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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 is a common and severely disabling state that affects millions of people worldwide. Such pain can be experienced after nerve injury or as part of diseases that affect peripheral nerve function, such as diabetes and AIDS; it can also be a component of pain in other conditions, such as cancer. Following peripheral nerve injury, microglia in the spinal cord become activated. Recent evidence indicates that activated microglia are key cellular intermediaries in the pathogenesis of nerve injury-induced pain hypersensitivity because P2X(4) purinoceptors and p38 mitogen-activated protein kinase, which are present in activated microglia, are required molecular mediators. It is important to establish how these molecules are activated in spinal microglia following nerve injury and how they cause signaling to neurons in the dorsal horn pain transmission network. Answers to these questions could lead to new strategies that assist in the diagnosis and management of neuropathic pain--strategies not previously anticipated by a neuron-centric view of pain plasticity in the dorsal horn.
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PMID:Neuropathic pain and spinal microglia: a big problem from molecules in "small" glia. 1566 33

Neuropathic pain resulting from nerve injury or from diseases such as diabetes, HIV AIDS or cancer, that damage the peripheral nerves, can be agonizing, persistent over long periods, and, unfortunately, is often resistant to known pain-killers. The P2X receptors, of which seven subtypes (P2X1-P2X7) have been cloned, are a family of ligand-gated cation channels activated by extracellular ATP and have important roles in regulating neuronal and glial functions in the nervous system. Recent advances in our understanding of the mechanisms underlying neuropathic pain have been made by defining important roles of P2X4 receptors and spinal microglia in the pathogenesis of neuropathic pain. Within the spinal dorsal horn, peripheral nerve injury leads to a progressive series of changes in microglia including morphological hypertrophy of the cell body and proliferation that are considered indicative of activation. Furthermore, P2X4 receptors that which are upregulated in activated microglia, have been found to be essential molecular mediators. The activation of P2X4 receptors releases brain-derived neurotrophic factor from microglia; this mediates the signaling from microglia to neurons, which in turn leads to pain hypersensitivity. We expect that understanding the key roles of these molecules in spinal microglia may lead to new strategies for the management of neuropathic pain.
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PMID:[Neuropathic pain and ATP receptors in spinal microglia]. 1788 77

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 that typically develops when peripheral nerves are damaged through surgery, bone compression in cancer, diabetes, or infection is a major factor causing impaired quality of life in millions of people worldwide. Recently, there has been a rapidly growing body of evidence indicating that spinal glia play a critical role in the pathogenesis of neuropathic pain. Accumulating findings also indicate that nucleotides play an important role in neuron-glia communication through P2 purinoceptors. Damaged neurons release or leak nucleotides including ATP and UTP to stimulate microglia through P2 purinoceptors expressing on microglia. It was shown in an animal model of neuropathic pain that microglial P2X(4) and P2X(7) receptors are crucial in pain signaling after peripheral nerve lesion. In this review, we describe the modification of neuropathic pain sensation through microglial P2X(4) and P2X(7), with the possibility of P2Y(6) and P2Y(12) involvement.
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PMID:Modification of neuropathic pain sensation through microglial ATP receptors. 1840 44

There is abundant evidence that extracellular ATP and other nucleotides have an important role in pain signaling at both the periphery and in the CNS. At first, it was thought that ATP was simply involved in acute pain, since ATP is released from damaged cells and excites directly primary sensory neurons by activating their receptors. However, neither blocking P2X/Y receptors pharmacologically nor suppressing the expression of P2X/Y receptors molecularly in sensory neurons or in the spinal cord had an effect on acute physiological pain. The focus of attention now is on the possibility that endogenous ATP and its receptor system might be activated in pathological pain states, particularly in neuropathic pain. 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. An important advance in our understanding of the mechanisms involved in neuropathic pain has been made by a recent work demonstrating the crucial role of ATP receptors (i.e., P2X(3) and P2X(4) receptors). In this review, we summarize the role of ATP receptors, particularly the P2X(4) receptor, in neuropathic pain. The expression of P2X(4) receptors in the spinal cord is enhanced in spinal microglia after peripheral nerve injury, and blocking pharmacologically and suppressing molecularly P2X(4) receptors produce a reduction of the neuropathic pain behaviour. Understanding the key roles of ATP receptors including P2X(4) receptors may lead to new strategies for the management of neuropathic pain.
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PMID:ATP receptors in pain sensation: Involvement of spinal microglia and P2X(4) receptors. 1840 95

Neuropathic pain is the most difficult type of pain to treat. The P2X(3) receptors play a crucial role in facilitating pain transmission at peripheral and spinal sites. The present research investigated the effects of tetramethylpyrazine (TMP) on the primary afferent transmission induced by P2X(3) receptor in neuropathic pain states. Chronic constriction injury (CCI) model was adopted. Sprague-Dawley male rats (n=30) had been randomly divided into normal saline (sham+NS) group (I), TMP group (II), sham group (III), CCI+TMP group (IV), and CCI group (V). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured and P2X(3) immunoreactivity in L4/L5 dorsal root ganglion (DRG) and spinal cord was detected by immunohistochemistry. The mechanical withdrawal threshold and thermal withdrawal latency in group V were lower than those in groups I-III or IV (p<0.05), while P2X(3) receptor expression of L4/L5 DRG and spinal cord in group V was higher than those in groups I-III (p<0.01) or group IV (p<0.05). The mechanical withdrawal threshold, thermal withdrawal latency and P2X(3) immunoreactivity of L4/L5 DRG and spinal cord in group IV showed no significant difference compared with those in groups I, II or III (p>0.05). The amplitudes of the currents in group V (CCI) were much larger than those obtained in other groups after application of same concentration adenosine 5'-triphosphate disodium (ATP) (p<0.01). alpha,beta-Methylene-ATP (alpha,beta-meATP)-activated currents in DRG neurons of CCI rats were more obvious than those obtained in other group rats (p<0.01). The results showed that TMP may inhibit the primary afferent transmission of neuropathic pain induced by P2X(3) receptor.
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PMID:Effect of tetramethylpyrazine on primary afferent transmission mediated by P2X3 receptor in neuropathic pain states. 1863 42

Neuropathic pain usually is persistent and no effective treatment. ATP plays an important role in the initiation of pain. P2X(3) receptors are localized in the dorsal root ganglion (DRG) neurons and activated by extracellular ATP. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the nociceptive facilitation of the primary sensory afferent after chronic constriction injury (CCI) mediated by P2X(3) receptor. In this study, the content of ATP in DRG neurons was measured by high-performance liquid chromatography (HPLC). P2X(3) agonist-activated currents in DRG neurons was recorded by the whole-cell patch-clamp skill. The expression of P2X(3) mRNA in DRG neurons was analyzed by in situ hybridization. The ATP content of DRG was increased after CCI. In CCI rats treated with SF, the content of ATP in DRG neurons was reduced. SF decreased the increment of P2X(3) agonist-activated currents and P2X(3) mRNA expression in DRG neurons during CCI. SF may inhibit the initiation of pain and primary afferent sensitization mediated by P2X(3) receptor during CCI.
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PMID:Role of sodium ferulate in the nociceptive sensory facilitation of neuropathic pain injury mediated by P2X(3) receptor. 1880 51

Neuropathic pain, a highly debilitating pain condition that commonly occurs after nerve damage, is a reflection of the aberrant excitability of dorsal horn neurons. This pathologically altered neurotransmission requires a communication with spinal microglia activated by nerve injury. However, how normal resting microglia become activated remains unknown. Here we show that in naive animals spinal microglia express a receptor for the cytokine IFN-gamma (IFN-gammaR) in a cell-type-specific manner and that stimulating this receptor converts microglia into activated cells and produces a long-lasting pain hypersensitivity evoked by innocuous stimuli (tactile allodynia, a hallmark symptom of neuropathic pain). Conversely, ablating IFN-gammaR severely impairs nerve injury-evoked microglia activation and tactile allodynia without affecting microglia in the contralateral dorsal horn or basal pain sensitivity. We also find that IFN-gamma-stimulated spinal microglia show up-regulation of Lyn tyrosine kinase and purinergic P2X(4) receptor, crucial events for neuropathic pain, and genetic approaches provide evidence linking these events to IFN-gammaR-dependent microglial and behavioral alterations. These results suggest that IFN-gammaR is a key element in the molecular machinery through which resting spinal microglia transform into an activated state that drives neuropathic pain.
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PMID:IFN-gamma receptor signaling mediates spinal microglia activation driving neuropathic pain. 1938 Jul 17

Neuropathic pain is usually persistent and there is no effective treatment. Activation of P2X(3) receptor subtype in primary sensory neurons is involved in neuropathic pain. Sodium ferulate (SF) is an active principle from Chinese herbal medicine and has anti-inflammatory activities. This study observed the effects of SF on the hyperalgesia mediated by P2X(3) receptor of rats after chronic constriction injury (CCI). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured and the expression of P2X(3) receptor immunoreactivity and protein in dorsal root ganglion (DRG) neurons was analyzed by immunohistochemistry and western blotting. In CCI rats treated with SF, the MWT and TWL were increased compared with CCI rats treated with normal saline. The expression of P2X(3) receptor in DRG neurons was increased after CCI. In CCI rats treated with SF, the up-regulated expression of P2X(3) receptor in DRG neurons was reduced. SF may reduce the thermal and mechanical hyperalgesia in CCI rat model by decreasing the pain transmitted by primary afferant neurons mediated by P2X(3) receptor during the chronic neuropathic pain injury.
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PMID:Effect of sodium ferulate on the hyperalgesia mediated by P2X3 receptor in the neuropathic pain rats. 3103 Aug 95

Neuropathic pain is the most difficult type of pain to cure. The P2X(2/3) receptors play a crucial role in facilitating the transmission of pain at neuropathic pain states. Emodin is a natural anthraquinone in rhubarb. The present research investigated the effects of emodin on the pain transmission in neuropathic pain states that was mediated by P2X(2/3) receptor in primary sensory neurons. Chronic constriction injury (CCI) model was used as neuropathic pain model. Emodin was dissolved in 0.5% sodium carboxymethyl cellulose (CMC) as vehicle. Sprague-Dawley male rats had been randomly divided into Sham+vehicle group, CCI+emodin group, and CCI+vehicle group. Mechanical withdrawal threshold and thermal withdrawal latency were measured. P2X(2/3) expression in L4/L5 dorsal root ganglion (DRG) was detected by immunohistochemistry, in situ hybridization (ISH) and RT-PCR. The mechanical withdrawal threshold and thermal withdrawal latency in CCI+vehicle group were lower than those in Sham+vehicle group and CCI+emodin group (p<0.05), while P2X(2) and P2X(3) receptor expression of L4/L5 DRG in CCI+vehicle group was higher than those in the other two groups (p<0.05). The co-local staining of P2X(2) and P2X(3) in the DRG of CCI group appeared to be more intense than that in the DRG of the other two groups with double-label fluorescence immunohistochemistry. The results showed that the application of emodin alleviated the hyperalgesia of CCI rats and significantly decreased the P2X(2/3) expression of L4/L5 DRG in CCI+emodin group compared with that in CCI+vehicle group (p<0.05). The data of ISH and RT-PCR in P2X(2) and P2X(3) mRNA expression suggest that the pharmacologic mechanism of emodin is involved in the nucleic acid level. The results showed that emodin can inhibit the transmission of neuropathic pain mediated by P2X(2/3) receptor of primary sensory neurons to alleviate chronic neuropathic pain.
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PMID:Effect of emodin on neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons. 2130 87


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