Involvement of NO in Antinociception of NSAIDS in Murine Formalin Hind Paw Assay

Abstract

There are different animal models to evaluate pain among them the formalin hind paw assay which is widely used since some of its events appear to be similar to the clinical pain of humans. The assay in which a dilute solution of formalin is injected into the dorsal hindpaw of a murine produces two ‘phases’ of pain behavior separated by a inactive period. The early phase (Phase I) is probably due to direct activation of nociceptors and the second phase (Phase II) is due to ongoing inflammatory input and central sensitization. Mice were used to determine the potency antinociceptive of piroxicam (1,3,10,and 30 mg/kg), parecoxib (0.3, 1,3,10 and 30 mg/kg), dexketoprofen (3,10,30 and 100 mg/kg) and ketoprofen (3,10,30 and 100 mg/kg). Dose-response for each NSAIDs were created before and after 5 mg/kg of L-NAME i.p. or 5 mg/kg i.p. of 7-nitroindazole. A least-squares linear regression analysis of the log dose–response curves allowed the calculation of the dose that produced 50% of antinociception (ED50) for each drug. The ED50 demonstrated the following rank order of potency, in the phase I: piroxicam > dexketoprofen > ketoprofen > parecoxib and in the phase II: piroxicam > ketoprofen > parecoxib > dexketoprofen. Pretreatment of the mice with L-NAME or 7-nitroindazol induced a significant increase of the analgesic power of the NSAIDs, with a significant reduction of the ED50. It is suggested that NO may be involved in both phases of the trial, which means that nitric oxide regulates the bioactivity of NSAIDs.

Nitridergic Modulation of COX-2 Efficacy

“…Furthermore, the results obtained in the present study are in agreement with the analgesic activity of parecoxib in orofacial formalin test reported by Isiordia-Espinoza et al, [20] and the formalin hind paw by Noriega et al, [21]. It is necessary to specify that parecoxib, the prodrug of valdecoxib, presented significant and dose-dependent analgesia only in the second phase of the trial with formalin [22].…”

Ilex paraguariensis extract as an alternative to pain medications

“…It was demonstrated that the administration of meloxicam or dexamethasone had induced antinociceptive activity with different potentials in phases I and II of the formalin--induced orofacial test which is in agreement with other algesiometric studies (24). Meloxicam inhibits cyclooxygenase, an enzyme essential for prostaglandin production (25), which is consistent with the results found in this work where selective inhibition of COX 2 (26) was observed, suggesting prostaglandins participate already in the first stage of the pain induced by formalin.…”

Synergistic Antinociceptive Effect of β-Caryophyllene Oxide in Combination with Paracetamol, and the Corresponding Gastroprotective Activity

“…In phase I of the formalin test, neurogenic pain is caused by the direct stimulation of nociceptors. Phase II is characterized by inflammation, involving both inflammatory mechanisms and central sensitization within the dorsal horn [30][31][32].…”