Mechanism of Action of Nonsteroidal Anti-inflammatory Drugs

Yaksh, Tony L.; Dirig, David M.; Malmberg, Annika B.

doi:10.3109/07357909809011705

Cited by 74 publications

(51 citation statements)

References 122 publications

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“…In brain and spinal cord cyclooxy-Ž genase-2 is constitutively expressed McCormak, 1994;. Cashman, 1996;Yaksh et al, 1998 . Cyclooxygenase-1 and cyclooxygenase-2 are encoded Ž by different genes Yokoyama and Tanabe, 1989;Kraemer . et al, 1992 but they exhibit a 62% homology at the aminoacid level.…”

Section: Introductionmentioning

confidence: 99%

“…The antiinflammatory capacity of the different NSAIDs is now proposed to be associated with the capacity of inhibiting cyclooxygenase-2 activity. A central analgesic effect of NSAIDs Ž has also been proposed McCormak, 1994;Cashman, 1996;. Yaksh et al, 1998 , which is probably mediated by regula-Ž tion of cyclooxygenase-2 activity in the spinal cord Dirig .…”

Section: Introductionmentioning

confidence: 99%

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Regulation of cyclooxygenase activity by metamizol

Campos

Gregorio

Garcı́a-Nieto

et al. 1999

European Journal of Pharmacology

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The ability of metamizol to inhibit cyclooxygenase-1 and cyclooxygenase-2 activities has been evaluated using different cyclooxygenase sources. Metamizol inhibited purified cyclooxygenase-1 and cyclooxygenase-2 with an IC of about 150 mgrml. A similar IC 50 50value for cyclooxygenase-2 was obtained in lipopolysaccharide-activated broken murine macrophages. Consistent with these findings, molecular models of the complexes between cyclooxygenase-1 or cyclooxygenase-2 with 4-methylaminoantipyrine, the major active derivative of metamizol, suggested a common binding mode to both isoforms. In intact cells, however, the inhibition profiles were Ž . markedly different. The IC values of metamizol for cyclooxygenase-1 in intact bovine aortic endothelial cells BAEC cells and human 50 platelets were 1730 " 150 mgrml and 486 " 56 mgrml, respectively. Inhibition of cyclooxygenase-2 activity in murine macrophages and primary human leukocytes activated by lipopolysaccharide yielded IC values of 12 " 1.8 mgrml and 21 " 2.9 mgrml, 50 respectively. These data indicate that the IC values obtained with purified enzymes or disrupted cells cannot always be extrapolated to 50 Ž . the cyclooxygenase inhibitory activity of nonsteroidal antiinflammatory drugs NSAIDs in intact cells. The data presented here also indicate that cyclooxygenase-2 inhibition could play an important role in the pharmacological effects of metamizol. q 1999 Elsevier Science B.V. All rights reserved.Ž .

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regulation of cyclooxygenase activity by metamizol

Campos

Gregorio

Garcı́a-Nieto

et al. 1999

European Journal of Pharmacology

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“…1 4 The spinal effects of NSAIDs are not as well documented, but include the possibility of a non-antiinflammatory analgesic action brought about by the inhibition of cyclooxygenase in the spinal cord and a consequent reduction in spinal NMDA-mediated events. 14,15 When administered prior to injury, opioid agonists and local anesthestics prevent central sensitization by attenuating nociceptive processing and blocking nerve conduction, respectively. In contrast, the pre-emptive analgesic effects of NSAIDs arise by attenuating the inflammatory response thereby reducing peripheral sensitization and its effects on spinal nociceptive processing, including the induction and maintenance of central sensitization.…”

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confidence: 99%

Pre-emptive analgesia: importance of timing

Katz

2001

Can J Anesth/J Can Anesth

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“…28,31,32 Previous studies have demonstrated that the analgesic effects of NSAIDs have been attributed to their peripheral anti-inflammatory actions, but the spinal effects of NSAIDs are not as well documented. 10,33 Thus, compared with central neuroinflammation, peripheral immune responses to nerve injury may play a partial role in nerve-induced pain hypersensitivity. Crucial research on the adenylate cyclase inhibitor still needs to be conducted, including acquisition of doseresponse data, minimum effective dose, pharmacokinetics, bioavailability, and its ability to penetrate the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 Attempts to produce preemptive analgesia have been made with opioids, non-steroidal anti-inflammatory drugs (NSAIDs), local anesthetics, and N-methyl-D-aspartic acid receptor antagonists. [8][9][10] Other potentially beneficial agents are under investigation.…”

Section: Résumémentioning

confidence: 99%

Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats

Liou

Liu

Mao

et al. 2009

Can J Anesth/J Can Anesth

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Purpose There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model. Methods Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 lmol Á L -1 , 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed.Results Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1-3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P \ 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P \ 0.05). Conclusion Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed. RésuméObjectif Des donne´es soutiennent que la transduction de l'ade´nosine monophosphate cyclique (AMPc) est implique´e dans le traitement des signaux nociceptifs. Nous avons pre´ce´demment montre´que l'injection intrathe´cale d'un inhibiteur de l'ade´nylcyclase atte´nuait l'allodynie tactile cause´e par une ligature partielle du nerf sciatique (PSNL) chez le rat. Cette e´tude explore les effets pre´ventifs de la transduction d'AMPc rachidienne sur le traitement des signaux nociceptifs dans un mode`le de douleur neuropathique chronique. Méthode Un cathe´te´risme intrathe´cal et une PSNL ont e´te´re´alise´s sur des rats maˆles Sprague-Dawley. Les re´actions nociceptives aux stimuli me´caniques et thermiques ont e´te´e´value´es a`la patte arrie`re a`2 heures et a`3, 7 et 14 jours post-PSNL. Les effets pre´ventifs de l'inhibiteur intrathe´cal de l'ade´nylcyclase, le SQ22536, (0.7 lmolÁL -1 , 30 min avant ou apre`s la ligature du nerf) ont e´te´e´value´s. De plus, les profils d'expression spatiale et temporelle et

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Mechanism of Action of Nonsteroidal Anti-inflammatory Drugs

Cited by 74 publications

References 122 publications

Regulation of cyclooxygenase activity by metamizol

Regulation of cyclooxygenase activity by metamizol

Pre-emptive analgesia: importance of timing

Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats

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