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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain states are accompanied by increased sensitivity to both noxious and non-noxious sensory stimuli, characterized as hyperalgesia and allodynia, respectively. In animal models of neuropathic pain, the presence of hyperalgesia and allodynia are accompanied by neuroplastic changes including increased spinal levels of substance P, cholecystokinin (CCK), and dynorphin. N-Methyl-D-aspartate (NMDA) receptors appear to be involved in maintaining the central sensitivity which contributes to neuropathic pain. In addition to its opioid activities, dynorphin has been suggested to act at the NMDA receptor complex. In an attempt to mimic the increased levels of spinal dynorphin seen in animal models of neuropathic pain, rats received a single intrathecal (i.t.) injection of dynorphin A(1-17), dynorphin A(1-13), dynorphin A(2-17) or dynorphin A(2-13) through indwelling catheters. Tactile allodynia was determined by measuring response threshold to probing with von Frey filaments. Dynorphin A(1-17) administration evoked significant and long-lasting tactile allodynia (i.e. > 60 days). Likewise, the i.t. administration of dynorphin A(1-13) or dynorphin A(2-17) or dynorphin A(2-13) also produced long-lasting tactile allodynia. Intrathecal pretreatment, but not post-treatment, with MK-801 prevented dynorphin A(1-17)-induced development of allodynia; i.t. administration of MK-801 alone had no effect on responses to tactile stimuli. In contrast, i.t. pretreatment with naloxone did not affect the development of tactile allodynia induced by dynorphin A(1-17) or alter sensory threshold when given alone. These results demonstrate that a single dose of dynorphin A, or its des-Tyr fragments, produces long-lasting allodynia which may be irreversible in the rat. Further, this effect appears to be mediated through activation of NMDA, rather than opioid, receptors. While the precise mechanisms underlying the development and maintenance of the allodynia is unclear, it seems possible that dynorphin may produce changes in the spinal cord, which may contribute to the development of signs reminiscent of a "neuropathic' state. Given that levels of dynorphin are elevated following nerve injury, it seems reasonable to speculate that dynorphin may have a pathologically relevant role in neuropathic pain states.
Pain 1996 Dec
PMID:Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone. 912 15

Neuropathic pain is poorly managed by conventional analgesic therapy, such as non-steroidal anti-inflammatory drugs and opiates. The development of animal models of peripheral neural damage has aided in our understanding of the pathology and pharmacology of neuropathic pain. This report is the first clear demonstration using selective neurokinin-1 receptor antagonists of a potentially novel therapeutic approach to the treatment of neuropathic pain resulting from peripheral nerve damage in a guinea-pig model. The neurokinin-1 receptor antagonists, SDZ NKT 343 and LY 303,870 significantly reduced mechanical hyperalgesia following oral and intrathecal administration. (R,R)-SDZ NK T343, the enantiomer of SDZ NKT 343 did not show anti-hyperalgesic activity. RPR 100,893 showed significant anti-hyperalgesic activity only following intrathecal administration suggesting poor absorption or low level penetration of the blood-brain barrier. These results imply that neurokinin-1 receptor antagonists offer a new class of anti-hyperalgesic drugs with a largely central site of action in neuropathic pain.
Neuroscience 1998 Dec
PMID:Selective neurokinin-1 receptor antagonists are anti-hyperalgesic in a model of neuropathic pain in the guinea-pig. 975 19

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.
Drug Ther Bull 2000 Dec
PMID:Drug treatment of neuropathic pain. 1122 Nov 84

Paclitaxel, an effective anti-neoplastic agent in the treatment of solid tumors, produces a dose-limiting painful peripheral neuropathy in a clinically significant number of cancer patients. Prior work has demonstrated paclitaxel-induced neurodegeneration and sensory loss in laboratory rodents. We describe here an experimental paclitaxel-induced painful peripheral neuropathy. Adult male rats were given four intraperitoneal injections on alternate days of vehicle or 0.5, 1.0, or 2.0 mg/kg of paclitaxel (Taxol). Behavioral tests for pain using mechanical and thermal stimuli applied to the tail and hind paws, and tests for motor performance, were taken before, during and after dosing for 22-35 days. All three doses of paclitaxel caused heat-hyperalgesia, mechano-allodynia, mechano-hyperalgesia, and cold-allodynia, but had no effect on motor performance. Neuropathic pain began within days and lasted for several weeks. We did not detect any dose-response relationship. Tests at the distal, mid, and proximal tail failed to show evidence of a length-dependent neuropathy. Vehicle control injections had no effect on any measure. No significant systemic toxicities were noted in the paclitaxel-treated animals. Light-microscopic inspection of the sciatic nerve (mid-thigh level), L4-L5 dorsal root ganglia, and dorsal and ventral roots, and the gray and white matter of the L4-L5 spinal cord, showed no structural abnormalities. Electron microscopic examination of the sciatic nerve (mid-thigh level) and the L4-L5 dorsal root ganglia and dorsal horns demonstrated no degeneration of myelinated and unmyelinated axons in the sciatic nerve and roots, but revealed endoneurial edema. This model may be useful in understanding a significant source of pain in cancer patients, and in finding ways to avoid the neurotoxicity that limits paclitaxel therapy.
Pain 2001 Dec
PMID:A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel. 1173 Oct 66

Co-localization of opioid and melanocortin receptor expression, especially at the spinal cord level in the dorsal horn and in the gray matter surrounding the central canal led to the suggestion that melanocortins might play a role in nociceptive processes. In the present studies, we aimed to determine the effects of melanocortins, administered intrathecally, on allodynia, and to ascertain whether there is an interaction between opioid and melanocortin systems at the spinal cord level. Neuropathic pain was induced by chronic constriction injury (CCI) of the right sciatic nerve in rats. Tactile allodynia was assessed using von Frey filaments, while thermal hyperlagesia was evaluated in cold water allodynia test. In the present experiments, melanocortin receptor antagonist, SHU9119 was much more potent than mu-opioid receptor agonist, morphine after their intrathecal (i.th.) administration in neuropathic rats. SHU9119 alleviated allodynia in a comparable manner to DAMGO, a selective and potent mu-opioid receptor agonist. Administration of melanocortin receptor agonist, melanotan-II (MTII) increased the sensitivity to tactile and cold stimulation. Moreover, we demonstrated that the selective blockade of mu-opioid receptor by cyprodime (CP) enhanced antiallodynic effect of SHU9119 as well as pronociceptive action of MTII, whereas the combined administration of mu receptor agonist (DAMGO) and SHU9119 significantly reduced the analgesic effect of those ligands. DAMGO also reversed the proallodynic effect of melanocortin receptor agonist, MTII. In conclusion, it seems that the endogenous opioidergic system acts as a functional antagonist of melanocortinergic system, and mu-opioid receptor activity appears to be involved in the modulation of melanocortin system function.
Neuroreport 2002 Dec 20
PMID:Modulation of melanocortin-induced changes in spinal nociception by mu-opioid receptor agonist and antagonist in neuropathic rats. 1249 47

Neuropathic pain is a major problem in the treatment of cancer pain. We performed a retrospective analysis of 213 cancer patients with neuropathic pain treated by a pain service following the World Health Organization guidelines for relief of cancer pain. Of these, 79% presented with nerve compression pain, 16% with nerve injury pain, and 5% with sympathetically-maintained pain. Whereas nerve compression and nerve injury pain were caused most frequently by cancer growth, sympathetically-maintained pain was caused most frequently by cancer treatment. There were no significant differences in the use of analgesics, the mean pain intensity, or the efficacy of analgesic treatment among the three groups. Nerve injury pain and sympathetically-maintained pain were treated more frequently with adjuvant analgesics, especially antidepressants and anticonvulsants. The variety of different neuropathic pain syndromes should be separated in future studies of the efficacy of different treatment approaches.
J Pain Symptom Manage 2003 Dec
PMID:Analysis and treatment of different types of neuropathic cancer pain. 1465 64

Neuropathic pain that results from injury to the peripheral or CNS responds poorly to opioid analgesics. Y1 and Y2 receptors for neuropeptide Y (NPY) may, however, serve as targets for analgesics that retain their effectiveness in neuropathic pain states. In substantia gelatinosa neurons in spinal cord slices from adult rats, we find that NPY acts via presynaptic Y2 receptors to attenuate excitatory postsynaptic currents (EPSCs) and predominantly on presynaptic Y1 receptors to attenuate glycinergic and GABAergic inhibitory postsynaptic currents (IPSCs). Because NPY attenuates the frequency of TTX-resistant miniature EPSCs and IPSCs, perturbation of the neurotransmitter release process contributes to its actions at both excitatory and inhibitory synapses. These effects, which are reminiscent of those produced by analgesic opioids, provide a cellular basis for previously documented spinal analgesic actions mediated via Y1 and Y2 receptors in neuropathic pain paradigms. They also underline the importance of suppression of inhibition in spinal analgesic mechanisms.
J Neurophysiol 2004 Dec
PMID:Opioid-like actions of neuropeptide Y in rat substantia gelatinosa: Y1 suppression of inhibition and Y2 suppression of excitation. 1529 7

Neuropathic pain (NP), caused by a primary lesion or dysfunction in the nervous system, affects approximately 4 million people in the United States each year. It is associated with many diseases, including diabetic peripheral neuropathy, postherpetic neuralgia, human immunodeficiency virus-related disorders, and chronic radiculopathy. Major pathophysiological mechanisms include peripheral sensitization, sympathetic activation, disinhibition, and central sensitization. Unlike most acute pain conditions, NP is extremely difficult to treat successfully with conventional analgesics. This article introduces a contemporary management approach, that is, one that incorporates nonpharmacological, pharmacological, and interventional strategies. Some nonpharmacological management strategies include patient education, physical rehabilitation, psychological techniques, and complementary medicine. Pharmacological strategies include the use of first-line agents that have been supported by randomized controlled trials. Finally, referral to a pain specialist may be indicated for additional assessment, interventional techniques, and rehabilitation. Integrating a comprehensive approach to NP gives the primary care physician and patient the greatest chance for success.
Mayo Clin Proc 2004 Dec
PMID:Contemporary management of neuropathic pain for the primary care physician. 1559 38

Neuropathic pain is caused by damage to the nervous system. Unlike physiologic pain (also known as nociceptive pain), neuropathic pain is not self-limited and is not as easily treated. The etiologic causes of neuropathic pain are many and varied in their scope. These include infectious agents, metabolic disease, neurodegenerative disease, and physical trauma, among others. Clinically, a high degree of variability exists between patients in their response to treatment. The pathophysiology of neuropathic pain syndromes is complex. However, current research is rapidly expanding our understanding of these syndromes. Numerous cellular mechanisms of pain transmission have been elucidated, and the clinical correlates of these mechanisms are beginning to be recognized. As our knowledge base continues to grow, we anticipate the development of improved treatments for the benefit of our patients with pain.
Pain Manag Nurs 2004 Dec
PMID:Pathophysiology of neuropathic pain. 1564 54

Patients with neuropathic pain present a clinical challenge. Neuropathic pain, when chronic, often leads to disability. Diagnosis can be difficult because both positive and negative sensory and motor signs and symptoms may be present, as well as a variety of comorbid conditions. In addition, there may be a high degree of interpatient variability. Currently, clinical evaluation, rather than diagnostic tests, is one of the best available tools for assessment and diagnosis. As with all chronic pain conditions, the key to a thorough assessment is a thorough history that includes medical, functional, and psychosocial evaluations. Currently available pain assessment tools, which are widely used in nursing practice, are still inadequate for use in patients with neuropathic pain. The physical and neurologic examination remains a critical element for patient evaluation. This includes an assessment of spontaneous pain (continuous or intermittent), pain evoked by daily activities (allodynia), and other abnormal sensations that are not necessarily painful (paresthesias, dysesthesias). Sensitivity to pinprick, touch, pressure, cold, heat, and vibration are measured, often confirming the suspected diagnosis. Patients may be confused by the unusual sensations they are experiencing and unable to effectively describe or communicate their symptoms. This communication barrier may contribute to an inadequate physical examination. With improved skills in patient assessment and through enhanced communication with patients, nurses can make an important contribution to treatment outcomes in patients with neuropathic pain.
Pain Manag Nurs 2004 Dec
PMID:Neuropathic pain: a guide to comprehensive assessment. 1564 55


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