Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This account will consider the events occurring in the spinal cord that give rise to acute pain. The transmission and control of acute pain is not immutable but subject to plasticity so that the dividing line between acute and chronic pain is difficult to draw. Very brief acute pain is transmitted in a simple way and rarely produces difficulties in treatment. The situation within the spinal cord changes if the stimulus continues. After only seconds of C-fibre stimulation, additional peptides are released from C fibres, and spinal N-methyl-D-aspartate (NMDA) receptor activation and nitric oxide production occur. Soon after, genes are induced in central neurones, and increases and decreases in diverse pharmacological systems involved in pain transmission and modulation occur over periods of only a few hours. This rapid plasticity has important implications for the pharmacological treatment of acute because both the level of pain transmission and pain modulation will be altering over time.
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PMID:Central acute pain mechanisms. 763 18

Our study was designed to determine involvement of nitric oxide (NO) in the antinociception mediated by mu, delta and kappa opioid receptors in acute and prolonged pain in the rat spinal cord. The effect of intrathecally (i.t.) injected NO synthase inhibitors and opioid receptor agonists was evaluated in acute pain using a tail-flick and a paw pressure tests, and in prolonged pain by quantification the pain-related behavior after peripheral formalin injection. It was found that the neuronal NO synthase inhibitor 7-nitroindazole (50-400 microg), used in inactive doses, dose-dependently enhanced antinociception induced by morphine (0.5 microg) in the tail-flick and paw pressure. Moreover, coadministration of N(G)-nitro-L-arginine methyl ester (50 microg) another NO synthase inhibitor, with morphine (0.05-0.5 microg) as well as with specific agonists of mu ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin 0.1-2.5 ng) and delta ([D-Pen(2,5)]enkephalin 0.02-0.5 microg) opioid receptors, enhanced dose-dependent antinociception in the tail-flick and paw pressure. Coadministration of N(G)-nitro-L-arginine methyl ester with specific kappa opioid receptor agonist 3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzenacetamid e (10-100 microg), produced antinociception in the paw pressure only. Additionally, N(G)-nitro-L-arginine methyl ester (100 microg) profoundly potentiated the antinociception induced by [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (0.5, 15 ng) and [D-Pen(2,5)]enkephalin (2, 10 microg) in the dose-related manner in the formalin test. N(G)-nitro-L-arginine methyl ester (100 microg) also enhanced the antinociception induced by 3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzenacetamid e (10-100 microg) but only at the last two time points of the second phase of the formalin test. These data show that inhibition of the spinal NO synthase potentiates the mu-, delta- and to a lesser extent, kappa-mediated spinal antinociception in both acute and prolonged pain.
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PMID:Inhibition of nitric oxide synthase enhances antinociception mediated by mu, delta and kappa opioid receptors in acute and prolonged pain in the rat spinal cord. 926 66

The aim of present study was to determine the influence of nitric oxide (NO) synthesis on intrathecal (i.t.) clonidine or baclofen antinociception in the formalin test. Formalin injection into the hindpaw of a rat induces a biphasic response in pain-related behaviours, such that C-fiber activation (acute pain) during phase 1 triggers a state of spinal sensitization characterized by longer lasting phase 2 (tonic pain). Intrathecal clonidine and baclofen, at doses without effect upon motor performance, produced a dose-dependent inhibition of both phases of the formalin test. Potency of both drugs, defined by ID50 for phase 2 of the formalin test, was 3.5 and 0.6 nmol, respectively. Intrathecal coadministration of L-arginine, substrate of NO synthase (NOS) or NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), dose-dependently reduced or potentiated, respectively, the antinociceptive effect of clonidine but not that of baclofen in the formalin test. The importance of NO formation in the antinociceptive effect of clonidine is further supported by the observation that neither D-arginine nor D-NAME were able to modify clonidine antinociception. These results suggest that the NO synthesis plays a modulatory role in the antinociceptive effect of clonidine, while the mechanism underlying the baclofen-induced antinociception seems to be different.
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PMID:Nitric oxide modulates spinal antinociceptive effect of clonidine but not that of baclofen in the formalin test in rats. 1008 37

Nitric oxide (NO) has been shown to be involved in the generation and processing of pain signals. Most experimental studies on animals and also the few observations in humans point to an involvement of the NO-system in inflammatory pain, whereas acute pain and chronic pain without inflammatory component seem to be independent of NO. It is yet unknown whether specific inhibition of the NO pathway is useful for treatment or prevention of inflammatory pain in humans.
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PMID:[The significance of nitric oxide in nociception and spinal pain processing]. 1141 96

The spinal analgesic effects of Kyotorphin (Kyo) and Melanocyte-inhibiting factor (MIF-l) were studied during acute pain in rats chronically implanted with intrathecal (i.t.) cannulas. Kyo (5 micrograms), t-Cav (5 micrograms), Tyr-Cav (5 micrograms), L-NAME (1500 micrograms), MIF-Cav (200-400 micrograms) and MIF-sLeu (200 micrograms) exerted antinociceptive effects in both tests. The coadministration of Kyo + L-NAME enhanced the nociceptive effect compared with L-NAME (PP) or Kyo alone (PP, TF). The combination of Tyr-Cav + L-NAME enhanced the antinociceptive effect compared with L-NAME (PP) or Tyr-Cav alone (TF, PP). MIF-l (200 micrograms) had a weak antinociceptive effect in both tests. The coadministration of MIF-Cav + L-NAME enhanced the nociceptive effect compared with L-NAME (TF) or MIF-Cav alone (TF). The combination of MIF-sLeu + L-NAME enhanced the antinociceptive effect compared with L-NAME (TF) or MIF-sLeu alone (TF, PP). The results suggest that nitric oxide (NO) is involved in the antinociceptive effects of neuropeptides in the rat spinal cord.
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PMID:Involvement of nitric oxide in the nociception of kyotorphin, TYR-CAV and MIF-s analogues in the rat spinal cord. 1273 54

COX-inhibiting nitric oxide donators (CINODs) are a new class of drugs in development for the treatment of acute and chronic pain. They comprise a COX-inhibiting moiety linked to a nitric-oxide-donating component and are designed to provide an innovative mechanism of action of balanced COX inhibition and controlled nitric oxide donation. Through these pathways, CINODs should provide analgesic and anti-inflammatory efficacy, while offering gastrointestinal safety through the tissue-protective effects of nitric oxide donation. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is the first agent in the CINOD class to enter extensive clinical development. Pre-clinical studies demonstrate that AZD3582 has a superior gastrointestinal safety profile to naproxen, while demonstrating analgesic and anti-inflammatory efficacy. In healthy human volunteers, AZD3582 caused little gastrointestinal damage compared with equimolar doses of naproxen. Studies to evaluate the longer-term gastrointestinal safety of AZD3582, alongside its efficacy in alleviating chronic and acute pain, are ongoing.
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PMID:The CINOD, AZD3582, exhibits an improved gastrointestinal safety profile compared with naproxen in healthy volunteers. 1503 97

Whereas neuroaxially administered clonidine produces analgesia partially mediated by alpha2-adrenoceptor-induced augmented synthesis of nitric oxide (NO), the central mechanisms by which clonidine produces its antinociceptive effects are still speculative. We used the tail-flick model of acute pain in mice to further explore the role of NO in mediating clonidine-induced central analgesia. Cerebroventricular administration of the following agents was studied: clonidine, L-arginine (NO precursor), the NO production inhibitor nitro-L-arginine-methyl ester (L-NAME), the NO antagonist methylene blue (MB), and nitroglycerine (NO-releasing agent). Analgesic response was achieved with clonidine and L-arginine. Simultaneous administration of L-arginine and clonidine produced no additive analgesic effect. Prior administration of L-NAME or MB partially abolished the clonidine-induced analgesic effect, whereas nitroglycerine administration did not affect it. NO may be involved in the mediation of the central antinociceptive effects of clonidine. Further investigation is necessary to determine the possible role of NO-promoting agents in analgesia when co-administered with clonidine.
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PMID:Cerebroventricular injection of clonidine causes analgesia mediated by a nitrogen pathway. 1608 56

Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.
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PMID:Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test. 1611 33

All-trans retinoic acid (ATRA), the active metabolite of vitamin A, is involved in the inflammatory reaction and modulates the expression of cyclooxygenase (COX) enzymes and nitric oxide (NO) activity. Since COX enzymes are the substrate of action of COX inhibitors, we studied the analgesic activity of paracetamol (PAR) and its NO-derivative nitroparacetamol (NOP) in the presence and absence of oral ATRA. Nociceptive responses were studied using the recording of single motor units technique in alpha-chloralose anesthetized normal and monoarthritic male Wistar rats. Intravenous PAR was not effective in normal rats. However, after pre-treatment with ATRA, PAR reduced dose-dependently the responses to noxious mechanical stimulation (ID50: 60+/-7 micromol/kg; 9.1 mg/kg), but not wind-up. The analgesic activity of NOP was enhanced after pre-treatment with ATRA either on responses to noxious mechanical stimulation (ID50s: 147+/-2 vs. 46+/-2 micromol/kg) or wind-up (maximal effect of 46+/-1% with 480 micromol/kg vs. 33+/-3% of control with 240 micromol/kg). The administration of ATRA did not modify the effect of PAR and NOP in monoarthritic rats. We conclude that pre-treatment with oral ATRA enhances the analgesic activity of PAR and NOP in acute pain, probably due to a positive modulation of their activity on spinal cord COX enzymes.
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PMID:Enhancement of the analgesic activity of paracetamol and nitroparacetamol by the oral administration of all-trans retinoic acid. 1687 Feb 15

The clinical severity of sickle-cell disease (SCD) is dependent on genetic and environmental variables. Environmental factors have been poorly studied. We have investigated possible links between air pollution and acute pain in SCD. We retrospectively studied the numbers of daily admissions with acute sickle-cell pain to King's College Hospital, London, in relation to local daily air quality measurements. We analysed 1047 admissions over 1400 d (1st January 1998-31st October 2001). Time series analysis was performed using the cross-correlation function (CCF). CCF showed a significant association between increased numbers of admissions and low levels of nitric oxide (NO), low levels of carbon monoxide (CO) and high levels of ozone (O(3)). There was no association with sulphur dioxide (SO(2)), nitrogen dioxide or PM(10) (dust). The significant results were further examined using quartile analysis. This confirmed that high levels of O(3) and low levels of CO were associated with increased numbers of hospital admissions. Low NO levels were also associated with increased admissions but did not reach statistical significance on quartile analysis. Our study suggests air quality has a significant effect on acute pain in SCD and that patients should be counselled accordingly. The potential beneficial effect of CO and NO is intriguing and requires further investigation.
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PMID:The associations between air quality and the number of hospital admissions for acute pain and sickle-cell disease in an urban environment. 1734 Dec 71


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