Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analgesia has been reported to be facilitated by supraspinal nitric oxide (NO) and cyclic guanosine monophosphate (cGMP). In the rostromedial medulla, an important pain-suppressing region, iontophoretically delivered 8-bromo-cGMP excited most single recorded cells (9/10), and methylene blue (a guanylyl cyclase inhibitor) inhibited all cells (7/7). Nitrite and ferrous ions together, shown voltammetrically ex vivo to yield nitric oxide (NO), excited some cells (14/28) and inhibited others (7/28). Methylene blue blocked excitation (3/3) but not inhibition (4/4) by the putative NO. Spontaneous or glutamate-evoked firing was gradually inhibited (23/32) or unaffected by N omega-nitro-L-arginine (a NO synthase inhibitor), but was mostly inhibited by L-arginine (the NO precursor) (23/26), although a rapid onset militated against elevated NO production. These substances, excepting L-arginine, produced changes consistent with an excitatory cGMP-NO cascade contributing to analgesia.
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PMID:Excitation of cells in the rostral medial medulla of the rat by the nitric oxide-cyclic guanosine monophosphate messenger system. 858 98

In the present study the role of L-arginine/nitric oxide (NO)/cGMP pathway in the antinociceptive activity of pyridoxine in p-benzoquinone-induced abdominal constriction test in mouse was investigated. Pyridoxine (CAS 58-56-0) displayed dose-dependent antinociceptive activity at 0.0625-1 mg/kg (s.c.) doses. L-arginine (CAS 1119-34-2), a NO precursor, displayed a triphasic pattern as antinociception-nociception-antinociception (61.8 +/- 7.8, -36.5 +/- 12.7 and 17.0 +/- 4.3%, 5, 40 and 50 mg/kg, s.c., respectively). The antinociceptive effect of pyridoxine at ED50 dose (0.43 mg/kg, s.c.) (47.7 +/- 3.9%) was significantly decreased by L-arginine at 40 and 50 mg/kg doses (4.1 +/- 9.3 and 37.8 +/- 1.6%, respectively) while 5 mg/kg dose of L-arginine significantly potentiated the pyridoxine analgesia. On the other hand, pyridoxine reversed the L-arginine-induced nociception to antinociception (4.1 +/- 9.3%) and augmented the antinociceptive effect of L-arginine (37.8 +/- 1.6%). L-NG-nitroarginine methyl ester (CAS 51298-62-5), a NO synthase inhibitor, at 75 mg/kg, s.c. produced antinociception and significantly increased the antinociceptive effect of pyridoxine (63.7 +/- 1.2%). Methylene blue (CAS 61-73-4, MB), a guanylyl cyclase and/or NO synthase inhibitor, was antinociceptive and nociceptive at 5 and 40 mg/kg doses, respectively, 5 mg/kg dose of MB significantly increased the antinociceptive effect of pyridoxine, but did not change it at 40 mg/kg dose. On the other hand, pyridoxine significantly decreased the antinociceptive effect of MB and reversed the MB-induced nociception to antinociception. Combination of pyridoxine and morphine (CAS 57-27-2) (ED50: 0.13 mg/kg, s.c.) at 49.8 +/- 1.9% revealed a significant antinociceptive potentiation (69.1 +/- 1.8%). The findings of the present study emphasise the contribution of central and/or peripheral L-arginine/NO/cGMP nociceptive processes in pyridoxine-induced antinociception.
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PMID:The role of L-arginine/nitric oxide pathway in the antinociceptive activity of pyridoxine in mouse. 1171 36

Lactoferrin (LF) is a multifunctional protein that is widely found in milk, blood, and other biological fluids. In the present study, we investigated the possibility that LF may block a tolerance to morphine-induced analgesia in the mouse. The nociceptive effect of bovine milk-derived LF (bLF) was estimated in the mouse tail-flick test. Although an intraperitoneal (100 mg/kg) or an oral (300 mg/kg) administration of bLF did not show remarkable analgesia, a combination with intraperitoneal administration of morphine (3 mg/kg) strikingly enhanced morphine-induced analgesia. Moreover, repeated administration of morphine at doses of 3 mg/kg (ip) or 5 mg/kg (ip) caused a tolerance to the morphine on the 5th or 7th day, respectively. In contrast, the combination of bLF (100 mg/kg, ip) with morphine (3 mg/kg, ip) retarded the development of tolerance to the 9th day, although bLF did not show any effect on the mice that had obtained tolerance to morphine. Furthermore, the potentiative effect of bLF was partially blocked by pre-treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and completely blocked by 7-nitroindazole (7-NI), a selective neuronal NOS (nNOS) inhibitor. Methylene blue (MB), a guanylate cyclase (GC) inhibitor, also dose-dependently prevented the potentiative effect of bLF. These results suggest that bLF selectively activates nNOS and then accelerates NO production. The increased NO in turn modulates the GC activity and finally enhances the endogenous opioid system via cyclic guanosine monophosphate production. We conclude that bLF may block the development of tolerance to morphine in mice, possibly via the selective activation of nNOS.
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PMID:Milk-derived lactoferrin may block tolerance to morphine analgesia. 1638 99