Acetic acid-induced writhing test

A number of in vivo pharmacological studies reported that amino acid substitution in position 6 of 14-O-methyloxymorphone (48) afforded derivatives 55-60 that produce potent antinociceptive actions via peripheral mechanisms after s.c. administration in different pain models such as acute nociception i.e. tail-flick test [68], inflammatory pain i.e. formalin test [68] and carrageenan-induced hindpaw inflammation [75] and visceral pain i.e. acetic acid-induced writhing test [93]. In the tail-flick test in the rat, the 6-amino acid derivatives were 19- to 209-fold more potent than morphine (Table 7) and showed similar potency to fentanyl after s.c... 

In azabicyclo[3,3,l]non-6-ene series some compounds showed analgetic activity in the acetic acid induced writhing test.145... 

Acetic acid-induced writhing test Acetic acid is administered intraperitoneally to the test animals and the nnmber of writhings is registered. 

The antinociceptive effects of N. sativa (black cumin, Ranunculaceae) oil and its major component thymoquinone were investigated by Abdel-Fattah et al. (2000). After oral administration of doses ranging from 50 to 400 mg/kg the nociceptive response was suppressed in the hot-plate test, tail-pinch test, acetic acid-induced writhing test, and in the early phase of formalin test. There was also an inhibition of nociceptive response in the late phase of the formalin test after systemic administration and i.p. injection of thymoquinone. The s.c. injection of naloxone (1 mg/kg) significantly blocked the antinociceptive effect of N. sativa oil and thymoquinone in the early phase of the formalin test. In N. sativa oil- and thymoquinone-tolerant mice the antinociceptive effect of morphine was significantly reduced, but not vice versa. These findings indicate that N. sativa oil as weU as thymoquinone induce an antinociceptive effect by means of an indirect activation of pi- and p-opioid receptor subtypes. 

The EO from the leaves of Cymbopogon citratus (lemongrass, Poaceae) showed in the acetic acid-induced writhing test a strong inhibition dose dependently. Also in the formalin test the EO could cause an inhibition especially in the second phase of the test (100% at 200 mg/kg i.p.). Otherwise the opioid antagonist naloxone reversed the central antinociception, suggesting that the EO of Cymbopogon citratus plays a role in central and peripheral levels (Viana et al., 2000). 

The antinociceptive effect of Satureja hortensis L. (summer savory, Lamiaceae) extracts and EO, a medicinal plant used in Iranian folk medicine as stomachic, muscle, and bone pain deliver was assessed by Hajhashemi et al. (2002). The hydroalcoholic extract as well as the polyphenolic fraction and EO of the aerial parts of the herb were screened for their antinociceptive activity in the light tail-flick test, as well as in the formalin and also in the acetic acid-induced writhing test. While... 

In another study the antinociceptive effects of Teucrium polium L., a wild-growing Iranian plant belonging to the Lamiaceae, were investigated by Abdollahi et al. (2003). The total extract and the EO significantly inhibited pain-related behavior in the acetic acid-induced writhing test compared to the control. 

Lino et al. (2005) used the EO of Ocimum micranthum Willd. (Lamiaceae) from Northeastern Brazil to study its antinociceptive activity in the hot plate and in the acetic acid-induced writhing test. Upon administration of low doses the EO could inhibit the number of writhings up to 79%. The antinociceptive effect was not influenced by pretreatment with naloxone. In the formalin test pawlicking time decreased to 61%. Also in this case the pretreatment with naloxone could not reverse the antinociceptive effect, confirming that there is no involvement of the opioid system. However, an involvement of the NO system was suggested because of the reverse of the antinociception by L-arginine in the second phase of the formalin test. 

Finally, also the antinociceptive and anti-inflammatory effects of the EO from Eremanthus erythropappus (Asteraceae) leaves were reported by a Brazilian author group. The EO proved to be significantly antinociceptive in the acetic acid-induced writhing test in mice, as well in the formalin test, and also in both phases of the paw-licking test, and in the hot-plate test. The exudate volume after intrapleural injection of carrageenan was significantly reduced as well as the leukocyte mobilization by administration of this oil 4 h before the start of the study (Sousa et al., 2008). 

In addition to its effects on cell growth, CLP elicits antinociceptive and anti-inflammatory activities. Peripheral antinociceptive activity was investigated by acetic acid-induced writhing model. CLP (0.1-100 mcM/kg) inhibited acetic acid-induced abdominal constrictions dose dependently (1C50 = 0.0945). Central antinociceptive activity of CLP was demonstrated in the hot plate test. CLP (100 mcM/kg, p.o.) increased latency time 90, 120, and 150 min after treatment. Similarly, CLP caused an inhibition of nociception in formalin test. Anti-inflammatory activity of CLP was evaluated in capsaicin-induced ear edema and carrageenan-induced peripheral inflammation tests. Following oral administration at a dose of 100 mcM/kg, CLP inhibited capsaicin-induced ear edema by 55.8% and reduced leukocyte migration to the inflammatory sites by 48.3% [61]. 

Analgesic on writhing test (acetic acid-induced pain in mice) [60]... 

The compounds 25a-c and 33a-f were tested for analgesic activity [ 14] by oral administration in mice in terms of the inhibition of the writhing syndrome induced by acetic acid. The ED50 which represents the dose producing 50% inhibition of the writhing induced by acetic acid was determined. The ED50 values of the compounds tested are summarized in Table 4. The pyrazolones 25a-c showed more potent analgesic activity than 1 and amino-pyrine. 

A pain reaction is induced in mice or rats by intraperitoneal injection of an irritant (e.g. acetic acid, phenylquinone, acetylcholine). This induces stretching movements called writhings. The number of writhings, counted during time intervals of 20-30 min, represents pain intensity and is dose-dependently reduced by analgesics. This test detects almost all types of analgesics but is sensitive to unspecific effects such as sedation (Hendershot and Forsaith, J. Pharmacol. Exp. Ther. 1959, 125, 237-240). 

The writhing test was used to determine chemical-induced visceral pain sensitivity. Mice were injected with acetic acid (0.1 ml/kg of 0.8% acetic acid) and the number of writhes with or without pretreatment with kava resin (200 mg/kg po) or aqueous kava extract (200 mg/kg ip) was recorded. The number of pain-dependant reactions per minute was significantly (P < 0.001) reduced, from 22.9 to 11.3 with kava resin and from 22.7 to 3.2 with aqueous kava, indicating a pronounced analgesic effect with both preparations. The authors also raised the possibility that the muscle-relaxant and sedative effects of the extracts might have influenced the analgesic and local anesthetic actions could not be excluded (Jamieson and Duffield, 1990a). 

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