Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line-derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states.
 ...
PMID:Potent analgesic effects of GDNF in neuropathic pain states. 1102 95

Although progress in cancer research is paralleled by the discovery and development of novel chemotherapeutic agents, the benefits of these agents are offset by their side-effect profiles. Of the numerous adverse effects associated with antineoplastic drugs, peripheral neuropathy is the most frequent and is often debilitating. This article reviews the treatment options--both primary and secondary--for neuropathic complications of cancer therapy. Before a potentially neurotoxic chemotherapeutic regimen is started, patients should undergo 1) a baseline neurologic history for possible coexisting risk factors for neuropathy; 2) physical evaluation; and 3) if indicated, electrophysiologic testing, including nerve conduction studies and electromyography. Patients should be followed closely for the development of neuropathic signs and symptoms. When symptoms (eg, paresthesias or pain) or deficits (eg, weakness) develop, their severity and their effect on quality of life will determine whether the neurotoxic chemotherapy should be continued at a lower dose or discontinued. Neuropathic pain should be treated aggressively with a stepwise approach. The decision to initiate therapy should be guided first by the severity of pain and second by the convenience of dosing and the side-effect profile of the medication. Specific antineuropathic pain therapy may begin with a tricyclic antidepressant (TCA), titrated to 100 to 150 mg/d, unless anticholinergic side effects appear before this dosage is reached. The TCA may be replaced by or supplemented with antiepileptic agents, such as gabapentin, which is attractive because of its rapid dose titration (maximum, 3600 mg/d) and minimal interaction with other medications. In addition to pharmacologic therapies targeting symptom management, new therapies directed at preventing the onset or progression of neurotoxicity are desperately needed.
 ...
PMID:Neurologic Complications of Cancer Therapy. 1109 27

The word "pain" is ambiguous, symbolic and it is understood differently by the patient and by the doctor or physiologist. It describes a kind of sensation evoked by harmful stimuli which is a physiological phenomenon indispensable for protection and also suffering caused by injury or disease. The second component of the phenomenon is usually not recognized--this is the reaction to pain. The primary component is centripetal and ascending to brain centers, the second is centrifugal, descending and they both form the reflex arc. This is the pain or nociceptive reflex. Commonly, when we speak of pain we mean only the centripetal part of the reflex which cannot be objectively assessed in medical practise. This part is blocked by anaesthesia before surgical procedures. The second part is the subject of a separate consideration which begins with psychic reaction to pain and pain tolerance, and suffering depend on it. The motor reaction to pain is more spectacular and possible for recording. Three types of this reaction are discerned: flight, defense and suffering expression. Nociceptive sensation is a physiological receptor-mediated sensation, while pathological pain can derive from receptors as well as from nerves /conduction pain, neuropathic differentiation pain/ or from centres/central pain. The pathological pain has clinical features making possible the recognition of its origin, its mechanism for undertaking of appropriate measures. Neuropathic pain is the one most difficult to treat. The receptor-mediated pain continues as long as the stimulus is active, the neuropathic pain is longer lasting.
 ...
PMID:[Pain--physiological or medical phenomenon]. 1110 60

Neuropathic pain, a form of chronic pain caused by injury to or disease of the peripheral or central nervous system, is a formidable therapeutic challenge to clinicians because it does not respond well to traditional pain therapies. Our knowledge about the pathogenesis of neuropathic pain has grown significantly over last 2 decades. Basic research with animal and human models of neuropathic pain has shown that a number of pathophysiological and biochemical changes take place in the nervous system as a result of an insult. This property of the nervous system to adapt morphologically and functionally to external stimuli is known as neuroplasticity and plays a crucial role in the onset and maintenance of pain symptoms. Many similarities between the pathophysiological phenomena observed in some epilepsy models and in neuropathic pain models justify the rational for use of anticonvulsant drugs in the symptomatic management of neuropathic pain disorders. Carbamazepine, the first anticonvulsant studied in clinical trials, probably alleviates pain by decreasing conductance in Na+ channels and inhibiting ectopic discharges. Results from clinical trials have been positive in the treatment of trigeminal neuralgia, painful diabetic neuropathy and postherpetic neuralgia. The availability of newer anticonvulsants tested in higher quality clinical trials has marked a new era in the treatment of neuropathic pain. Gabapentin has the most clearly demonstrated analgesic effect for the treatment of neuropathic pain, specifically for treatment of painful diabetic neuropathy and postherpetic neuralgia. Based on the positive results of these studies and its favourable adverse effect profile, gabapentin should be considered the first choice of therapy for neuropathic pain. Evidence for the efficacy of phenytoin as an antinociceptive agent is, at best, weak to modest. Lamotrigine has good potential to modulate and control neuropathic pain, as shown in 2 controlled clinical trials, although another randomised trial showed no effect. There is potential for phenobarbital, clonazepam, valproic acid, topiramate, pregabalin and tiagabine to have antihyperalgesic and antinociceptive activities based on result in animal models of neuropathic pain, but the efficacy of these drugs in the treatment of human neuropathic pain has not yet been fully determined in clinical trials. The role of anticonvulsant drugs in the treatment of neuropathic pain is evolving and has been clearly demonstrated with gabapentin and carbamazepine. Further advances in our understanding of the mechanisms underlying neuropathic pain syndromes and well-designed clinical trials should further the opportunities to establish the role of anticonvulsants in the treatment of neuropathic pain.
 ...
PMID:Anticonvulsants for neuropathic pain syndromes: mechanisms of action and place in therapy. 1112 21

Neuropathic pain is a distressing, poorly understood and under-treated condition. In this review we seek to examine the definition and classification of neuropathic pain, summarize clinically important underlying mechanisms, outline current management strategies and look at future directions for research and therapy.
 ...
PMID:Neuropathic pain. 1119 43

Neuropeptide Y (NPY) is believed to exert antinociceptive actions by inhibiting the release of substance P and other 'pain neurotransmitters' in the spinal cord dorsal horn. However, the physiological significance and potential therapeutic value of NPY remain obscure. It is also unclear which receptor subtype(s) are involved. To identify a possible physiological role for the NPY Y1 receptor in pain transmission, we generated NPY Y1 receptor null mutant (Y1-/-) mice by homologous recombination techniques. Here we show that Y1-/- mice develop hyperalgesia to acute thermal, cutaneous and visceral chemical pain, and exhibit mechanical hypersensitivity. Neuropathic pain is increased, and the mice show a complete absence of the pharmacological analgesic effects of NPY. In the periphery, Y1 receptor activation is sufficient and required for substance P release and the subsequent development of neurogenic inflammation and plasma leakage. We conclude that the Y1 receptor is required for central physiological and pharmacological NPY-induced analgesia and that its activation is both sufficient and required for the release of substance P and initiation of neurogenic inflammation.
 ...
PMID:Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. 1120 47

Neuropathic pain results from damage to or dysfunction in the nervous system. The term usually refers to pain caused by a primary abnormality in the peripheral nervous system, while pain caused by damage to the central nervous system tends to be called central pain. Once established, neuropathic pain frequently runs a chronic course and can be severe and difficult to treat. Most doctors (but especially GPs, neurologists, neurosurgeons, oncologists and pain clinic specialists) will encounter patients with neuropathic pain. Management, ideally in a multidisciplinary pain-relief clinic, often involves the combined use of a range of pharmacological and non-drug approaches, the latter including transcutaneous electrical nerve stimulation, psychological treatments, and specialist procedures to stimulate, block or destroy discrete areas of the nervous system. Here, we review just the drug treatments for neuropathic pain.
 ...
PMID:Drug treatment of neuropathic pain. 1122 Nov 84

Neuropathic pain, or pain after nervous system injury, can be very refractory to pharmacologic interventions. Through a better understanding of the pathophysiology of neuropathic pain, it has been suggested that nonopioid agents, such as antidepressants and anticonvulsants, may be more efficacious in the treatment of neuropathic pain than common analgesics, such as opioids or nonsteroidal anti-inflammatory drugs. However, this has not been consistently demonstrated in clinical studies. Conversely, many confounding factors of neuropathic pain make it difficult to interpret clinical studies. Therefore, we must develop a better understanding of the preclinical models of neuropathic pain to better understand the application of new and old drugs to the human neuropathic pain state. This article provides an overview of the commonly used preclinical neuropathic pain models, followed by a summary of the efficacy of currently available agents in preclinical pain models and human correlates.
 ...
PMID:Pharmacologic treatment of neuropathic pain. 1125 48

Neuropathic pain is seen in a third of cancer patients and is not always responsive to traditional analgesics. We describe practical guidelines for the use antidepressants and anticonvulsants as adjuvant analgesics in such situations. Newer adjuvant analgesics, interventional procedures and options for the management of pain emergencies, are also briefly outlined.
 ...
PMID:The management of neuropathic pain in cancer: clinical guidelines for the use of adjuvant analgesics. 1126 Dec 35

Neuropathic pain, due to peripheral nerve damage, can include allodynia (perception of innocuous stimuli as being painful), hyperalgesia (increased sensitivity to noxious stimuli) and spontaneous pain, often accompanied by sensory deficits. Plasticity in transmission and modulatory systems are implicated in the underlying mechanisms. The Kim and Chung rodent model of neuropathy (Kim and Chung, Pain 50 (1992) 355) employed here involves unilateral tight ligation of two (L5 and L6) of the three (L4, L5, and L6) spinal nerves of the sciatic nerve and reproducibly induced mechanical and cold allodynia in the ipsilateral hindpaw over the 14 day post-operative period. In vivo electrophysiological techniques have then been used to record the response of dorsal horn neurones to innocuous and noxious electrical and natural (mechanical and thermal) stimuli after spinal nerve ligation (SNL). Activation of voltage-dependent calcium channels (VDCCs) is critical for neurotransmitter release and neuronal excitability, and antagonists can be antinociceptive. Here, for the first time, the effect of N- and P-type VDCC antagonists (omega-conotoxin-GVIA and omega-agatoxin-IVA, respectively) on the evoked dorsal horn neuronal responses after neuropathy have been investigated. Spinal omega-conotoxin-GVIA (0.1-3.2 microg) produced prolonged inhibitions of both the electrically- and low- and high-intensity naturally-evoked neuronal responses in SNL and control rats. Spinal omega-agatoxin-IVA (0.1-3.2 microg) also had an inhibitory effect but to a lesser extent. After neuropathy the potency of omega-conotoxin-GVIA was increased at lower doses in comparison to control. This indicates an altered role for N-type but not P-type VDCCs in sensory transmission after neuropathy and selective plasticity in these channels after nerve injury. Both pre- and post-synaptic VDCCs appear to be important.
 ...
PMID:Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy. 1132 45


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