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

1. We examine some of the mechanisms underlying the analgesic effects of the hydroalcoholic extracts (HE) of Phyllanthus urinaria and P. niruri against formalin-induced nociception in mice. In addition, we also investigate the action of both HEs against capsaicin-mediated pain. 2. Both prazosin and yohimbine (0.15 mg/kg, i.p.) induced a marked inhibition of the analgesic effect caused by phenylephrine (10 mg/kg, i.p.) and clonidine (0.1 mg/kg, i.p.), respectively, but had no effect on the antinociceptive action caused by HE of P. urinaria (10 mg/kg, i.p.) or P. niruri (30 mg/kg, i.p.). 3. NG-nitro-L-arginine (L-NOARG, 75 mg/kg, i.p.) caused marked analgesic effect against the second phase of formalin-induced pain. Treatment of animals with L-arginine (600 mg/kg) completely antagonized the antinociceptive effect of L-NOARG but had no significant effect against the HE of P. urinaria (10 mg/kg, i.p.) or P. niruri (30 mg/kg. i.p.) analgesic properties. 4. The antinociceptive effects caused by the HEs of P. urinaria (10 mg/kg, i.p.) and P. niruri (30 mg/kg, i.p.) were unaffected by methysergide (5 mg/kg, i.p.), p-chloro-phenylalanine-methyl-ester (100 mg/kg, i.p., once a day for 4 consecutive days) or after previous adrenalectomy of animals. 5. The HE of P. urinaria and P. niruri given either intraperitoneally (1-30 mg/kg) or orally (25-200 mg/kg) caused marked and dose-related inhibition of capsaicin-induced pain with ID50 of 2.1 and 6.1 mg/kg given intraperitoneally and 39 and 35 mg/kg given orally, respectively.
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PMID:Analysis of the mechanisms underlying the antinociceptive effect of the extracts of plants from the genus Phyllanthus. 869 Feb 36

Nitric oxide (NO) donors such as sodium nitroprusside (SNP, 0.01-1 micrograms) or 3-morpholino-sydnonimine (SIN-1, 0.1-10 micrograms) administered intracerebroventricularly (i.c.v) produced a dose-dependent potentiation of beta-endorphin-induced antinociception assessed by the tail-flick test in ICR mice. The same i.c.v. treatment with SNP or SIN-1 did not affect the antinociception induced by mu-, delta-, or kappa-opioid receptor agonists. The goal of the present study was to determine if the potentiation of the beta-endorphin-induced antinociception by NO donors is mediated by the activation of NO-cGMP system. Co-administration of hemoglobin (30-120 micrograms) or methylene blue (1.25-5 micrograms), but not N omega-nitro-L-arginine (1-5 micrograms) given i.c.v. dose-dependently attenuated the potentiating effects of SNP or SIN-1 on beta-endorphin-induced antinociception. However, the same i.c.v. treatments of mice with hemoglobin, methylene blue or N omega-nitro-L-arginine did not directly affect the i.c.v. administered beta-endorphin-induced antinociception. On the other hand, the treatment of mice with a combination of NO donor (SNP, 0.1 micrograms or SIN-1, 1 microgram) and zaprinast (a cGMP phosphodiesterase inhibitor, 1 microgram) further potentiated beta-endorphin-induced antinociception. These results indicate that the potentiating effect of SNP or SIN-1 on beta-endorphin-induced antinociception is mediated by the increased production of NO-cyclic GMP in the brain. However, the NO-cGMP system is not directly involved in the beta-endorphin-induced antinociception.
Pain 1995 Dec
PMID:Activation of a NO-cyclic GMP system by NO donors potentiates beta-endorphin-induced antinociception in the mouse. 871 39

The possible participation of nitric oxide (NO) in pain modulation and stress analgesia was studied in adult Wistar rats. Cerebral citruline as a coproduct of NO from L-arginine increased from the mean value 5.6 +/- 0.4 nM/mg.Pt. to 8.9 +/- 0.5 nM/mg.Pt. in acute restraint stress. In high doses (50 mg/kg body weight), intraperitoneal administration of L-arginine caused a small and transient decrease of the tail-flick latencies to the thermal stimulus, without significant changes of the stress analgesia induced by restraint stress. In animals pretreated with N-nitro-L-arginine methyl ester (NAME) a progressive increase of the latency time was obtained and the increased latencies induced by acute immobilization appeared significantly potentiated. These results offer new indirect evidence in favour of the modulatory role of NO in thermoalgesic sensitivity and stress-induced analgesia.
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PMID:Possible involvement of the L-arginine-nitric oxide pathway in the modulation of stress-induced analgesia. 874 43

This study tested the ability of a nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), to attenuate behavioral hyperalgesia in a rat model of neuropathic pain [Bennett, G.J. and Xie, Y.-K., Pain, 33 (1988) 87-107]. A mononeuropathy was produced by chronic constriction injury (CCI) of the sciatic nerve. Thermal hyperalgesia was assessed by a reduction of paw withdrawal latency to a noxious heat source. Following CCI, there was significant hyperalgesia in groups of rats treated with D-NAME (n = 7), an inactive isomer of L-NAME, saline (n = 7) or systemic L-NAME (n = 10). In contrast, when L-NAME was applied directly and continuously to the site of CCI (5.0 micrograms/microliter per h for up to 2 weeks) via an osmotic pump implanted at the time of the injury, no significant thermal hyperalgesia was observed (n = 8). The results suggest the involvement of nitric oxide in the development and maintenance of thermal hyperalgesia in a rat model of neuropathy. The blockade of nitric oxide production at the site of injury may provide a new approach for treatment of neuropathic pain.
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PMID:Application of nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on injured nerve attenuates neuropathy-induced thermal hyperalgesia in rats. 878 89

The effects of L-NG-nitro arginine methyl ester (L-NAME), L-NG-monomethyl arginine (L-NMMA), L-arginine and D-NG-nitro arginine methyl ester (D-NAME) on morphine antinociception were studied in the mouse using two nociceptive assays, the abdominal constriction and tail flick tests. In the abdominal constriction test, L-arginine and D-NAME (20 mg/kg) had no effect on the number of abdominal constrictions, nor did they affect the responses due to morphine (1 mg/kg). L-NAME and L-NMMA (10 mg/kg) exhibited marked antinociception when administered on their own, and morphine antinociception was enhanced in mice pretreated with these two agents. In the tail flick test, similar doses of L-NAME, L-NMMA, L-arginine and D-NAME had no effect on their own. D-NAME had no effect on morphine analgesia, L-NAME and L-NMMA enhanced morphine antinociception, and L-arginine attenuated morphine antinociception. Therefore, increasing the levels of NO attenuates morphine antinociception, while lowering the levels enhances it. These results suggest that NO may play an important role in pain perception, and probably in the antinociceptive responses to morphine.
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PMID:Effects L-NG-nitro arginine methyl ester (L-NAME), L-NG-monomethyl arginine (L-NMMA) and L-arginine on the antinociceptive effects of morphine in mice. 878 70

We recently reported that intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice induced allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli. In the present study, we examined the effect of the PGE receptor EP1 subtype antagonist ONO-NT-012, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the allodynia. The PGE2-induced allodynia was blocked by simultaneous i.t. injection of ONO-NT-012, MK-801, or L-NAME. However, 5 min after i.t. injection of PGE2, the allodynia was significantly blocked by i.t. L-NAME, but not by i.t. ONO-NT-012 or MK-801. These results demonstrate that the PGE2-induced allodynia, once developed, does not require the continued agonist occupancy of EP1 and NMDA glutamate receptor sites.
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PMID:L-NAME, an inhibitor of nitric oxide synthase, blocks the established allodynia induced by intrathecal administration of prostaglandin E2. 878 49

The involvement of nitric oxide in nociceptive processing was examined at the main loci of synaptic transmission within the rat somatosensory pathway from the caudal sural cutaneous nerve. Intrathecal (lumbar 1-3) administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (30 micrograms), inhibited nitric oxide synthase in this region of the spinal cord by greater than 80% but had no significant effect on nitric oxide synthase in parietal cerebral cortex, thalamus or medulla/pons. In a rat model of peripheral neuropathy (one to two week ligation of the caudal sural cutaneous nerve), intrathecal administration of the same dose of N omega-nitro-L-arginine methyl ester prevented the hyperalgesic response to thermal stimuli. Administration of 30 micrograms N omega-nitro-L-arginine methyl ester into the lateral ventricle had no effect on nitric oxide synthase in the lumbar 1-3 region of the spinal cord but gave substantial inhibition in higher areas of the somatosensory pathway (parietal cerebral cortex, thalamus and medulla/pons). Nitric oxide synthase in the parietal cerebral cortex (but not thalamus) was inhibited to a greater extent in the hemisphere ipsilateral to the site of administration. Administration of 30 micrograms N omega-nitro-L-arginine methyl ester into the lateral ventricle decreased thermal hyperalgesia, but only when N omega-nitro-L-arginine methyl ester was administered contralateral to the ligated caudal sural cutaneous nerve and therefore ipsilateral to the cortical nociceptive processing from this nerve. Intrathecal and intracerebroventricular administration of the selective inhibitor of nitric oxide-sensitive guanylyl cyclase, 1-H-[1,2,4]oxadiazalo[4,3-a]quinoxalin-1-one, also decreased the hyperalgesic response to thermal stimuli. These data demonstrate that, in a model of neuropathic pain, nitric oxide is involved in nociceptive processing at spinal and cerebrocortical synaptic loci of the somatosensory pathway and that its actions appear to be mediated through guanylyl cyclase.
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PMID:The nitric oxide-cyclic GMP pathway is required for nociceptive signalling at specific loci within the somatosensory pathway. 880 86

A 46-year-old housewife had complaints of insidiously progressive muscle weakness and paresthesia in the distal lower limbs. On neurological examination, a slight to moderate degree of muscle weakness with slight atrophy was observed in the bilateral intrinsic hand muscles. A severe degree of muscle weakness with moderate atrophy was observed in tibialis anterior, gastrocnemius and soleus muscles. Muscle stretch reflexes were decreased in the upper limbs and absent in the lower limbs, without pathologic reflexes. She had a steppage gait. Vibratory sensation was slightly decreased in the hands and moderately decreased in the feet. Touch, pain and temperature sensations were also moderately decreased only in the feet. On laboratory examination, glycosuria (5.6g/dl) was noted. Fasting blood sugar was 226mg/dl with an elevated hemoglobin A1C level (12.7%). The right median motor and sensory nerve conduction velocities were 14.8 and 20.3 m/sec, respectively, with a markedly prolonged distal latency. No muscle action potential was obtained from stimulation of the right tibial nerve. Also, no nerve action potential was elicited from stimulation of the right sural nerve. A fascicular biopsy of the right sural nerve revealed the presence of both demyelinated and remyelinated axons, and an onion-bulb formation with a marked decrease in the density of the myelinated fibers. Based on the neurological examination and nerve conduction studies of the family members, a younger sister, younger brother and an elder daughter of the proband were found to be affected by demyelinating polyneuropathy. Diabetes mellitus was not found among the family members with laboratory evidences of demyelinating polyneuropathy. Based on the family history, an uncle on the mother's side of the proband, the proband's grandmother and a younger daughter of a proband's brother were considered to be affected. The uncle and grandmother had diabetes mellitus. Therefore, we concluded that this family had HMSN type I with autosomal dominant inheritance. In the studies on fluorescence in situ hybridization, and restriction fragment length polymorphism of the genomic DNA of the proband, a DNA duplication in the 17p11.2-12 region was not observed. However, the direct sequencing analysis of DNA fragments from genomic DNA encoding the Po gene of the proband revealed a substitution of histidine for arginine at the codon 98 in the extramembranous domain of Po. She was heterozygous for the mutant allele and normal allele. Alterations in the tertiary structure of the extramembranous domain of Po may result in an impairment of the peripheral myelin compaction. This is the second Japanese family with the same mutation (Arg98-->His) of myelin Po as reported previously by us, and this type of case is rare in the literature. Therefore, the mutation at the codon 98 may play a critical role in the development of the myelin abnormality in HMSN type IB.
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PMID:[A family of hereditary motor and sensory neuropathy type I with a mutation (Arg98-->His) in myelin Po--report on a second Japanese family]. 885 8

The effects of caffeine and nitric oxide synthesis inhibition on the antinociceptive action of ketorolac were assessed using the pain-induced functional impairment model in the rat. Nociception was induced by the intra-articular injection of uric acid. Ketorolac, but not caffeine, produced an antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of this potentiation. The results suggest the participation of the L-arginine-nitric oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced antinociception.
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PMID:Effect of caffeine coadministration and of nitric oxide synthesis inhibition on the antinociceptive action of ketorolac. 885 98

In humans, both nitric oxide (NO) and bradykinin, a naturally occurring algetic and a potent NO liberator, evoke pain from hand veins. The afferent innervation of these veins consists solely of polymodal nociceptors which are located close to the endothelium, a well-known source of NO, thus suggesting NO as a chemical link in nociception. Consistent with this hypothesis, our observations show that neither bradykinin, nor hyperosmolar solutions (a noxious physicochemical stimulus) evoke pain from hand vein segments that have been exposed to the NO-synthase (NOS) inhibitor NG-mono-methyl-L-arginine. An intact NOS pathway is therefore a prerequisite for pain to be evoked by bradykinin and hyperosmolar solutions from veins, indicating for the first time in humans that vascular pain is mediated by NO. Thus, new directions for research on analgesics may be opened.
Pain 1996 Jan
PMID:Nitric oxide as a chemical link in the generation of pain from veins in humans. 886 56


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