Synergism between COX-3 inhibitors in two animal models of pain

Muñoz, Juan Pablo; Navarro, Carlos; Noriega, Viviana; Pinardi, G.; Sierralta, Fernando; Prieto, Juan Carlos; Miranda, Hugo F.

doi:10.1007/s10787-009-0019-7

Cited by 30 publications

(26 citation statements)

References 32 publications

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“…Analgesic drug combinations are widely used in pain management in humans in order to enhance or preserve antinociception, and decrease side effects. the mechanisms responsible for the synergism in the analgesic activity of nSAiDs combinations are not clear; however, according to the published information, different systems are partially involved (70,71). the metamizole effects are potentiated by tricyclic antidepressants, oral contraceptive agents, allopurinol, B vitamins, and also alcohol (76,99).…”

Section: Potentiation Of Analgesic Effectmentioning

confidence: 99%

Metamizole: A Review Profile of a Well-Known “Forgotten” Drug. Part I: Pharmaceutical and Nonclinical Profile

Nikolova

Tencheva

Voinikov

et al. 2012

Biotechnology & Biotechnological Equipment

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Section: Potentiation Of Analgesic Effectmentioning

confidence: 99%

Metamizole: A Review Profile of a Well-Known “Forgotten” Drug. Part I: Pharmaceutical and Nonclinical Profile

Nikolova

Tencheva

Voinikov

et al. 2012

Biotechnology & Biotechnological Equipment

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“…In addition, only few analgesic trials have been undergone in trigeminal region, and a lot of difficulties in the management of acute and chronic orofacial pain conditions stem from a lack of recognition and understanding of pain mechanisms. 2,3) Thus, the management of orofacial disorders is one of the most challenging in the pharmacology field in relation to analgesics. 4) It is well recognized that sigma-1 receptors (Sig-1Rs) are widely distributed in mammalian central nervous system (CNS) including certain cortical areas, the hypothalamus and the dorsal horn of the spinal cord.…”

mentioning

confidence: 99%

Sigma-1 Receptor Antagonist, BD1047 Reduces Nociceptive Responses and Phosphorylation of p38 MAPK in Mice Orofacial Formalin Model

Roh

Yoon

2014

Biological & Pharmaceutical Bulletin

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Sigma-1 receptors (Sig-1Rs) play a role in different types of pain and in central sensitization mechanism in spinal cord. However, it is currently unexplored whether Sig-1Rs are involved in orofacial pain processing. Here we show whether a selective Sig-1R antagonist, BD1047 reduces nociceptive responses in the mouse orofacial formalin model and the number of Fos-immunoreactive (ir) cells in the trigeminal nucleus caudalis (TNC). In addition, it was examined whether the phosphorylation of extracellular signal-regulated kinase (pERK) or p38 (pp38) mitogen-activated protein kinases (MAPK), which are closely linked to pain signaling and sensitization, in TNC was modified by BD1047. The 5% formalin (10 µL) was subcutaneously injected into the right upper lip, and the rubbing responses with ipsilateral fore- or hind paw were counted for 45 min. BD1047 (1, 3 or 10 mg/kg) were intraperitoneally treated 30 min before formalin injection. High dose of BD1047 (10 mg/kg) produced significant anti-nociceptive effects in the first and the second phase. The number of Fos-ir cells in ipsilateral side of TNC was also reduced by BD1047 as compared to that in saline-treated animals. In addition, the number of pp38-ir cells in ipsilateral TNC was decreased in BD1047-treated animals, whereas the number of pERK-ir cells was not modified. Collectively, these results demonstrate that Sig-1Rs play a pivotal role in the orofacial pain processing, and the pp38 signaling pathway can be associated with Sig-1R's action in TNC.

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“…However, only few analgesic trials have been undergone in trigeminal region, and a lot of difficulties in the management of acute and chronic orofacial pain conditions stem from a lack of recognition and understanding of pain mechanisms. 2,3) In this regard, the management of orofacial disorders is one of the most challenging in the pharmacology field in relation to analgesics.It is well established that an alpha-2 adrenoceptor agonist, clonidine significantly attenuates nociception and hyperalgesia in acute and chronic pain animal models.4,5) Alpha-2 adrenoceptor agonists are thought to produce analgesia primarily by actions in the spinal cord, both by reducing the release of glutamate and substance P from central afferent terminals 6,7) and by hyperpolarizing dorsal horn neurons. 8,9) These phenomena are related to the inhibition of N-type Ca 2+ channels on the presynaptic membrane and to an increase in the conductance of inwardly rectifying potassium channels in dorsal horn neuron, respectively.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Clonidine Reduces Nociceptive Responses in Mouse Orofacial Formalin Model: Potentiation by Sigma-1 Receptor Antagonist BD1047 without Impaired Motor Coordination

Yoon

Kang

Kim

et al. 2015

Biological & Pharmaceutical Bulletin

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Although the administration of clonidine, an alpha-2 adrenoceptor agonist, significantly attenuates nociception and hyperalgesia in several pain models, clinical trials of clonidine are limited by its side effects such as drowsiness, hypotension and sedation. Recently, we determined that the sigma-1 receptor antagonist BD1047 dose-dependently reduced nociceptive responses in a mouse orofacial formalin model. Here we examined whether intraperitoneal injection of clonidine suppressed the nociceptive responses in the orofacial formalin test, and whether co-administration with BD1047 enhances lower-dose clonidine-induced antinociceptive effects without the disruption of motor coordination and blood pressure. Formalin (5%, 10 µL) was subcutaneously injected into the right upper lip, and the rubbing responses with the ipsilateral fore-or hind-paw were counted for 45 min. Clonidine (10, 30 or 100 µg/kg) was intraperitoneally administered 30 min before formalin injection. Clonidine alone dose-dependently reduced nociceptive responses in both the first and second phases. Co-localization for alpha-2A adrenoceptors and sigma-1 receptors was determined in trigeminal ganglion cells. Interestingly, the sub-effective dose of BD1047 (3 mg/kg) significantly potentiated the anti-nociceptive effect of lower-dose clonidine (10 or 30 µg/kg) in the second phase. In particular, the middle dose of clonidine (30 µg/kg) in combination with BD1047 produced an anti-nociceptive effect similar to that of the high-dose clonidine, but without a significant motor dysfunction or hypotension. In contrast, mice treated with the high dose of clonidine developed severe impairment in motor coordination and blood pressure. These data suggest that a combination of low-dose clonidine with BD1047 may be a novel and safe therapeutic strategy for orofacial pain management.Key words alpha-2 adrenoceptor; clonidine; sigma-1 receptor; orofacial pain; formalin testThe orofacial region is one of the most densely innervated, by the trigeminal nerve, areas of the body, which focuses some of the most common acute pains, i.e., those accompanying the pathological states of the teeth and the related structures.1) It is also the site of frequent chronic post-herpetic neuralgia, migraine, and referred pains. However, only few analgesic trials have been undergone in trigeminal region, and a lot of difficulties in the management of acute and chronic orofacial pain conditions stem from a lack of recognition and understanding of pain mechanisms. 2,3) In this regard, the management of orofacial disorders is one of the most challenging in the pharmacology field in relation to analgesics.It is well established that an alpha-2 adrenoceptor agonist, clonidine significantly attenuates nociception and hyperalgesia in acute and chronic pain animal models.4,5) Alpha-2 adrenoceptor agonists are thought to produce analgesia primarily by actions in the spinal cord, both by reducing the release of glutamate and substance P from central afferent terminals 6,7) and by hyperpolarizing dor...

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Synergism between COX-3 inhibitors in two animal models of pain

Cited by 30 publications

References 32 publications

Metamizole: A Review Profile of a Well-Known “Forgotten” Drug. Part I: Pharmaceutical and Nonclinical Profile

Metamizole: A Review Profile of a Well-Known “Forgotten” Drug. Part I: Pharmaceutical and Nonclinical Profile

Sigma-1 Receptor Antagonist, BD1047 Reduces Nociceptive Responses and Phosphorylation of p38 MAPK in Mice Orofacial Formalin Model

Clonidine Reduces Nociceptive Responses in Mouse Orofacial Formalin Model: Potentiation by Sigma-1 Receptor Antagonist BD1047 without Impaired Motor Coordination

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