Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients with localized superficial pain had their pain alleviated by single epidural infusion with low dose ketamine. The patients are as follows: a 62-year-old female with herpetic neuralgia on her right sixth thoracic nerve area; a 52-year-old male whose left shoulder, anterior chest and abdomen had been burned by acetylene gas; and a 49-year-old male whose bilateral hands suffering from frostbite by propane gas. Epidural tube insertion to administer a single dose of 10 mg ketamine with lidocaine or bupibacaine was performed in all the three patients. They were administered single epidural infusion of 10 mg ketamine with lidocaine or bupibacaine everyday and they continued to receive epidural block with lidocaine or bupivacaine including buprenorphine or morphine. Therefore, we suspect that single epidural infusion of ketamine, an antagonist for N-methyl-D-aspartic acid receptor, could be an effective and useful alternative treatment in patients with various refractory localized superficial pain of either acute or chronic nature.
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PMID:[Usefulness of epidural infusion of ketamine for relief of localized superficial pain]. 1145 79

We experienced a case of stump pain relieved by continuous intravenous ketamine infusion therapy. A 59-year-old male had his left first through fourth toes amputated because a giant iron plate at work fell on his left foot fifteen years ago. Thereafter he had refractory spontaneous burning pain and night pain on his stump. On examination, we found his left foot skin hard, lustrous, and with sweating disturbance, allodynia and hyperpathia. As intravenous administrations of ketamine 10 mg and thiamylal 50 mg were positive as a drug challenge test, we performed intravenous ketamine infusion at 1 mg.kg-1.hr-1 for 1 hour and a half. After this treatment, his visual analogue scale (VAS) improved dramatically to 0 mm, and night pain, allodynia and hyperpathia disappeared for three days. Thereafter stump pain was relieved to the level of VAS 20 mm. Therefore we diagnosed his stump pain as central pain of neuropathic origin. We suspect that continuous intravenous infusion of ketamine, a noncompetitive blocker of N-methyl-D-aspartic acid receptor, might be an effective and useful alternative treatment in a patient with refractory stump pain.
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PMID:[Stump pain relieved by continuous intravenous ketamine infusion therapy]. 1151 69

Four patients with postherpetic neuralgia had their pain alleviated by epidural administration of ketamine. No oral non-steroidal anti-inflammatory drugs and anti-depressant drugs were effective in all cases. Lidocaine or bupivacaine was administered epidurally to all four patients. When these patients stated that they did not feel pain reduced, they received epidural infusion of ketamine at doses from 5 mg to 20 mg with lidocaine or bupivacaine and their postherpetic neuralgia was controlled. Therefore with these cases, we suspect that epidural administration of ketamine, an antagonist for N-methyl-D-aspartic acid receptor, could be an effective and useful alternative treatment in a patient with refractory postherpetic neuralgia.
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PMID:[Usefulness of epidural administration of ketamine for relief of postherpetic neuralgia]. 1155 28

1. Magnesium (Mg)-deficient rats develop a mechanical hyperalgesia which is reversed by a N-Methyl-D-Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor-channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non-NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg-deficient rats. 2. Hyperalgesic Mg-deficient rats were administered intrathecally (10 microl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2 h. 3. Intrathecal administration of MgSO4 (1.6, 3.2, 4.8, 6.6 micromol) as well as NMDA receptor antagonists such as MK-801 (0.6, 6.0, 60 nmol), AP-5 (10.2, 40.6, 162.3 nmol) and DCKA (0.97, 9.7, 97 nmol) dose-dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2 nmol) and 7-NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150 micromol x kg(-1), i.p.) induced an anti-hyperalgesic effect in a dose-dependent manner. SR-140333 (0.15, 1.5, 15 nmol) and SR-48968 (0.17, 1.7, 17 nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold. 4. These results demonstrate that Mg-deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non-NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia.
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PMID:Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats. 1170 42

Tetanic stimuli of peripheral C fibers produces long-term potentiation (LTP) in the spinal cord, which may contribute to sensitization of spinal pain-sensitive neurons. Zn2+ is widely distributed in the central nervous system and has blocked (LTP) in the hippocampus. The present study examined the effects of Zn2+ on the induction and maintenance of C fiber-evoked LTP in the deep dorsal horn of spinalized rats in vivo. The sciatic nerve was stimulated by tetanic stimuli for inducing LTP. (1) Topical administration of Zinc chloride (15 microM) to the spinal cord 15 min before tetanic stimulation completely blocked the induction of LTP, but not the baseline C responses. When Zn2+ was given 2 h after induction of LTP, no significant effect occurred. (2) Chelation of Zn2+ by disodium calcium ethylene diaminetelraacetate (CaEDTA) (500 microM) resulted in no effect on LTP. (3) Coadministration of Zn2+ (15 microM) and N-methyl-D-aspartic acid (NMDA) (5 microM) significantly attenuated C fiber-evoked potentials, which was prevented by the NMDA receptor antagonist AP-5 (100 microM). The present results showed that Zn2+ may contribute to the modulation of the formation, but not the maintenance, of spinal LTP. NMDA receptors may be involved in Zn2+-induced modulation.
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PMID:The effects of Zn2+ on long-term potentiation of C fiber-evoked potentials in the rat spinal dorsal horn. 1178 44

The interaction between electroacupuncture and an N-methyl-D-aspartic acid (NMDA) receptor antagonist, (DL-2-amino-5-phosphonopentanoic acid; AP5), or an (+/-)-alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainite (AMPA/KA) receptor antagonist, (6,7-dinitroquinoxaline-2,3 (1H,4H); DNQX) administered intrathecally on carrageenan-induced thermal hyperalgesia and spinal c-Fos expression was investigated. The latency of paw withdrawal (PWL) from a thermal stimulus was used as a measure of hyperalgesia in awake rats. Intrathecal (i.t.) injection of 1 and 10 nmol AP5, but not DNQX, markedly increased the PWL of the carrageenan-injected paw. At a dose of 100 nmol, either AP5 or DNQX significantly increased the PWL of carrageenan-injected paw, with AP5 being more potent. The PWLs of the non-injected and normal saline (NS)-injected paws were not detectably affected by the administration of NMDA or AMPA/KA receptor antagonists at the doses tested. Unilateral electroacupuncture stimulation of the 'Zu-San-Li' (St 36) and 'Kun-Lun' (UB 60) acupuncture points (60 and 2 Hz alternately, 1-2-3 mA) contralateral to the carrageenan-injected paw significantly elevated the PWLs of carrageenan- and NS-injected paws. Although neither i.t. injection of 0.1 nmol AP5 nor 1 nmol DNQX alone had an effect on the PWL of the carrageenan- and NS-injected paws, both significantly potentiated electroacupuncture-induced analgesia in carrageenan-injected rats, especially 0.1 nmol AP5. Fos expression evoked by intraplantar (i.pl.) injection of carrageenan was examined in the spinal cord with immunohistochemical methods. Three hours after i.pl. injection of carrageenan, the number of Fos-like immunoreactive (Fos-LI) neurons was significantly increased in all the layers of the ipsilateral spinal cord at L(4-5), with the highest density in laminae I-II and V-VI. Intrathecally pre-administered AP5 (10 nmol) or DNQX (100 nmol) significantly reduced the total number of carrageenan-induced Fos-LI neurons. The reduction was most apparent in laminae I-II and IV-V. Similarly, following bilateral electroacupuncture stimulation of the 'Zu-San-Li' and 'Kun-Lun' acupuncture points, the numbers of carrageenan-induced Fos-LI neurons in laminae I-II and V-VI were also markedly reduced. When a combination of electroacupuncture with 10 nmol AP5 or 100 nmol DNQX was used, the level of Fos expression in the spinal cord induced by carrageenan was significantly lower than electroacupuncture or i.t. injection of AP5 or DNQX alone. These results demonstrate that electroacupuncture and NMDA or AMPA/KA receptor antagonists have a synergetic anti-nociceptive action against inflammatory pain. Furthermore, this study supports the idea that both NMDA and AMPA/KA receptors are involved in spinal nociceptive transmission in carrageenan-inflamed rats, with the former more preferentially mediating transmission of nociceptive information from cutaneous tissue.
Pain 2002 Oct
PMID:Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats. 1240 29

According to the classification criteria proposed by the American College of Rheumatology, fibromyalgia is a long-standing multifocal pain condition combined with generalised allodynia/hyperalgesia. It is the generalised allodynia/hyperalgesia that distinguishes fibromyalgia from other conditions with chronic musculoskeletal pain. Central sensitisation of nociceptive neurons in the dorsal horn due to activation of N-methyl-D-aspartic acid receptors and disinhibition of pain due to deficient function of the descending inhibitory system are probable pathogenic factors for allodynia/hyperalgesia. Furthermore, chronic pain is a chronic emotional and physical stressor. Chronic stress and chronic sleep disturbance are not specific for fibromyalgia but could be the causes of symptoms like fatigue, cognitive difficulties and other stress-related symptoms. They may also cause neuroendocrinological and immunological aberrations.
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PMID:Fibromyalgia--from syndrome to disease. Overview of pathogenetic mechanisms. 1281 64

N-methyl-D-aspartic acid (NMDA) is an agonist at the homonymous receptor implicated in the development of neuronal sensitization and its behavioral correlates. An effective modulation of the NMDA effects, achieved also by uncompetitive antagonists, could contribute to controlling pain symptoms in several neuropathic syndromes. Because nefopam is a known analgesic derivative of orphenadrine and of its congener diphenhydramine, both uncompetitive NMDA receptor antagonists, we tested the effect of nefopam on the developing pain and neuronal anomalies in an animal model of chronic pain with NMDA receptor involvement. A single intraperitoneal injection of nefopam was administered twenty minutes prior to the chronic constriction injury of the sciatic nerve (CCI rats). In the first 10 days, nefopam (30 mg/kg) significantly decreased behavioral signs of neuropathic pain and the stimulus-evoked electrophysiological anomalies in recordings at 14 days, with only slight manifestation afterwards. The dose of 20 mg/kg was ineffective. Nefopam injected after constriction was ineffective. In normal non-operated rats, Nefopam had no effect on the electrophysiological and behavioral parameters. Iontophoretic nefopam (1 mM, 50-80 nA, positive current) in normal rats did not change the spontaneous neuronal activity, but reduced the mean response to noxious stimuli and the concurrent iontophoretic NMDA evoked activity. In CCI rats, iontophoretic nefopam did not significantly modify the spontaneous hyperactivity but reduced significantly both the frequency of the responses to noxious stimuli, and the duration of the afterdischarge. We propose that nefopam exerts a preventive analgesic effect, with a possible role in modulating NMDA receptor-mediated effects in central sensitization.
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PMID:Neuronal sensitization and its behavioral correlates in a rat model of neuropathy are prevented by a cyclic analog of orphenadrine. 1290 43

Several studies have demonstrated that the nonselective opioid receptor antagonist naloxone produces a paradoxical antinociception in the formalin test. The opioid system is related to the serotonergic system for producing antinociception at the spinal level. Here we also asked whether systemic (i.p.) and intrathecal (i.t.) administrations of a nonselective serotonergic antagonist, methysergide, might produce paradoxical antinociception similar to naloxone in the mouse formalin test. A diluted formalin solution was injected into the mouse plantar region of the hind paw and the duration of licking responses was measured at periods of 0-5 min (1st phase) and 20-40 min (2nd phase) after formalin injection. Methysergide administered i.p. and i.t. showed an attenuated licking duration only in the 2nd phase. The effect observed in the 2nd phase was reversed in the 5,7-dihydroxytriptamine, but not N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine pretreated group of mice, suggesting that descending serotonergic, but not noradrenergic, systems are involved in the methysergide antinociception. To further investigate the mechanism by which methysergide inhibited the nociceptive behaviors induced by formalin, the antinociceptive effect of methysergide was also tested in substance P (i.t.) and excitatory amino acids (i.t.), such as glutamate, N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and kainic acid, which are major components in the formalin-induced nociceptive transmission in the spinal cord pain models. The duration of nociceptive behaviors shown in these models was significantly shortened by i.p. and i.t. administration of methysergide. These results suggest that methysergide also produces a paradoxical antinociception in various pain models including the formalin test, similar to the results of naloxone.
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PMID:Antinociceptive effects of methysergide in various pain models. 1292 83

To characterize the antinociceptive profiles of Angelica gigas NAKAI (ANG; Korean angelica), methanol extract from the dried roots of ANG was made and mice were administered orally at the various doses (from 0.25 to 3 g/kg). ANG produced the increased latencies of the tail-flick and hot-plate paw-licking responses in a dose-dependent manner. In acetic acid-induced writhing test, ANG dose-dependently decreased writhing numbers. Moreover, the cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced during both the 1st and the 2nd phases in a dose-dependent manner in ANG-treated mice. Furthermore, oral administration of ANG did not cause licking, scratching and biting responses induced by TNF-alpha (100 pg), IFN-gamma (100 pg) or IL-1beta (100 pg) injected intrathecally (i.t.), especially at higher dose (3 g/kg). Additionally, in ANG treated mice, the cumulative nociceptive response time for i.t. administration of substance P or capsaicin was dose-dependently diminished. Finally, nociceptive responses elicited by i.t. injection of glutamate (20 microg), N-methyl-D-aspartic acid (60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (13 ng) or kainic acid (12 ng) were decreased by oral administration of ANG. Our results suggest that ANG produces antinociception via acting on the central nervous system and shows antinociceptive profiles in various pain models, especially inflammatory pain.
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PMID:Antinociceptive profiles of crude extract from roots of Angelica gigas NAKAI in various pain models. 1295 72


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