Abstract
Combination of two or more analgesics is widely used for the treatment of moderate and severe pain syndromes, allowing usage of lower doses of each compound and thereby limiting side effects; there is currently a large interest in investigating the potential advantages of combinations between opioids and non-steroidal inflammatory drugs (NSAIDs), coxibs in particular. The rat orofacial formalin test is a useful pre-clinical model of inflammatory trigeminal pain for evaluating antinociceptive activity of analgesics and their combinations. Injection of formalin in the rat wiskerpad induces a stereotyped response (rubbing), consisting of two distinct phases: a first 'phasic' phase and a second 'tonic' phase. In this work we tested a partial agonist to μ-opioid receptors, buprenorphine, and a selective cyclo-oxygenase-2 inhibitor, lumiracoxib, each of which given i.p. either alone or in combination. Buprenorphine reduced nociception both in the first and in the second phase, whereas lumiracoxib induced antinociception in the second phase only. The interaction between the two drugs was assessed through isobolographic analysis after combined administration at a fixed dose ratio. Such combination produced a dose-dependent antinociceptive effect in both phases. We observed a statistical difference between the theoretical and the experimental ED50, which indicated synergistic interaction in the second phase. Concerning the first phase, we assumed that the antinociceptive effects were almost completely to be attributed to buprenorphine, since lumiracoxib was ineffective when administered alone. However, we found an unexpected difference between the theoretical and experimental ED50, suggesting synergism in the first phase as well.
| Original language | English |
|---|---|
| Pages (from-to) | 57-62 |
| Number of pages | 6 |
| Journal | European Journal of Pharmacology |
| Volume | 605 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - Mar 1 2009 |
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Keywords
- Buprenorphine
- Formalin
- Isobolographic analysis
- Lumiracoxib
- Rat orofacial test
ASJC Scopus subject areas
- Pharmacology
Cite this
Antinociceptive activity of buprenorphine and lumiracoxib in the rat orofacial formalin test : A combination analysis study. / Capuano, Alessandro; De Corato, Alice; Treglia, Mariangela; Tringali, Giuseppe; Dello Russo, Cinzia; Navarra, Pierluigi.
In: European Journal of Pharmacology, Vol. 605, No. 1-3, 01.03.2009, p. 57-62.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antinociceptive activity of buprenorphine and lumiracoxib in the rat orofacial formalin test
T2 - A combination analysis study
AU - Capuano, Alessandro
AU - De Corato, Alice
AU - Treglia, Mariangela
AU - Tringali, Giuseppe
AU - Dello Russo, Cinzia
AU - Navarra, Pierluigi
PY - 2009/3/1
Y1 - 2009/3/1
N2 - Combination of two or more analgesics is widely used for the treatment of moderate and severe pain syndromes, allowing usage of lower doses of each compound and thereby limiting side effects; there is currently a large interest in investigating the potential advantages of combinations between opioids and non-steroidal inflammatory drugs (NSAIDs), coxibs in particular. The rat orofacial formalin test is a useful pre-clinical model of inflammatory trigeminal pain for evaluating antinociceptive activity of analgesics and their combinations. Injection of formalin in the rat wiskerpad induces a stereotyped response (rubbing), consisting of two distinct phases: a first 'phasic' phase and a second 'tonic' phase. In this work we tested a partial agonist to μ-opioid receptors, buprenorphine, and a selective cyclo-oxygenase-2 inhibitor, lumiracoxib, each of which given i.p. either alone or in combination. Buprenorphine reduced nociception both in the first and in the second phase, whereas lumiracoxib induced antinociception in the second phase only. The interaction between the two drugs was assessed through isobolographic analysis after combined administration at a fixed dose ratio. Such combination produced a dose-dependent antinociceptive effect in both phases. We observed a statistical difference between the theoretical and the experimental ED50, which indicated synergistic interaction in the second phase. Concerning the first phase, we assumed that the antinociceptive effects were almost completely to be attributed to buprenorphine, since lumiracoxib was ineffective when administered alone. However, we found an unexpected difference between the theoretical and experimental ED50, suggesting synergism in the first phase as well.
AB - Combination of two or more analgesics is widely used for the treatment of moderate and severe pain syndromes, allowing usage of lower doses of each compound and thereby limiting side effects; there is currently a large interest in investigating the potential advantages of combinations between opioids and non-steroidal inflammatory drugs (NSAIDs), coxibs in particular. The rat orofacial formalin test is a useful pre-clinical model of inflammatory trigeminal pain for evaluating antinociceptive activity of analgesics and their combinations. Injection of formalin in the rat wiskerpad induces a stereotyped response (rubbing), consisting of two distinct phases: a first 'phasic' phase and a second 'tonic' phase. In this work we tested a partial agonist to μ-opioid receptors, buprenorphine, and a selective cyclo-oxygenase-2 inhibitor, lumiracoxib, each of which given i.p. either alone or in combination. Buprenorphine reduced nociception both in the first and in the second phase, whereas lumiracoxib induced antinociception in the second phase only. The interaction between the two drugs was assessed through isobolographic analysis after combined administration at a fixed dose ratio. Such combination produced a dose-dependent antinociceptive effect in both phases. We observed a statistical difference between the theoretical and the experimental ED50, which indicated synergistic interaction in the second phase. Concerning the first phase, we assumed that the antinociceptive effects were almost completely to be attributed to buprenorphine, since lumiracoxib was ineffective when administered alone. However, we found an unexpected difference between the theoretical and experimental ED50, suggesting synergism in the first phase as well.
KW - Buprenorphine
KW - Formalin
KW - Isobolographic analysis
KW - Lumiracoxib
KW - Rat orofacial test
UR - http://www.scopus.com/inward/record.url?scp=60349083541&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=60349083541&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2008.12.029
DO - 10.1016/j.ejphar.2008.12.029
M3 - Article
C2 - 19168053
AN - SCOPUS:60349083541
VL - 605
SP - 57
EP - 62
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-3
ER -