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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing evidence supports a possible role for nitric oxide (NO) in the transmission of pain signals and in the development of central mechanisms of hyperalgesia. Previously, we have shown that nitroglycerin, an NO donor, is able to induce a long-lasting hyperalgesic state in rats. Nitroglycerin-induced hyperalgesia can be detected as an increase in the nociceptive behavior evoked by the formalin test. In the present study we investigated the possible mediators in the nitroglycerin-induced hyperalgesic state. Male Sprague-Dawley rats were injected with nitroglycerin and pretreated with indomethacin, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) or N(omega)-nitro-L-arginine methyl ester (L-NAME). The results obtained showed that inhibition of prostaglandins or NO synthesis prevents nitroglycerin-induced hyperalgesia in Phase II of the formalin test. A similar inhibitory effect was also observed following pretreatment with the glutamate antagonist MK801. The present findings point to the role of prostaglandins, NO synthesis and glutamate activity in the induction of nitroglycerin-induced hyperalgesia.
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PMID:Prostaglandins, glutamate and nitric oxide synthase mediate nitroglycerin-induced hyperalgesia in the formalin test. 1650 4

Activation of spinal N-methyl-D-aspartate (NMDA) receptors and then the nitric oxide and the arachidonic acid pathways is important in pain transmission. This study assessed the effects of the NMDA receptor channel blocker ketamine, the nitric oxide synthase inhibitor L-NAME, and the cyclooxygenase inhibitor ketoprofen in nociceptive transmission using an in vitro neonatal rat spinal cord preparation. Supramaximal electrical stimulation of the dorsal root evoked the A-fibre- and C-fibre-mediated high intensity excitatory postsynaptic potential (EPSP) in the ipsilateral ventral root. Low intensity stimulation evoked the A-fibre-mediated monosynaptic compound action potential (MSR) superimposed on the low intensity EPSP. Both the low intensity EPSP and the high intensity EPSP contain NMDA-receptor-mediated components. Only ketamine and ketoprofen depressed the synaptic responses. Ketamine depressed all three spinal reflexes with IC(50) values (with 95% CI) of 10.80 microM (5.97 to 19.54 microM) for the MSR, 8.29 microM (4.53 to 14.17 microM) for the low intensity EPSP, and 5.35 microM (3.05 to 9.40 microM) for the high intensity EPSP. Ketoprofen depressed the low intensity EPSP and the high intensity EPSP only; IC(50) values (with 95% CI) were 354.5 microM (217.5 to 576.8 microM) and 302.7 microM (174.0 to 526.7 microM), respectively. Reflexes recovered after drug washout. These data demonstrated that ketamine and ketoprofen, but not L-NAME, depressed NMDA-mediated nociceptive transmission in spinal cord preparations from neonatal rats.
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PMID:Depression of NMDA-receptor-mediated segmental transmission by ketamine and ketoprofen, but not L-NAME, on the in vitro neonatal rat spinal cord preparation. 1671 67

Persistent stimulation of nociceptors and C-fibers by tissue injury causes hyperalgesia and allodynia by sensitization of nociceptors and facilitation of synaptic transmission in the spinal cord. The important participant in the inflammatory response of injured peripheral nerve may be nitric oxide (NO). The aim of the present study was to test the sensitivity of PDE5 inhibitor sildenafil in chronic constriction injury (CCI) model a rat model of neuropathic pain. Sciatic nerve injury is associated with development of hyperalgesia 14 days after the nerve ligation. Sildenafil (100 and 200 microg/rat, i.t.) produced a significant decrease in pain threshold, which in lower dose did not alter the nociceptive threshold. The hyperalgesic effect of sildenafil was blocked by L-NAME and methylene blue (MB), which on per se treatment showed antinociceptive effect in nerve ligated rats. The results from the present study indicated that the major activation of NO-cGMP pathway in the chronic constriction injury model of neuropathic pain. The aggravation of hyperalgesic response might be due to the increased cGMP levels resulting in PKG-I activation and its upregulation.
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PMID:Sildenafil induces hyperalgesia via activation of the NO-cGMP pathway in the rat neuropathic pain model. 1683 9

The present study examined the acute toxicity and antinociceptive effects of diphenyl diselenide (PhSe)2, given orally (p.o.), in chemical and thermical models of pain in mice. Diphenyl diselenide (7.8-312 mg/kg, p.o.) did not cause mortality. This compound did not change plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) activities as well as urea and creatinine levels in mice after 72 h of exposure. Diphenyl diselenide (1-100 mg/kg, p.o.) inhibited acetic acid-, capsaicin-, glutamate-, bradykinin(BK)- and phorbol myristate acetate (PMA)-induced pain. Diphenyl diselenide also reduced glutamate-, bradykinin-, PMA-induced paw oedema formation. Moreover, diphenyl diselenide caused a significant increase in tail-immersion response latency time. Diphenyl diselenide co-injected subplantarly in association with glutamate-induced a significant reduction of the licking and in the paw oedema formation induced by glutamate. The local pre-treatment of mice with l-arginine, intraplantarly, restored antinociception caused by diphenyl diselenide or N(G)-nitro-L-arginine methyl ester (L-NAME) when analyzed against glutamate-induced nociception. The pre-treatment of mice with dithiothreitol (DTT) intraplantarly restored local antinociception caused by diphenyl diselenide or 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) when analyzed against glutamate-induced nociception. These results indicate that diphenyl diselenide produced antinociception in several models of pain through mechanisms that involve an interaction with not only nitrergic system but also via interaction with redox modulatory sites of glutamate receptors.
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PMID:Antinociceptive properties of diphenyl diselenide: evidences for the mechanism of action. 1712 7

Drimys angustifolia Miers. (Winteraceae) is a Brazilian medicinal plant used as analgesic, antiulcer and anti-inflammatory without studies to assure its efficacy and safety Leaf and stem bark extracts were evaluated to determine the antiulcer, analgesic, antiinflammatory and antioxidant activities. Preliminary toxic effects and qualitative phytochemical profile were also performed. The antiulcer activity was detected in both extracts. Administration of the leaf extract at 250 mg/kg inhibited total lesion area by 76.50% (p < 0.01 in ethanol/HCl method), while carbenoxolone at 250 mg/kg reduced lesions by 69.48%. Stem bark extract (250 mg/kg) inhibited lesion by 81.42%, while carbenoxolone by 74.10%. Similar effects were observed in the ethanol-induced ulcer method, but no activity was observed in piroxican model. The effects involve nitric oxide in gastric protection, since the L-NAME treatment reversed the protection given by the extracts. Antioxidant effects suggest an involvement against oxidative stress. In the pain (writhing, tail-flick and hot-plate tests) and inflammation (carrageenan-induced paw edema) models, the extracts did not present any effect. The phytochemical studies demonstrated that both extracts contain flavonoids, saponins, glycosilated triterpenoids, fixed acids, cyanogenic glycosides, quinones, tannins, xanthone and steroidal aglycones. Toxicological studies showed that the extracts are safe at the effective antiulcer doses.
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PMID:Pharmacological and toxicological studies of Drimys angustifolia Miers. (Winteraceae). 1728

Agmatine, an endogenous cationic amine resulting from the decarboxylation of L-arginine, produces antihyperalgesic and antiallodynic effects in animal models of chronic neuropathic and inflammatory pain. We examined the effect of agmatine on tactile and thermal allodynia and on mechanical hyperalgesia in streptozocin-induced diabetic rats. To determine its mechanism of action and the potential interest of some of its combinations, the antihyperalgesic effect of agmatine was challenged with alpha(2)-adrenergic imidazoline and opioid-receptor antagonists, and its interaction with the opioid-receptor agonist morphine, the competitive N-methyl-D-aspartate receptor antagonist D-CPP [R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid], and the nitric-oxide synthase inhibitor L-NAME (L-N(G)-nitro-L-arginine methyl ester) were examined. When intrathecally (i.t.) injected (4.4 to 438 nmol/rat), agmatine was ineffective in normal rats but suppressed tactile allodynia (von Frey hair test), thermal allodynia (tail immersion test), and mechanical hyperalgesia (paw-pressure test) in diabetic rats. This spinal antihyperalgesic effect was suppressed by idazoxan (40 micromol/rat i.t.) but not by yohimbine (40 micromol/rat i.t.) or naloxone (0.69 micromol/rat i.v.). In diabetic rats, an isobolographic analysis showed that combinations of i.t. agmatine with i.v. L-NAME or with i.t. morphine resulted in an additive antihyperalgesic effect, whereas the agmatine/D-CPP i.t. combination was superadditive. In summary, the present findings reveal that spinal agmatine produces antiallodynic and antihyperalgesic effects in diabetic neuropathic pain involving, at least for its antihyperalgesic effect, the imidazoline receptors. Moreover, agmatine combined with D-CPP produces an antinociceptive synergy in experimental neuropathy, opening opportunities in the development of new strategies for pain therapy.
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PMID:Agmatine induces antihyperalgesic effects in diabetic rats and a superadditive interaction with R(-)-3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid, a N-methyl-D-aspartate-receptor antagonist. 1755 Oct 93

The L-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway is known to be involved in central and peripheral nociceptive processes. This study evaluated the rhythmic pattern of the L-arginine/NO/cGMP pathway using the mouse visceral pain model. Experiments were performed at six different times (1, 5, 9, 13, 17, and 21 h after light on) per day in male mice synchronized to a 12 h:12 h light-dark cycle. Animals were injected s.c. with saline, 2 mg/kg L-arginine (a NO precursor), 75 mg/kg L-N(G)-nitroarginine methyl ester (L-NAME, a NOS inhibitor), 40 mg/kg methylene blue (a soluble guanylyl cyclase and/or NOS inhibitor), or 0.1 mg/kg sodium nitroprusside (a nonenzymatic NO donor) 15 min before counting 2.5 mg/kg (i.p.) p-benzoquinone (PBQ)-induced abdominal constrictions for 15 min. Blood samples were collected after the test, and the nitrite concentration was determined in serum samples. L-arginine or L-NAME caused both antinociception and nociception, depending on the circadian time of their injection. The analgesic effect of methylene blue or sodium nitroprusside exhibited significant biological time-dependent differences in PBQ-induced abdominal constrictions. Serum nitrite levels also displayed a significant 24 h variation in mice injected with PBQ, L-NAME, methylene blue, or sodium nitroprusside, but not saline or L-arginine. These results suggest that components of L-arginine/NO/cGMP pathway exhibit biological time-dependent effects on visceral nociceptive process.
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PMID:Twenty-four-hour variation of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway demonstrated by the mouse visceral pain model. 1761 41

The present study examined the antinociceptive effects induced by 2,3-bis(mesitylseleno)propenol, a bis-selenide alkene derivate, given orally, in chemical models of pain in rats and mice. Selenide administered orally (p.o.) into the rats caused antinociception against the first and second phases of the formalin test, with mean ID(50) values of 28.17 and 39.68 mg/kg, respectively. The antinociceptive effect caused by selenide (50 mg/kg, p.o.) on the formalin test was reversed by pretreatment with N(G)-L-nitro-arginine methyl ester (L-NAME, a nitric oxide (NO) synthase inhibitor), methylene blue (a non-specific NO/guanylyl cyclase inhibitor) and glibenclamide (an ATP-sensitive K(+) channel inhibitor), but not by atropine (a muscarinic antagonist). Given orally selenide in mice produced an inhibition of glutamate-, histamine- and compound 48/80-induced nociception with mean ID(50) values of 27.58, 36.18 and 44.53 mg/kg, respectively. Moreover, oral treatment with selenide in mice decreased licking -- induced by serotonin (mean ID(50) value of >50 mg/kg). The data show that selenide exerts pronounced systemic antinociception in chemical (formalin, glutamate, histamine, compound 48/80 and serotonin-induced pain) models of nociception. Taken together, these results suggest that the antinociceptive effect of selenide on the formalin test involves the participation of nitric oxide/cyclic GMP/K(+) channel pathways in rats.
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PMID:Role of nitric oxide/cyclic GMP/K(+) channel pathways in the antinociceptive effect caused by 2,3-bis(mesitylseleno)propenol. 1803 63

The possible involvement of the nitric oxide (NO)-cyclic GMP (cGMP)-protein kinase G (PKG) pathway on bovine lactoferrin (BLF)-induced spinal antihyperalgesic activity was elucidated in sciatic nerve injured rats. Intrathecal BLF reduced thermal hyperalgesia in a dose-dependent manner. Pretreatment with NG-L-nitro-arginine methyl ester (L-NAME, non-specific inhibitor of NO synthase), 7-nitroindazole (7-NI, neuronal NO synthase inhibitor), 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl-cyclase inhibitor), (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2, 9-dimethyl-1-oxo-9, 12-epoxy-1H-diindolo-[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor) or glybenclamide (ATP-sensitive K+ channel blocker), but not NG-D-nitro-arginine methyl ester (D-NAME, an inactive enantiomer of l-NAME), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2 (CTOP, selective mu-opioid receptor antagonist) or naloxone (nonselective opioid receptor antagonist) prevented BLF-induced antihyperalgesia. Data suggest that BLF-induced spinal antihyperalgesia could be due to activation of the NO-cGMP-PKG-K+ channel pathway and it is not mediated by mu-opioid receptor in a model of neuropathic pain.
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PMID:Involvement of the nitric oxide-cyclic GMP-protein kinase G-K+ channel pathway in the antihyperalgesic effects of bovine lactoferrin in a model of neuropathic pain. 1840

Various animal models of pain are dependent on activation of different glutamate receptor subtypes. First degree burn of the paw elicits a secondary hyperalgesia that is dependent on Ca2+ permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), but not N-methyl-D-aspartate (NMDA) receptors. The present study takes advantage of that specificity by examining the effects of spinal pretreatments of agents on this secondary hyperalgesia. Rats with indwelling intrathecal catheters were pretreated with agents prior to paw injury. Mechanical withdrawal thresholds were measured before, and for three h after the injury. Spinal pretreatment with cyclooxygenase (10 and 30 microg (S)-(+)-ibuprofen; and 3 and 30 microg ketorolac) and nitric oxide synthase (33 and 100 microg N(G) Nitro-L-arginine methyl ester hydrochloride (L-NAME) and 10 microg thiocitrulline) inhibitors resulted in no specific anti-allodynia. In contrast, ziconotide (0.3, 1.0 and 3 microg), the N-type voltage gated calcium channel antagonist was very effective in blocking burn-induced sensitivity at all doses used. l-type (Diltiazam 230 microg) and P-type (Agatoxin IVA 0.3 microg) calcium channel blockers produced intermediate effects. Thus, cyclooxygenase and nitric oxide synthase are assumed not to be downstream of Ca2+ permeable AMPA receptors. Voltage gated calcium channels blockers could exert their effects either pre- or post-synaptically.
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PMID:Secondary hyperalgesia in the rat first degree burn model is independent of spinal cyclooxygenase and nitric oxide synthase. 1844 May 3


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