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

Pain is the primary reason for patients seeking healthcare, and it has been estimated to result in more than dollar 100 billion per year in direct medical costs. Neuropathic pain (NP) alone has been associated with an approximately 3-fold increase in use of healthcare resources. The indirect costs associated with chronic pain result from increased absenteeism and decreased productivity at work, and they also have been estimated to total dollar 100 billion each year in the United States. NP contributes substantially to these costs. Results from one study indicated that employment was affected in 43% of patients with NP. Quality of life is also significantly reduced in such patients. Patients with chronic pain also have difficulty in initiating and maintaining sleep, and sleep deprivation has the potential to exacerbate pain. Sleep deprivation is also associated with both anxiety and depression, and both of these conditions can exacerbate sleep disturbances. Effective management of the patient with chronic pain, including NP, requires assessment and, if necessary, treatment of all comorbidities associated with this condition.
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PMID:Consequences of neuropathic pain: quality-of-life issues and associated costs. 1677 58

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.
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PMID:Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat. 1729 2

Neuropathic pain is a type of chronic pain following central or peripheral nervous system lesions that cause allodynia (pain initiated by a non-painful stimulus) and hyperalgesia (increased pain sensation following a painful stimulus). The first objective of the study was to evaluate the pharmacokinetics of eugenol, the principle chemical constituent of clove oil, following a gavage administration (40 mg/kg) in male Sprague-Dawley rats. The second objective was to evaluate the effect of repeated oral administrations of eugenol on hyperalgesia and allodynia using an experimental model of neuropathic pain in rats. Thermal and mechanical sensitivity (Hargreave's test and von Frey filaments) were determined in sciatic nerve cuff-implanted rats. Sensitivities were assessed following repeated oral administrations of 40 mg/kg of eugenol or saline for 5 days (n=6 per group). Pharmacokinetic parameters were calculated using noncompartmental methods. Serial blood samples were collected over 24 h. Concentrations of eugenol in blood and plasma peaked rapidly following oral administration. Mean T(1/2) values of eugenol in plasma and blood were long (14.0 and 18.3 h, respectively), suggesting a potential accumulation of the drug following repeated administrations. Reaction time to thermal stimuli appeared to increase constantly following repeated administrations of eugenol. On the last day of treatment, eugenol treatments resulted in a statistically significant prolongation of the reaction time to thermal stimuli in rats compared to the saline group (Mean+/-S.E.M.: 11.4+/-1.23 vs. 6.1+/-0.53 s, P<0.01). These results support the hypothesis that eugenol may alleviate neuropathic pain and that the cumulative effect of the drug may be in part responsible for this effect following repeated daily administrations.
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PMID:Pharmacokinetics of eugenol and its effects on thermal hypersensitivity in rats. 1732 20

The pain remaining after a needle stick is categorized as neuropathic pain. CRPS (Complex Regional Pain Syndrome) is a typical disease in this category. Neuropathic pain is extremely intractable when it becomes chronic pain, inducing psychological and physical pain in patients over a long period of time. Neuropathic pain is a complex system caused by various factors, and its mechanism remains unclear. For prevention, medical practioners should carefully select centesis, and apply necessary measures corresponding to the situation. There is no established treatment for neuropathic pain. We usually treat the disease with nerve block and drug therapy. Nerve block is useful for pain relief. We typically use a sympathetic nerve block (SGB; stellate ganglion block, IRSB; intravenous regional sympathetic block et. al.) as the initial treatment. In the stage of chronic pain, it is very important to improve patients' ADL (activity of daily living) and QOL (quality of life). If neuropathic pain is suspected, it is crucial to treat at an early stage. Therefore, it should be emphasized that when pain persists after a needle stick, the patient should immediately consult a pain clinician or an orthopedist.
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PMID:[Iatrogenic peripheral nerve injury; mechanism and therapy]. 1744 68

Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the nervous system. It is estimated that 75-150 million people in the United States have a chronic pain disorder. Neuropathic pain has a great impact on the quality of life. It is debilitating and often has an associated degree of depression that contributes to decreasing human wellbeing. Moreover, the management of chronic pain is costly to the health care system. The United States Congress has declared the present decade (2001-2010) as the "Decade of Pain Control and Research", making pain a national healthcare priority. In Europe, statistics provided by the International Association on the Study of Pain (IASP) and the European Federation of the IASP Chapters (EFIC) indicate that one in five people suffer from moderate to severe chronic pain, and that one in three are unable or less able to maintain an independent lifestyle due to their pain. Between one-half and two-thirds of people with chronic pain are less able or unable to exercise, enjoy normal sleep, perform household chores, attend social activities, drive a car, walk or have sexual relations. The effect of pain means that one in four reports that relationships with family and friends are strained or broken, according to the IASP/EFIC data. Neuropathic pain treatment is extremely difficult. Neuropathic pain is a very complex disease, involving several molecular pathways. Excitatory or inhibitory pathways controlling neuropathic pain development show altered gene expression, caused by peripheral nerve injury. Current available drugs are usually not acting on the several mechanisms underlying the generation and propagation of pain. Nowadays, pain research is directing on new molecular methods, such as gene therapy, stem cell therapy and viral vectors for delivery of biologic antinociceptive molecules. These methods could provide a new therapeutic approach to neuropathic pain relief.
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PMID:Molecular approaches for neuropathic pain treatment. 1762 16

Pain is a common complaint in the elderly patient. Chronic pain can be either nociceptive or neuropathic. Postherpetic neuralgia and painful diabetic neuropathy are two of the most common forms of neuropathic pain. Neuropathic pain can significantly affect an elderly patient's quality of life and increase use of health care resources. Several pharmacologic treatments have been shown to provide relief for neuropathic pain, including tricyclic antidepressants, anticonvulsants, tramadol, and opioids. Topical analgesics may also provide some benefit.
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PMID:All pain is not the same: an overview of neuropathic pain in the elderly. 1765 61

Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, diabetes or infection. This type of pain can be so severe that even light touching can be intensely painful. Unfortunately, this state is generally resistant to currently available treatments. There is abundant evidence that activated microglia are a key player for causing the pain and ATP receptors expressed in microglia have an important role to activate microglia. In this review, we summarize the role of microglia and ATP receptors in neuropathic pain signalling. The activated microglia express P2X4 after nerve injury, which can be stimulated by endogenous ATP, resulting in the release of BDNF which is one of key molecules involving in neuropathic pain. The microglia also express many molecules that were reported to be connected in the pain. Understanding the key roles of these ATP receptors in microglia may lead to new strategies for the management of intractable chronic pain.
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PMID:[Involvement of microglia in neuropathic pain signalling]. 1766 45

Neuropathic pain, a debilitating chronic pain following nerve damage, is a reflection of the aberrant functioning of a pathologically altered nervous system. One hallmark is abnormal pain hypersensitivity to innocuous stimuli (tactile allodynia), for which effective therapy is lacking, and the underlying mechanisms of which remain to be determined. Here we show that Lyn, a member of the Src family kinases (SFKs), plays an important role in the pathogenesis of neuropathic pain. Nerve injury, but not peripheral inflammation, increased immunoreactivity for active SFKs that were autophosphorylated in the kinase domain (phospho-SFK-IR) in spinal microglia. In spinally derived microglial cells, we identified Lyn as the predominant SFK among the five members (Src, Fyn, Yes, Lck, and Lyn) known to be expressed in the CNS. Lyn expression in the spinal cord was highly restricted to microglia, and its level was increased after nerve injury. We found that mice lacking lyn (lyn(-/-)) exhibit a striking reduction in the levels of phospho-SFK-IR and tactile allodynia after nerve injury, without any change in basal mechanical sensitivity or inflammatory pain. Importantly, lyn(-/-) mice displayed impaired upregulation of the ionotropic ATP receptor subtype P2X(4) receptors (P2X(4)R) in the spinal cord after nerve injury, which is crucial for tactile allodynia. Microglial cells from lyn(-/-) mice showed a deficit in their ability to increase P2X(4)R expression in response to fibronectin, a factor implicated as a microglial P2X(4)R upregulator in allodynia. Together, our findings suggest that Lyn may be a critical kinase mediating nerve injury-induced P2X(4)R upregulation and neuropathic pain.
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PMID:Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. 1791 63

Neuropathic pain resulting from damage to or dysfunction of peripheral nerves is not well understood and difficult to treat. Although CNS hyperexcitability is a critical component, recent findings challenge the neuron-centric view of neuropathic pain etiology and pathology. Indeed, glial cells were shown to play an active role in the initiation and maintenance of pain hypersensitivity. However, the origins of these cells and the triggers that induce their activation have yet to be elucidated. Here we show that, after peripheral nerve injury induced by a partial ligation on the sciatic nerve, in addition to activation of microglia resident to the CNS, hematogenous macrophage/monocyte infiltrate the spinal cord, proliferate, and differentiate into microglia. Signaling from chemokine monocyte chemoattractant protein-1 (MCP-1, CCL2) to its receptor CCR2 is critical in the spinal microglial activation. Indeed, intrathecal injection of MCP-1 caused activation of microglia in wild-type but not in CCR2-deficient mice. Furthermore, treatment with an MCP-1 neutralizing antibody prevented bone marrow-derived microglia (BMDM) infiltration into the spinal cord after nerve injury. In addition, using selective knock-out of CCR2 in resident microglia or BMDM, we found that, although total CCR2 knock-out mice did not develop microglial activation or mechanical allodynia, CCR2 expression in either resident microglia or BMDM is sufficient for the development of mechanical allodynia. Thus, to effectively relieve neuropathic pain, both CNS resident microglia and blood-borne macrophages need to be targeted. These findings also open the door for a novel therapeutic strategy: to take advantage of the natural ability of bone marrow-derived cells to infiltrate selectively affected CNS regions by using these cells as vehicle for targeted drug delivery to inhibit hypersensitivity and chronic pain.
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PMID:Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain. 1798 4

Neuropathic pain is caused by functional abnormalities of structural lesions or dysfunction in the peripheral or central nervous system, and occurs without peripheral nociceptor stimulation. Neuropathic pain has a great impact on the quality of life. Majority of the patients are unable to maintain an independent lifestyle due to their moderate to severe chronic pain and often depression contributes to the illness. Many common diseases, such as stroke, multiple sclerosis and syringomyelia may produce neuropathic pain. Neuropathic pain is a complex disease, involving several molecular pathways. Neuropathic pain treatment is stil extremely difficult despite our knowledge about this difficult to diagnose and treat pain condition has improved a lot with the aid of recent experimental and clinical studies. This review summarizes the underlying mechanisms, diagnosis and treatment approaches based on different mechanisms of effect.
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PMID:[Neuropathic pain]. 1809 93


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