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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Degenerative change in cervical segments C5-C7 was documented to determine whether osteo-ligamentous adaptations were age-related. In addition, companion morphological studies were carried out to determine whether parallel changes occurred in related soft tissues, including DRG. Independent of the provoking stimulus, aberrant soft tissue change may be expected with segmental degeneration. Two associations were identified: between the incidence of segmental degeneration and severity of DRG distortion, and between segmental degeneration and DRG inflammatory mast cell density. Peripheral type C cells seemed more susceptible to compression in circumstances of DRG distortion. In light of neuropeptide expression in these cell types, predominant type C cell compression may be clinically relevant in the noxious cascade contributing to the sensation of pain.
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PMID:Segmental degeneration in the cervical spine and associated changes in dorsal root ganglia. 1530 Aug 66

This overview reports on first experience with German DRGs version 1.0 from 2003, with special regard to relevant procedures and diagnoses of anaesthesiology. Basically, the G-DRGs are a translation of the AR-DRGs 4.1. Only the 2004 version represents a first "real" German DRG system. Particularly anaesthesiological measures for procedures which are normally performed without narcosis can lead to essentially relevant remuneration. In intensive care medicine, the hours of artificial ventilation must be recorded exactly. In the 2004 version of the G-DRGs, intensive medical performances are mainly differentiated regarding the time of ventilation, which leads to better payment than under version 1.0. In intensive care medicine, additional remuneration is only intended for dialyses and other organ-supporting procedures. Pain therapy is insufficiently documented in the G-DRGs. Although new codes of pain treatment are included in the G-DRGs, they do not lead to relevant remuneration. Diagnoses and procedures coded by the anaesthetist should be registered in the clinic information system without delay. Only non-anaesthesia-associated diagnoses, i.e. additional diagnoses resulting from the preanaesthetic check-up of the patient in the preanaesthetic department, should be checked by non-anaesthesiological physicians. The correct documentation and transfer of ASA classifications is necessary for additional charges in external quality management and to avoid financial sanctions. In our experience, regarding operated patients, anaesthetists can contribute a lot to enquiries by health insurance companies, e.g. whether the payment code for an in- or an out-patient should be used. Departments of anaesthesia should appoint an anaesthetist as DRG representative to supervise anaesthesiological coding and DRG-relevant procedures.
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PMID:[What is anaesthesiology worth in the German DRGs?--First experience with German DRGs]. 1531 60

Platelet-activating factor (PAF) is a potent inflammatory lipid mediator in peripheral tissues. However, its role in mediation of nociception in central nervous system is unknown. In the present study, whether PAF plays some role in pain transduction in the spinal cord was studied in mice. Intrathecal injection of PAF induced tactile pain, tactile allodynia at as low as 10 fg to 1 pg with a peak response at 100 fg, while lyso-PAF was without effect in the range of doses. Tactile allodynia induced by PAF was blocked by a PAF receptor antagonists, TCV-309, WEB 2086 and BN 50739. The expression of PAF receptor mRNA by RT-PCR was observed in DRG and spinal cord in mice. ATP P2X receptor antagonists, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid and 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5-triphosphate, NMDA receptor antagonist, MK 801 and nitric oxide synthetase inhibitor, 7-nitroindazole blocked the PAF-induced tactile allodynia. PAF-induced tactile allodynia and thermal hyperalgesia disappeared in neonatally capsaicin-treated adult mice, while tactile allodynia but not thermal hyperalgesia induced by intrathecally injected alpha,beta-methylene ATP, a P2X receptor agonist, was capsaicin-insensitive. The present study demonstrated that PAF is a potent inducer of tactile allodynia and thermal hyperalgesia at the level of the spinal cord. PAF-evoked tactile allodynia is suggested to be mediated by ATP and the following NMDA and NO cascade through capsaicin-sensitive fiber, different from exogenously injected alpha,beta-methylene ATP which is insensitive to capsaicin treatment.
Pain 2004 Oct
PMID:Development of tactile allodynia and thermal hyperalgesia by intrathecally administered platelet-activating factor in mice. 1536 79

Injury to peripheral nerves may result in severe and intractable neuropathic pain. Many efforts have been focused on the elucidation of the mechanisms of neuropathic pain. It was found here that integrin plays an important role in the induction of neuropathic pain and treatment of disintegrin is able to attenuate neuropathic pain. The rats were induced hyperalgesia by tightly ligating the L5 spinal nerve and cut just distal to the ligature on one side. Mechanical and thermal stimuli were applied in the middle dermatome of the hind paw. Epidural administration of triflavin (TFV), an arginine-glycine-aspartic acid (RGD) containing disintegrin, inhibited hyperalgesia induced by either mechanical or thermal stimulation. Immunohistochemistry showed that the sprouting of sympathetic nerves into DRG by neuropathic surgery was markedly inhibited by TFV. Beta 1 integrin mRNA of L5 DRG increased immediately 1 day after tight ligation and cut of L5 spinal nerve. However, beta 1 integrin mRNA in uninjured L4 DRG increased later on Day 3 after surgery. On the other hand, alpha-CGRP precursor mRNA decreased in ipsilateral L5 DRG but increased in L4 DRG after neuropathic surgery. Immunohistochemistry shows that beta 3 integrins of L5 as well as L4 increased in response to neuropathic surgery and administration of triflavin antagonized the increasing action. These results suggest that there is interaction between injured and uninjured neurons and the induction of neuropathic pain is related to neuronal sprouting. Disintegrin is able to inhibit neuronal sprouting and the induction of hyperalgesia induced by peripheral nerve injury and may thus be a new category of drugs to be developed for the treatment of neuropathic pain.
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PMID:Inhibition of neuropathic pain by a potent disintegrin--triflavin. 1536 8

Although the PI3K (phosphatidylinositol 3-kinase) pathway typically regulates cell growth and survival, increasing evidence indicates the involvement of this pathway in neural plasticity. It is unknown whether the PI3K pathway can mediate pain hypersensitivity. Intradermal injection of capsaicin and NGF produce heat hyperalgesia by activating their respective TRPV1 (transient receptor potential vanilloid receptor-1) and TrkA receptors on nociceptor sensory nerve terminals. We examined the activation of PI3K in primary sensory DRG neurons by these inflammatory agents and the contribution of PI3K activation to inflammatory pain. We further investigated the correlation between the PI3K and the ERK (extracellular signal-regulated protein kinase) pathway. Capsaicin and NGF induce phosphorylation of the PI3K downstream target AKT (protein kinase B), which is blocked by the PI3K inhibitors LY294002 and wortmannin, indicative of the activation of PI3K by both agents. ERK activation by capsaicin and NGF was also blocked by PI3K inhibitors. Similarly, intradermal capsaicin in rats activated PI3K and ERK in C-fiber DRG neurons and epidermal nerve fibers. Injection of PI3K or MEK (ERK kinase) inhibitors into the hindpaw attenuated capsaicin- and NGF-evoked heat hyperalgesia but did not change basal heat sensitivity. Furthermore, PI3K, but not ERK, inhibition blocked early induction of hyperalgesia. In acutely dissociated DRG neurons, the capsaicin-induced TRPV1 current was strikingly potentiated by NGF, and this potentiation was completely blocked by PI3K inhibitors and primarily suppressed by MEK inhibitors. Therefore, PI3K induces heat hyperalgesia, possibly by regulating TRPV1 activity, in an ERK-dependent manner. The PI3K pathway also appears to play a role that is distinct from ERK by regulating the early onset of inflammatory pain.
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PMID:Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization. 1538 13

Multidisciplinary pain management in pain centers can only be guaranteed if the DRG reimbursement system takes into account the multiple risk factors. The German pain associations prospectively analyzed clinical and administrative (DRG-related) data sets (n=3943) of inpatient and day care pain treatment facilities. The index diagnoses of 84% of the patient sample were grouped into nine basic DRGs. The most frequent pain procedure code was 8-918 ("multimodal pain management"). The minimal length of stay for this code set to 7 days was 17.2 days for the study sample. The DRG grouper software 2003 categorized 68.6% of the patients into PCCL 0 despite the proven complexity of risks and secondary diseases. The mean case weight in the sample was set at about 1. The pain-related data set analyzing pain severity, chronicity, and its influence on various functions emphasizes the total severity and burden of disease and thus the necessity for multimodal pain management. The German pain societies carried the motion that a new complex ICD code for chronic pain (with biopsychosocial consequences) should be established in the German Modification of the ICD. The new ICD code F62.80 and the procedure code 8-918 had not yet been implemented into the German DRG algorithm. Due to modifications in DRG systematics and the DRG algorithm, to be activated in 2005, the procedure code 8-918 will now automatically trigger into four special basic pain DRGs corresponding to the index pain diagnosis.
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PMID:[Organized pain management in the DRG reimbursement system]. 1557 32

NaV1.8 is a voltage-gated sodium channel expressed only in a subset of sensory neurons of which more than 85% are nociceptors. In order to delete genes in nociceptive neurons, we generated heterozygous transgenic mice expressing Cre recombinase under the control of the NaV1.8 promoter. Functional Cre recombinase expression replicated precisely the expression pattern of NaV1.8. Cre expression began at embryonic day 14 in small diameter neurons in dorsal root, trigeminal and nodose ganglia, but was absent in non-neuronal or CNS tissues into adulthood. Sodium channel subtypes were normal in isolated DRG neurons. Pain behaviour in response to mechanical or thermal stimuli, and in acute, inflammatory and neuropathic pain was also normal. These data demonstrate that the heterozygous NaV1.8-Cre mouse line is a useful tool to analyse the effects of deleting floxed genes on pain behaviour.
Pain 2005 Jan
PMID:Nociceptor-specific gene deletion using heterozygous NaV1.8-Cre recombinase mice. 1562 61

Vanilloid receptor 1 (TRPV1) is a Ca2+ permeable non-specific cation channel located at the peripheral nerve terminals and functions as a polymodal nociceptor. Neomycin, an aminoglycoside antibiotic induces analgesia in various animal models. However, the mechanism of action of neomycin has not been fully understood. In this study, we have determined the effect of neomycin on native TRPV1 in cultured embryonic DRG neurons and cloned TRPV1 heterologously expressed in Xenopus oocytes using patch clamp, double electrode voltage clamp, and Ca2+ fluorescence imaging techniques. Here, we show that neomycin potently (IC50 approximately 400 nM) blocks TRPV1-mediated membrane currents in DRG neurons and the block is unrelated to capsaicin concentrations used to evoke currents, suggesting a non-competitive block. Similarly, capsaicin- and proton-induced currents are blocked in oocytes, but to a lesser extent. Increases in capsaicin-induced intracellular Ca2+ levels are also reduced by neomycin. Single-channel current analyses reveal that single-channel conductance is unaffected by neomycin and there is no indication of open channel block. The predominant effect is to lower, the open probability (Po) at both, negative and positive potentials. Kinetic analyses reveal that the number of exponential components required to fit the open time distributions remains the same or reduced, however, the longest open time constant and the area of distribution are shortened at negative and positive potentials, respectively. The area of distribution of longest closed-time constants were significantly prolonged at negative and positive potentials. We conclude that neomycin inhibits TRPV1 channel activity by allosteric binding and altering channel gating.
Pain 2005 Jan
PMID:Block of native and cloned vanilloid receptor 1 (TRPV1) by aminoglycoside antibiotics. 1562 72

Activation of extracellular signal-regulated kinase (ERK), a mitogen activated-protein kinase (MAPK), in dorsal horn neurons contributes to inflammatory pain by transcription-dependent and -independent means. We have now investigated if ERK is activated in the spinal cord after a spinal nerve ligation (SNL) and if this contributes to the neuropathic pain-like behavior generated in this model. An L5 SNL induces an immediate (<10 min) but transient (<6 h) induction of phosphoERK (pERK) restricted to neurons in the superficial dorsal horn. This is followed by a widespread induction of pERK in spinal microglia that peaks between 1 and 3 days post-surgery. On Day 10, pERK is expressed both in astrocytes and microglia, but by Day 21 predominantly in astrocytes in the dorsal horn. In the L5 DRG SNL transiently induces pERK in neurons at 10 min, and in satellite cells on Day 10 and 21. Intrathecal injection of the MEK (ERK kinase) inhibitor PD98059 on Day 2, 10 or 21 reduces SNL-induced mechanical allodynia. Our results suggest that ERK activation in the dorsal horn, as well as in the DRG, mediates pain through different mechanisms operating in different cells at different times. The sequential activation of ERK in dorsal horn microglia and then in astrocytes might reflect distinct roles for these two subtypes of glia in the temporal evolution of neuropathic pain.
Pain 2005 Mar
PMID:ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. 1573 40

Ectopic discharge generated in injured afferent axons and cell somata in vivo contributes significantly to chronic neuropathic dysesthesia and pain after nerve trauma. Progress has been made toward understanding the processes responsible for this discharge using a preparation consisting of whole excised dorsal root ganglia (DRGs) with the cut nerve attached. In the in vitro preparation, however, spike activity originates in the DRG cell soma but rarely in the axon. We have now overcome this impediment to understanding the overall electrogenic processes in soma and axon, including the resulting discharge patterns, by modifying the bath medium in which recordings are made. At both sites, bursts can be triggered by subthreshold oscillations, a phasic stimulus, or spikes arising elsewhere in the neuron. In the soma, once triggered, bursts are maintained by depolarizing afterpotentials, whereas in the axon, an additional process also plays a role, delayed depolarizing potentials. This alternative process appears to be involved in "clock-like" bursting, a discharge pattern much more common in axons than somata. Ectopic spikes arise alternatively in the soma, the injured axon end (neuroma), and the region of the axonal T-junction. Discharge sequences, and even individual multiplet bursts, may be a mosaic of action potentials that originate at these alternative electrogenic sites within the neuron. Correspondingly, discharge generated at these alternative sites may interact, explaining the sometimes-complex firing patterns observed in vivo.
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PMID:Multiple interacting sites of ectopic spike electrogenesis in primary sensory neurons. 1575 67


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