right CeA. Remarkably, at 14 days after SNL induction, enhanced evoked activity in the right CeA persisted compared to short-term increases in activity in the left CeA. The plasticity found in ongoing and evoked activity was inhibited by pregabalin.
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PMID:Asymmetric time-dependent activation of right central amygdala neurones in rats with peripheral neuropathy and pregabalin modulation. 2286 Nov 66

Pain is an unpleasant, sensitive and emotional experience associated with or described in terms of tissue lesion, and may be acute or chronic. It may also be classified as nociceptive, neuropathic or psychogenic. Nociceptive pain involves the transformation of environmental stimuli into action potentials carried to the central nervous system, where they are modulated and integrated up to final interpretation in the cerebral cortex. Neuropathic pain may arise as a consequence of the direct lesion of axons, or of an increase in the production of neurotrophic factors. Chronic pain is always associated with anxiety and some degree of depression. Drug therapy should be selected according to its efficacy; nonetheless, the professional should also consider the tolerability and adverse effects that may occur, for example, in elderly individuals. It is necessary to emphasize the safety-considering the possibility of drug interactions-and define the posology to promote better adherence. However, the treatment of neuropathic pain should not be limited to the use of analgesic drugs, which are just one among several options enabling patients to participate in bio-psycho-social rehabilitation programs.
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PMID:Mechanisms and clinical management of pain. 2331 53

Neuropathic pain represents a diagnostic challenge and is difficult to treat. In recent years, clinical trials have led to the development of a number of new treatment guidelines. The guidelines recommend drugs for the most important types of neuropathic pain and suggest alternatives in the event of lack of effect or intolerable adverse effects. Patients with this condition often suffer from anxiety, depression and insomnia, which influences the choice of drug. This article presents the most important drugs on which these guidelines concur.
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PMID:[Medical treatment of neuropathic pain]. 2365 47

Neuropathic pain is the most common type of pain in neuropathy. In painful polyneuropathies the pain usually has a "glove and stocking" distribution. The pain may be predominantly spontaneous, e.g., with a burning, pricking, or shooting character or characterized by evoked pain such as mechanical or cold allodynia. In the clinical setting, the prevention of painful neuropathies and treatment of underlying neuropathy remains inadequate and thus symptomatic treatment of the pain and related disability needs to be offered. Most randomized, double-blind, placebo-controlled trials (RCTs) published in painful neuropathy have been conducted in patients with diabetes and to what extent a treatment which is found effective in painful diabetic polyneuropathy can be expected to relieve other conditions like chemotherapy- or HIV-induced neuropathy is unknown. Tricyclic antidepressants (TCAs), gabapentin, pregabalin, and serotonin noradrenaline reuptake inhibitors (SNRIs) are first drug choices. In patients with localized neuropathic pain, a topical lidocaine patch may also be considered. Second-line treatments are tramadol and other opioids. New types of treatment include botulinum toxin type A (BTX-A), high-dose capsaicin patches, and cannabinoids. Other types of anticonvulsant drugs such as lamotrigine, oxcarbazepine, and lacosamide have a more questionable efficacy in painful polyneuropathy but may have an effect in a subgroup of patients. Combination therapy may be considered in patients with insufficient effect from one drug. Treatment is usually a trial-and-error process and has to be individualized to the single patient, taking into account all comorbidities such as possible concomitant depression, anxiety, diseases, and drug interactions. Side-effects to antidepressants include dry mouth, nausea, constipation, orthostatic hypotension, and sedation. ECG should always be obtained prior to treatment with TCAs, which also should not be used in patients with cardiac incompensation and epilepsy. The most common side-effects of gabapentin and pregabalin are CNS-related side-effects with dizziness and somnolence. Peripheral edema, weight gain, nausea, vertigo, asthenia, dry mouth, and ataxia may also occur. Topical treatments are better tolerated due to lack of systemic side-effects but there is still limited evidence for the long-term efficacy of these drugs. With available drugs, the average pain reduction is about 20-30%, and only 20-35% of the patients will achieve at least 50% pain reduction, which stresses the need of a multidisciplinary approach to pain treatment.
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PMID:Management of painful neuropathies. 2393 87

The pain matrix is conceptualised here as a fluid system composed of several interacting networks. A nociceptive matrix receiving spinothalamic projections (mainly posterior operculoinsular areas) ensures the bodily specificity of pain and is the only one whose destruction entails selective pain deficits. Transition from cortical nociception to conscious pain relies on a second-order network, including posterior parietal, prefrontal and anterior insular areas. Second-order regions are not nociceptive-specific; focal stimulation does not evoke pain, and focal destruction does not produce analgesia, but their joint activation is necessary for conscious perception, attentional modulation and control of vegetative reactions. The ensuing pain experience can still be modified as a function of beliefs, emotions and expectations through activity of third-order areas, including the orbitofrontal and perigenual/limbic networks. The pain we remember results from continuous interaction of these subsystems, and substantial changes in the pain experience can be achieved by acting on each of them. Neuropathic pain (NP) is associated with changes in each of these levels of integration. The most robust abnormality in NP is a functional depression of thalamic activity, reversible with therapeutic manoeuvres and associated with rhythmic neural bursting. Neuropathic allodynia has been associated with enhancement of ipsilateral over contralateral insular activation and lack of reactivity in orbitofrontal/perigenual areas. Although lack of response of perigenual cortices may be an epiphenomenon of chronic pain, the enhancement of ipsilateral activity may reflect disinhibition of ipsilateral spinothalamic pathways due to depression of their contralateral counterpart. This in turn may bias perceptual networks and contribute to the subjective painful experience.
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PMID:Pain matrices and neuropathic pain matrices: a review. 2402 62

The term "neuropathic pain" (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain's surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include "frameless stereotactic" neuronavigation systems, in which patients' head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.
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PMID:Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain-At the Tipping Point? 2422 66

Neuropathic pain can develop after nerve injury, when deleterious changes occur in injured neurons and along nociceptive and descending modulatory pathways in the central nervous system. The myriad neurotransmitters and other substances involved in the development and maintenance of neuropathic pain also play a part in other neurobiological disorders. This might partly explain the high comorbidity rates for chronic pain, sleep disorders, and psychological conditions such as depression, and why drugs that are effective for one condition may benefit others. Neuropathic pain can be distinguished from non-neuropathic pain by two factors. Firstly, in neuropathic pain there is no transduction (conversion of a nociceptive stimulus into an electrical impulse). Secondly, the prognosis is worse: injury to major nerves is more likely than injury to non-nervous tissue to result in chronic pain. In addition, neuropathic pain tends to be more refractory than non-neuropathic pain to conventional analgesics, such as non-steroidal anti-inflammatory drugs and opioids. However, because of the considerable overlap between neuropathic and nociceptive pain in terms of mechanisms and treatment modalities, it might be more constructive to view these entities as different points on the same continuum. This review focuses on the mechanisms of neuropathic pain, with special emphasis on clinical implications.
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PMID:Neuropathic pain: mechanisms and their clinical implications. 2450 Apr 12

Pain initiated or caused by a primary lesion or dysfunction in the nervous system is defined as neuropathic pain. About 75 -150 million people in the United States are suffering for chronic pain disorder. Neuropathic pain has a great impact on the human wellbeing. It is very debilitating and often has an associated degree of depression that contributes to decreasing the quality of life. Moreover, the management of chronic pain is costly to the health care system. Pain is a national healthcare priority in US: the United States Congress has declared the present decade (2001-2010) as the "Decade of Pain Control and Research". Neuropathic pain is a very complex disease, involving several molecular pathways. Due to its individual character, its treatment is extremely difficult. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. Nowadays, pain research is focusing on newer molecular ways, such as stem cell therapy, gene therapy, and viral vectors for delivery of biologic anti-nociceptive molecules. These methods could provide a new therapeutic approach to neuropathic pain relief.
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PMID:Stem cell therapy for neuropathic pain treatment. 2469 13


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