Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cortisol response to surgery was studied in two groups of children one to eight years old during the first 24 hours after lower abdominal or peripheral surgery. The children were randomly allocated to a control (C) group (n = 6) or an epidural (E) group (n = 7). In Group C, surgery was performed under general anaesthesia and postoperative pain relief was achieved by using non-narcotic analgesics only. In Group E, lumbar epidural anaesthesia was combined with light general anaesthesia and postoperative pain relief was achieved by intermittent doses of bupivacaine administered through an epidural catheter. Cortisol levels were assessed before surgery (C), at the end of surgery (H0), at the 3rd, 6th, 12th and 24th postoperative hours (H3, H6, H12, H24). In Group C, cortisol levels increased significantly at H0, H3 and H6, whereas in Group E, a significant decrease was observed at H0 and a significant increase at H12. Mean cortisol values at H0 and H24 were significantly lower in Group E, when compared with those measured in Group C. In Group E, all postoperative cortisol values remained within the normal range, despite the low level of sensory blockade achieved. This suggests that minimal doses of epidural bupivacaine are effective in decreasing the endocrine stress response to surgery in children. This could be of clinical relevance in high-risk children with poor nutritional status. In Group C, the cortisol response remained altered for a longer period of time.
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PMID:Effect of lumbar epidural anaesthesia on plasma cortisol levels in children. 334 51

We performed a randomized double-blind controlled study in community medical practice comparing lysine acetylsalicylate (LAS) and paracetamol (PAR). Both drugs were given at the same dose (1 g, thrice daily) during two days; from the third to the seventh day, the patients could freely take the same drug if necessary. The analgesic effect of drugs was measured by two means: an analog scale of pain during day 1 & 2 and the count of drugs units taken during days 3 to 7. The side effects were reported. We included 473 patients (167 men, 306 women) by means of a group of 54 general practitioners. 470 patients were stratified according to the site of pain: head (n = 113), joints (n = 80), back (n = 193), thorax (n = 11), teeth (n = 48), ENT (n = 25). The pain was either acute (73%) or chronic (27%) and scored an average +/- SD of 76 +/- 12 mm on an analog visual scale from 0 to 100 mm. Response was defined as a decrease of at least 50% of the pain score. Before intake of active drugs, all patients were given placebo. Only 14% responded. Under LAS or PAR, although the difference is not statistically significant, the number of responders was slightly higher with LAS than with PAR. Moreover, the study yields some interesting differences. During day 1 and day 2, the patients of the LAS group had less pain than those of the PAR group. This difference became statistically significant at D2 H12 (p < 0.05). LAS was significantly more effective than PAR in patients with back pain (p < 0.01), and there was a trend in favor of LAS in dental and ENT pain, and for intense pain. PAR never yielded better response levels than LAS. Among the placebo-unresponsive patients, the amount of drug taken from day 3 to day 7 was significantly lower in the LAS group than in the PAR group (p < 0.05). The side effects were comparable in both groups. According to the investigators' point of view both drugs were similarly well accepted by the patients (89.3% in LAS group, 94% in PAR group). The fact that LAS seems more effective than PAR in some kinds of pain is to bring near to the anti-inflammatory action of LAS and to its better bioavailability.
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PMID:[Comparative trial of lysine acetylsalicylate and paracetamol on pain in daily medical practice]. 895 56

Continuous peripheral nerve blocks (CPNB) after pediatric major orthopedic surgery are not widely used. We conducted a prospective descriptive study to evaluate the effectiveness of disposable elastomeric pumps for CPNB in children. After inducing general anesthesia, 25 consecutive children scheduled for major orthopedic surgery received a 0.5-mL/kg bolus of a mixture of 1% lidocaine with epinephrine and 0.25% bupivacaine in axillary, femoral, or popliteal catheters. After surgery, disposable pumps with 0.2% ropivacaine were connected. Pump flows were adjusted to the patient's weight. Postoperative pain was evaluated using a visual analog scale or Children and Infants Postoperative Pain Scale scores at H1, H6, H12, H24, and H48, as well as amounts of rescue analgesia, adverse events, and motor and sensory block. An ambulation score for the children was also evaluated. Eleven popliteal, nine femoral, and five axillary continuous blocks were performed. All the blocks were effective for surgery. The mean total dose consumption of 0.2% ropivacaine was 10.1 mg/kg. Disposable pump flow varied from -9.61% to +8.6% compared with the theoretical one. Postoperative analgesia was excellent. The median of pain score was zero at each period studied. Sensory and motor block were noted at H1 and decreased from the sixth hour. No adverse events were noted. We concluded that the use of elastomeric disposable pumps for CPNB in children was an effective technique.
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PMID:Perioperative continuous peripheral nerve blocks with disposable infusion pumps in children: a prospective descriptive study. 1293 85

Following spinal cord injury (SCI), neuropathic, chronic pain is a major cause of disability. Recently, glial P2X4 receptor (P2X4R) has been identified as a major contributor to the development of neuropathic pain after peripheral nerve injury. Here we report analysis of P2X4R expression following rat SCI. Significant lesional accumulation of P2X4R+ cells was detected as early as 24 h after SCI, reaching maximum cell numbers on Day 7. Thereafter cell numbers declined but persisted at significantly elevated, sub-maximal levels (>70%) until 1 month post injury. Double-immunolabeling identified the majority of lesional P2X4R+ cells as activated microglia/macrophages and surviving neurons/neurites. Increase of P2X4R+, beta-APP+ hypertrophic neurites correlated with proximity to the lesion. Further, P2X4R+ cells coexpressed the intracellular regulators of signalling cascades, COX-1 (>20%), COX-2 (>5%), RhoA (>60%) and RhoB (>10%).
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PMID:Spinal cord injury induces early and persistent lesional P2X4 receptor expression. 1588 21

Gabapentin is currently used as a therapeutic agent against epilepsy as well as neuropathic pain. In contrast to gabapentin, its derivative gabapentin-lactam has a pronounced neuroprotective activity. We have studied in cultured hippocampal neurons whether gabapentin-lactam has also neurotrophic effects. Gabapentin-lactam enhanced the formation of dendritic filopodia, which are necessary for synapse formation. It also induced a network of F-actin-containing neurites. In studies with time lapse microscopy, gabapentin-lactam increased the addition but also the elimination of new branches. Affinity precipitation assays showed that gabapentin-lactam increased the GTP binding of the small GTPases Rac and Cdc42, which facilitate branch addition. Gabapentin-lactam also activated RhoA and phosphatidylinositol 3-kinases. In neurons transfected with dominant-negative RhoA or treated with the RhoA-inactivating C3 toxin, gabapentin-lactam increased the number of dendrites and branches. In the presence of Y-27632, which inhibits Rho kinase, newly added branches induced by gabapentin-lactam were no longer eliminated so that gabapentin-lactam increased the number of branches. Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide] also prevented the gabapentin-lactam induced activation of phosphatidylinositol 3-kinases. The phosphatidylinositol 3-kinase inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride] reduced the elimination of newly added branches caused by gabapentin-lactam and thus facilitated branch formation. In contrast to gabapentin-lactam, gabapentin had no effect on dendritic filopodia or motility. The effects exerted by gabapentin-lactam on dendritic arborization may be of potential therapeutic interest.
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PMID:Gabapentin-lactam induces dendritic filopodia and motility in cultured hippocampal neurons. 1684 45

Among various machineries occurring in the experimental neuropathic pain model, there exists the loss of pain transmission through C-fiber neurons as well as the hypersensitivity through A-fibers. The current study reveals that molecular machineries underlying the latter hypersensitivity are derived from the events through LPA1 receptor and its downstream RhoA-activation following peripheral nerve injury. The loss of C-fiber responses, which are mediated by spinal substance P (SP) pain transmission was observed with the nociceptive flexor responses by intraplantar injection of SP in nerve-injured mice. The immunohistochemistry revealed that SP signal in the dorsal horn was markedly reduced in such mice. All these changes were completely abolished in LPA1-/- mice or by the pretreatment with BoNT/C3, a RhoA inhibitor. In addition, the loss of C-fiber responses and the down-regulation of spinal SP signal induced by single intrathecal LPA injection were also abolished in such treatments. All these results suggest that the loss of pain transmission through polymodal C-fiber neurons is also mediated by the LPA1 activation following nerve injury.
Mol Pain 2006 Aug 16
PMID:Loss of spinal substance P pain transmission under the condition of LPA1 receptor-mediated neuropathic pain. 1691 35

Lysophosphatidic acid (LPA) causes neuropathic pain with demyelination in sensory fibers. In dorsal root (DR) ex vivo culture, the addition of 0.1 microM LPA caused a characteristic demyelination at 24h in scanning and transmission electron microscopy analyses. Moreover, direct contact between C-fibers due to loss of partition by Schwann cell in Remak bundles was observed. LPA-induced demyelination of DR was concentration-dependent in the range between 0.01 and 1M, and was abolished by BoNT/C3 and Y-27632, a RhoA and Rho kinase inhibitor, respectively. The demyelination was equivalent between the preparations with and without dorsal root ganglion. LPA also caused a down-regulation of myelin proteins, such as myelin basic protein (MBP) and myelin protein zero (MPZ) to approximately 70% of control. All these findings suggest that the demyelination observed in the neuropathic pain due to nerve injury occurs through a direct action of LPA on Schwann cells.
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PMID:LPA-mediated demyelination in ex vivo culture of dorsal root. 1705 57

After a CNS injury in the adult mammals, axonal regeneration is very limited because of the reduced intrinsic growth capacity and nonpermissive environment for axonal elongation. The growth inhibitions from CNS myelin and astroglial chondroitin sulfate proteoglycans partially account for the lack of CNS repair. Here, we show that the nonsteroidal antiinflammatory drugs (NSAIDs) ibuprofen and indomethacin, the drugs widely used as pain relievers in the clinic, can surmount axon growth restrictions from myelin and proteoglycans by potently inhibiting their downstream pathway RhoA signal. Similar to Rho and Rock inhibitors C3 transferase or Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide], both NSAID drugs stimulate a significant neurite growth in the cultured dorsal root ganglion neurons exposed to the inhibitory substrates. Systemic administration of ibuprofen to spinal cord-lesioned rodents reverses the active RhoA signal around injury area measured via Rho-GTP binding assay. Subcutaneous injections of ibuprofen via minipumps to rats with a thoracic spinal cord transection or contusion injury result in substantial corticospinal and serotonergic axon sprouting in the caudal spinal cord and promote locomotor functional recovery, even delaying the treatment 1 week after trauma. In contrast, the non-RhoA-inhibiting NSAID naproxen does not have the axon growth-promoting effects on cultured or lesioned neurons. These studies demonstrate the therapeutic potential of RhoA-inhibiting NSAIDs in treating CNS injuries characterized by axonal disconnection including spinal cord injury.
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PMID:Nonsteroidal anti-inflammatory drugs promote axon regeneration via RhoA inhibition. 1742 93

Isoprenylation is crucial for the biological activation of small molecular G proteins. Activation of Rho/Rho kinase (ROCK) signaling has been reported to be involved in the initiation and maintenance of hyperalgesia caused by nerve injury and inflammation. The present study was then undertaken to examine whether the protein isoprenylation could affect thermal nociceptive threshold in the mouse spinal cord. Intrathecal administration of mevalonate (0.05-5.0 micromol) dose-dependently decreased the paw-withdrawal latencies for the thermal stimulation, indicating that mevalonate induces thermal hyperalgesia. Intrathecal pretreatment with a geranylgeranyl transferase I inhibitor GGTI-2133 (0.001-1.0 nmol) or a ROCK inhibitor Y27632 (0.001-1.0 nmol) completely blocked the mevalonate-induced thermal hyperalgesia. On the other hand, mevalonate-induced thermal hyperalgesia was only slightly attenuated by a farnesyl transferase inhibitor FTI-277 (0.01-1.0 nmol). Intrathecal injection of mevalonate increased the amount of geranylgeranylated RhoA in the spinal cord, which was completely blocked by intrathecal pretreatment with GGTI-2133. Intrathecal injection of mevalonate also produced RhoA translocation from cytosol to plasma membrane. This mevalonate-induced RhoA translocation was also blocked by intrathecal pretreatment with GGTI-2133, indicating that the RhoA translocation is triggered by RhoA geranylgeranylation. Moreover, inhibition of mevalonate synthesis by HMG-CoA reductase inhibition with simvastatin attenuated the second phase, but not the first phase, of nociceptive response to formalin. Our present results suggest that mevalonate sensitizes the spinal nociceptive transmission, which is mediated by the activation of ROCK following the RhoA geranylgeranylation.
Pain 2008 Feb
PMID:Mevalonate sensitizes the nociceptive transmission in the mouse spinal cord. 1776 39

The aim of the present study was to investigate the role of protein kinases within the spinal cord in the development of a neuropathic pain-like state induced by partial sciatic nerve ligation in mice. Thermal hyperalgesia induced by nerve ligation in mice was markedly suppressed by either repeated intrathecal (i.t.) pre-treatment or post-treatment with the selective protein kinase (PKC) inhibitor RO-32-0432 and the selective Rho kinase inhibitor Y-27632. In contrast, sciatic nerve ligation-induced thermal hyperalgesia was not observed by repeated i.t. pre-treatment with the selective PKA inhibitor KT5720. Interestingly, thermal hyperalgesia induced by nerve ligation in mice was significantly suppressed by repeated i.t. post-treatment with fasudil, which possesses the inhibitory effect of several protein kinases including PKC and Rho kinase. Collectively, these findings suggest that a long-lasting activation of PKC and RhoA/Rho kinase pathways in the spinal cord may be responsible for the development of thermal hyperalgesia induced by nerve ligation in mice. The present data raise the fascinating possibility that i.t. or epidural administration with fasudil may be useful for the treatment of neuropathic pain.
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PMID:[Effects of fasudil on neuropathic pain-like state in mice]. 1787 93


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