Analgesic effects of N-acetylmuramyl-L-alanyl-D-isoglutamine in decreasing the acetic acid-induced abdominal-writhing response

Ogawa, Tomohiko; Kotani, Shozo

doi:10.1128/iai.55.2.494-496.1987

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…3). On the other hand, Ogawa and Kotani 15 reported that intraperitoneal injection of MDP did not show analgesic activity at 8 h. Although the reason for the apparent discrepancies between their and our data is not clear at present, the administration route of the compound might be important. The FK565 was effective via various administration routes, not only the usual systemic routes, such as intravenous, intraperitoneal, intramuscular, and subcutaneous, but also oral routes, such as intragigival, sublingual and intragastric (Fig.…”

Section: Discussioncontrasting

confidence: 97%

“…They also reported that the minimum active entity of desmuramylpeptide was g-D-glutamyl-meso-DAP, 14 which was later reported to be the minimum structure for NOD-agonist and was designated iE-DAP. 8 In 1987, Ogawa and Kotani 15 reported that MDP and its analogs exhibited analgesic effects that decreased abdominal writhing movements induced by intraperitoneal injection of acetic acid. Horák and Mašek 16 also reported that MDP and its analog, adamantylamide dipeptide, exhibited analgesic effects.…”

Section: Introductionmentioning

confidence: 99%

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Analgesic effects of chemically synthesized NOD1 and NOD2 agonists in mice

et al. 2010

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Intracellular nucleotide-binding oligomerization domain (NOD)-like receptors, NOD1 and NOD2, recognize the diaminopimelic acid (DAP)-containing peptide moiety and muramyldipeptide (MDP) moiety of bacterial peptidoglycan, respectively. Muramyldipeptide has been reported to exert analgesic activity to decrease the frequency of acetic acid-induced writhing movements in mice. In this study, we demonstrated the analgesic activities of NOD1 as well as NOD2 agonists. Intravenous injection of NOD2-agonistic MDP, 6-O-stearoyl-MDP (L18-MDP), and MDP-Lys (L18) exhibited analgesic activity at 10, 50, and 2.0 µg/head, respectively, in BALB/c mice. NOD1-Agonistic FK156 (D-lactyl-L-Ala-D-Glu-meso-DAP-L-Gly) and FK565 (heptanoyl-D-Glu-meso-DAP-D-Ala) were also analgesic at 50 µg/head and 1.0 µg/head, respectively. The analgesic effect of FK565 appeared from 30 min, reached maximum activity at 8 h, and continued until 24 h. The FK565 exhibited activity by various administration routes; intravenous, intraperitoneal, intramuscular, sublingual (1.0 µg/head each), subcutaneous, intragastric (oral), intragingival (10 µg/ head each) and intracerebroventricular (0.01 µg/head). The analgesic activity of FK565 was observed even in tumor necrosis factor (TNF)-α knockout, interleukin (IL)-1α/β double knockout, and their triple knockout mice. Naloxane, a non-selective antagonist for the opioid receptor, completely inhibited the analgesic effect of FK565. These findings suggest that NOD1 and NOD2 activation induces an analgesic effect via opioid receptors in a TNF-α and IL-1α/β independent manner.

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Section: Discussioncontrasting

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Analgesic effects of chemically synthesized NOD1 and NOD2 agonists in mice

et al. 2010

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“…In contrast, the irritating sensation produced by weak acids, such as acetic acid, is likely mediated by sensory neurons with cell bodies in the trigeminal ganglion (TG) and whose processes terminate in the nasal and oral cavity (Brand, 2006). Consistent with activation of nociceptors, exposure to acetic acid at concentrations as low as 10 ppm produces a feeling of irritation in humans (Ernstgård et al, 2006), and in rats intraperitoneal injection of acetic acid produces a writhing that has been the basis for screening of putative analgesic agents (Ogawa and Kotani, 1987). Direct responses of nociceptors to weak acids have been measured using nerve recording, which showed increases in activity in response to a variety of acids, including carbonic acid, formed when CO 2 is dissolved, and propanoic acid (also called propionic acid [PA]), a food preservative (Silver and Moulton, 1982).…”

Section: Introductionmentioning

confidence: 99%

A TRPA1-dependent mechanism for the pungent sensation of weak acids

Wang

Chang

Allgood

et al. 2011

Journal of General Physiology

109

112

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Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been identified for many noxious chemicals, the mechanisms by which animals detect weak acids, such as acetic acid, are less well understood. Weak acids are only partially dissociated at neutral pH and, as such, some can cross the cell membrane, acidifying the cell cytosol. The nociceptor ion channel TRPA1 is activated by CO2, through gating of the channel by intracellular protons, making it a candidate to more generally mediate sensory responses to weak acids. To test this possibility, we measured responses to weak acids from heterologously expressed TRPA1 channels and trigeminal neurons with patch clamp recording and Ca2+ microfluorometry. Our results show that heterologously expressed TRPA1 currents can be induced by a series of weak organic acids, including acetic, propionic, formic, and lactic acid, but not by strong acids. Notably, the degree of channel activation was predicted by the degree of intracellular acidification produced by each acid, suggesting that intracellular protons are the proximate stimulus that gates the channel. Responses to weak acids produced a Ca2+-independent inactivation that precluded further activation by weak acids or reactive chemicals, whereas preactivation by reactive electrophiles sensitized TRPA1 channels to weak acids. Importantly, responses of trigeminal neurons to weak acids were highly overrepresented in the subpopulation of TRPA1-expressing neurons and were severely reduced in neurons from TRPA1 knockout mice. We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to cellular acidosis.

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“…The antinociceptive activity of the samples was evaluated using acetic acid induced writhing in mice [ 15 – 18 ]. In this method, acetic acid was administered intraperitoneally (i.p.)…”

Section: Methodsmentioning

confidence: 99%

Antinociceptive principle from Curcuma aeruginosa

Hossain

Al‐Amin

Sayem

et al. 2015

BMC Complement Altern Med

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BackgroundThe rhizome of Curcuma aeruginosa Roxb (Zingiberaceae) has been used as a traditional folk medicine for the treatment of rheumatic disorders in Bangladesh. The aim of the current study was the bioassay-guided isolation and purification of an antinociceptive principle from the methanol extract of C. aeruginosa rhizomes.MethodsThe antinociceptive activity was determined using acetic acid induced writhing and formalin induced licking in the Swiss albino mice to investigate central and peripheral antinociceptive principle of C. aeruginosa rhizomes. Vacuum Liquid Chromatography (VLC) and open column chromatography were used for separation. Crystallization was used for the purification of the isolated compound germacrone (1). Diclofenac (10 mg/kg) and aspirin (100 mg/kg) were used as positive control and 5 % carboxymethyl cellulose (CMC) in distilled water (10 ml/kg) for negative control were used in the acetic acid induced writhing and formalin induced licking methods.ResultsThe methanol extract exhibited 37.50 and 45.31 % inhibition of writhing; 33.27 and 38.13 % inhibition of licking in the first phase and 69.72, 73.71 % inhibition of licking in the second phase at doses of 200 and 400 mg/kg, respectively. VLC of the extract yielded five fractions (Fr. 1 to Fr. 5). Fr. 1 exhibited 33.98 % inhibition that was comparably higher than other fractions (Fr. 2 to Fr. 5) at a dose of 100 mg/kg. Column chromatography of Fr. 1 generated five fractions (SF. 1 to SF. 5). Fraction SF.3 exhibited 46.88 % inhibition that was most potent among the other fractions at a dose of 50 mg/kg. Crystallization of the fraction SF.3 yielded germacrone (1), a cyclic sesquiterpene. Germacrone (1) showed 22.66, 34.77 and 51.17 % inhibition of writhing at doses of 10, 20 and 40 mg/kg, respectively; 30.43 and 37.53 % inhibition in the initial phase and 32.27 and 60.96 % inhibition in the second phase of licking at doses of 200 and 400 mg/kg, respectively.ConclusionGermacrone (1) showed a potent activity in both writhing and licking methods that indicates the compound as a central and peripheral antinociceptive principle of C. aeruginosa rhizomes with possible anti-inflammatory activity.

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Analgesic effects of N-acetylmuramyl-L-alanyl-D-isoglutamine in decreasing the acetic acid-induced abdominal-writhing response

Cited by 7 publications

References 12 publications

Analgesic effects of chemically synthesized NOD1 and NOD2 agonists in mice

Analgesic effects of chemically synthesized NOD1 and NOD2 agonists in mice

A TRPA1-dependent mechanism for the pungent sensation of weak acids

Antinociceptive principle from Curcuma aeruginosa

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