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)

There is substantial evidence that magnetic fields can reduce opiate-induced analgesia, with alterations in calcium channel function and/or calcium ion flux being implicated in the mediation of these inhibitory effects. The present experiments were designed to examine the effects of protein kinase C (PKC), a calcium/diacylglycerol/phospholipid-dependent protein kinase, on opiate-induced analgesia and its involvement in mediating the inhibitory effects of exposure to magnetic fields. We observed that morphine-induced antinociception, or 'analgesia', in the land snail, Cepaea nemoralis, as measured by the enhanced latency of response to a thermal (38.5 degrees C) stimulus, was reduced in dose-related manner by the PKC activator, SC-9. Exposure of snails for 2 h to a low intensity (1.0 gauss rms) 60-Hz magnetic field also reduced morphine-induced analgesia. The inhibitory effects of the 60-Hz magnetic field on morphine-induced analgesia were significantly reduced by the PKC inhibitors, H-7 and H-9, and significantly enhanced by the PKC activator, SC-9. The non-specific protein kinase inhibitor, HA-1004, and the preferential calmodulin inhibitor, W-7, had no significant effects on either morphine-induced analgesia or the inhibitory actions of exposure to the magnetic fields. These results suggest that: (1) PKC has antagonistic effects on opiate-mediated analgesia in the snail, Cepaea, and (2) that the inhibitory effects of magnetic fields on opiate-induced analgesia involve alterations in PKC.
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PMID:Evidence for the involvement of protein kinase C in the modulation of morphine-induced 'analgesia' and the inhibitory effects of exposure to 60-Hz magnetic fields in the snail, Cepaea nemoralis. 193 19

Calcium is an important intracellular messenger that interacts with Ca(2+)-binding proteins, such as calmodulin (CaM), to activate several intracellular enzymes. The involvement of Ca2+ in the transmission of nociceptive signals has been demonstrated at the spina level. Specifically, spinal sensitization induced by persistent nociceptive stimulation seems to be related to an increase of cytosolic calcium and the subsequent activation of several enzymes, some of which are Ca2+/CaM dependent. In order to elucidate the possible implication of calmodulin in these pain processes, we have studied the effect of two calmodulin inhibitors (W-7 and calmidazolium) or the formalin and tail-flick tests in rats after their intrathecal administration. Antinociceptive effects were observed in both tests by injecting 0.12-1 mumol/rat of calmidazolium and 0.25-2 mumol/rat of W-7. Calmidazolium was more potent than W-7 in inhibiting both phases of the formalin test, whereas lower doses of W-7 in comparison to calmidazolium affected the tail-flick latencies. In addition, both drugs induced, at high doses, a muscular flaccidity of the hindlimbs that impaired normal walking in the rats. This effect caused; significant reduction of the rotarod performance when 1 mumol/rat of calmidazolium or 2 mumol/rat of W-7 were injected. Overall, our results show that calmodulin inhibitors are capable of producing spinal analgesia on phasic and tonic noxious stimuli in rats, thus rendering them a promising potential as analgesics.
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PMID:Calmodulin inhibitors induce spinal analgesia in rats. 888 61

The attenuation of opioid peptide-mediated antinociception is a well-established effect of extremely low frequency (ELF) electromagnetic fields with alterations in calcium channel function and/or calcium ion flux and protein kinase C activity being implicated in the mediation of these effects. The present study was designed to examine the effects of nitric oxide (NO) and calcium ion/calmodulin-dependent nitric oxide synthase (NOS) on opioid-induced antinociception and their involvement in mediating the inhibitory effects of exposure to ELF magnetic fields. We observed that enkephalinase (SCH 34826)-induced, and likely enkephalin-mediated, antinociception in the land snail, Cepaea nemoralis, as measured by the enhanced latency of a foot withdrawal response to a thermal (40 degreesC) stimulus, was reduced by the NO releasing agent, S-nitro-N-acetylpenicillamide (SNP), and enhanced by the NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME). Exposure of snails to an ELF magnetic field (15 min, 60 Hz, 141 microT peak) also reduced the enkephalinase-induced antinociception. The inhibitory effects of the 60-Hz magnetic field were significantly reduced by the NO synthase inhibitor, l-NAME, and significantly enhanced by the NO releasing agent, SNP, at dosages which by themselves had no evident effects on nociceptive sensitivity. These results suggest that: (1) NO and NO synthase have antagonistic effects on opioid-induced analgesia in the snail, Cepaea and (2) the inhibitory effects of ELF magnetic fields on opioid analgesia involve alteration in NO and NO synthase activity.
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PMID:Evidence for the involvement of nitric oxide and nitric oxide synthase in the modulation of opioid-induced antinociception and the inhibitory effects of exposure to 60-Hz magnetic fields in the land snail. 979 29

Tolerance and dependence induced by chronic delta-9-tetrahydrocannabinol (THC) administration were investigated in mice. The effects on body weight, analgesia and hypothermia were measured during 6 days of treatment (10 or 20 mg kg(-1) THC twice daily). A rapid tolerance to the acute effects was observed from the second THC administration. The selective CB-1 receptor antagonist SR 141716A (10 mg kg(-1)) was administered at the end of the treatment, and somatic and vegetative manifestations of abstinence were evaluated. SR 141716A administration precipitated several somatic signs that included wet dog shakes, frontpaw tremor, ataxia, hunched posture, tremor, ptosis, piloerection, decreased locomotor activity and mastication, which can be interpreted as being part of a withdrawal syndrome. Brains were removed immediately after the behavioural measures and assayed for adenylyl cyclase activity. An increase in basal, forskolin and calcium/calmodulin stimulated adenylyl cyclase activities was specifically observed in the cerebellum of these mice. The motivational effects of THC administration and withdrawal were evaluated by using the place conditioning paradigm. No conditioned change in preference to withdrawal associated environment was observed. In contrast, a conditioned place aversion was produced by the repeated pairing of THC (20 mg kg(-1)), without observing place preference at any of the doses used. This study constitutes a clear behavioural and biochemical model of physical THC withdrawal with no motivational aversive consequences. This model permits an easy quantification of THC abstinence in mice and can be useful for the elucidation of the molecular mechanisms involved in cannabinoid dependence.
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PMID:Behavioural and biochemical evidence for signs of abstinence in mice chronically treated with delta-9-tetrahydrocannabinol. 988 86

Drugs able to inhibit calmodulin activation can prevent some consequences of the rise in intracellular calcium. It has recently been shown that intrathecal injection of calmodulin inhibitors induce analgesia in rats. We study here the effect induced by the calmodulin inhibitor, calmidazolium, on the activity of dorsal horn neurons driven by noxious and non-noxious stimuli. Extracellular recordings of convergent (n = 12), low-threshold mechanoreceptive (n = 5) and proprioceptive (n = 5) units were made in the presence of calmidazolium. Calmidazolium (600 micrograms) reduced the noxious (50 degrees C) heat-evoked responses obtained in convergent neurons. On the contrary, the non-noxious tactile responses obtained in low-threshold mechanoreceptive neurons as well as the joint movement-evoked responses obtained in proprioceptive units remained unmodified. We conclude that calmidazolium can block nociceptive processing in the spinal cord and that this fact can help to explain the analgesic effects that intrathecal W-7 and calmidazolium induce in behavioral tests.
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PMID:Spinal effects of the calmodulin inhibitor calmidazolium on dorsal horn neurons in the rat. 1023 74

The intrathecal (IT) administration of NMDA in rodents has usually been reported to produce hyperalgesic reactions, although some articles describe that spinal NMDA can lead to analgesia. We show here that the nociceptive behavior (biting, scratching, licking; BSL) observed after NMDA injection (1-8 microg/rat; IT) is followed by a long period of increased tail-flick latencies, not longer detected 24 h after NMDA administration. The NMDA-receptor antagonist CPP (10-100 ng/rat; IT) blocked the BSL behavior induced by NMDA. In the tail-flick test, this antagonist induced analgesia by itself, and was able, at 30 ng/rat, to prevent the NMDA-mediated analgesia. The implication of opiate mechanisms was discarded since naloxone (3 and 10 mg/kg; IP) did not antagonize NMDA-induced analgesia. Finally, the involvement of the intracellular calcium binding protein calmodulin was assessed. The calmodulin inhibitor, calmidazolium (30-300 microg/rat; IT) only blocked the excitatory effect (BSL) without modifying the tail-flick analgesia produced by NMDA (4 microg). These results show that a single intrathecal administration of NMDA sequentially induces both nociceptive and antinociceptive, nonopiate responses in rats.
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PMID:Intrathecal N-methyl-D-aspartate (NMDA) induces paradoxical analgesia in the tail-flick test in rats. 1076 14

The influence of the calcium channel blockers (CCBs) nifedipine, verapamil and diltiazem, and the calmodulin antagonist trifluoperazine on the antinociceptive activity of acetaminophen was studied in male albino mice. The nociceptive response was determined by the acetic acid writhing test. Nifedipine (50 or 20 mg/kg), verapamil (20 mg/kg), diltiazem (70 mg/kg) and trifluoperazine (3 mg/kg) were administered orally alone or 1 h before acetaminophen (100 mg/kg). Nifedipine (50 mg/kg), verapamil, diltiazem and trifluoperazine administered alone demonstrated significant antinociceptive effects compared to controls. Nifedipine, verapamil, diltiazem and trifluoperazine applied 1 h before acetaminophen potentiated its antinociceptive activity, which was strongest in mice injected with verapamil and nifedipine (20 mg/kg). It was established that 1 h after nifedipine (50 mg/kg) treatment, cytochrome P450 content, NADPH cytochrome c reductase and ethylmorphine-N-demethylase (EMND) activities were increased in the liver microsomes. Verapamil, diltiazem and trifluoperazine did not change the drug metabolizing enzymes studied. It is assumed that their effect on acetaminophen analgesia is not associated with the changes in acetaminophen oxidative metabolism in the liver.
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PMID:Effects of nifedipine, verapamil, diltiazem and trifluoperazine on the antinociceptive activity of acetaminophen. 1134 95

We examined which of the known properties of trifluoperazine, including calmodulin inhibition, are involved in its analgesic effect. Furthermore, we tried to find any possible interaction between opioidergic system and calmodulin inhibition-induced analgesia. Intrathecal trifluoperazine (1, 10, 100 microg) showed a biphasic effect in the formalin test; i.e., analgesia at relatively low doses (1, 10 microg) and hyperalgesia at a high dose (100 microg). No analgesic effects were observed after intrathecal injection of sulpiride (1, 10, 100 microg), atropine (0.1, 1, 10 microg), phentolamine (0.1, 1, 10 microg) and brompheniramine (0.1, 1, 10 microg). Meanwhile, intrathecal calmidazolium (10, 50, 250 microg) induced a dose-dependent analgesia. Histamine (1 microg), physostigmine (1 microg), bromocriptine (1 microg) and norepinephrine (1 microg) did not affect trifluoperazine-induced analgesia. Calcium (20 microg) attenuated the antinociceptive effect of trifluoperazine and inhibited the analgesic effect of calmidazolium. Finally, naloxone (2 mg/kg) decreased trifluoperazine-induced antinociception but did not have any effects on calmidazolium-induced analgesia. We concluded that calmodulin inhibition may be involved in the analgesia produced by trifluoperazine. With increasing doses of trifluoperazine, the algesic effect seems to overcome the analgesic effect. It is also suggested that the opioidergic system does not interact with calmodulin inhibition-induced analgesia even though this system has a possible role in trifluoperazine-induced analgesia.
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PMID:Involvement of calmodulin inhibition in analgesia induced with low doses of intrathecal trifluoperazine. 1192 15

We investigated how dizocilpine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, affects the development of morphine dependence in mice. Co-administration of dizocilpine (0.25 mg/kg) and morphine (10 mg/kg) for 5 days attenuated the development of tolerance to the antinociceptive effects of morphine. The withdrawal manifestation induced by the naloxone-challenge (5 mg/kg) was significantly reduced in mice that were treated with a combination of dizocilpine and morphine, compared to the mice treated with morphine and saline. The present study revealed a significant increase in c-Fos protein expression in the cortex and thalamus of mice showing naloxone-precipitated withdrawal syndrome. The combination of dizocilpine and morphine prevented the increase of c-Fos protein expression in the cortex and thalamus. Interestingly, repeated co-administration of dizocilpine and morphine prevented the withdrawal-induced phosphorylation of Ca2+/calmodulin kinase II (p-CaMK II) in the cortex, but not in the thalamus. Acute dizocilpine treatment prior to the naloxone-challenge and repeated treatment with dizocilpine alone had no effect on analgesia, withdrawal manifestations, p-CaMK II levels or c-Fos protein levels. These results showed that co-administration of dizocilpine and morphine prevented the development of morphine tolerance and dependence and suggested that the preventive effect of dizocilpine results from the regulation of c-Fos protein expression, which is possibly involved in the activation of the Ca2+/calmodulin-dependent signal cascade in the cortex.
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PMID:Molecular mechanisms in dizocilpine-induced attenuation of development of morphine dependence: an association with cortical Ca2+/calmodulin-dependent signal cascade. 1519 94

The calmodulin (CaM) inhibitor trifluoperazine (TFP) can produce analgesia when given intrathecally to rats; however, the mechanism is not known. We asked whether TFP could modulate the Na(v)1.7 sodium channel, which is highly expressed in the peripheral nervous system and plays an important role in nociception. We show that 500 nM and 2 muM TFP induce major decreases in Na(v)1.7 and Na(v)1.4 current amplitudes and that 2 muM TFP causes hyperpolarizing shifts in the steady-state inactivation of Na(v)1.7 and Na(v)1.4. CaM can bind to the C-termini of voltage-gated sodium channels and modulate their functional properties; therefore we investigated if TFP modulation of sodium channels was due to CaM inhibition. However, the TFP inhibition was not replicated by whole cell dialysis of a calmodulin inhibitory peptide, indicating that major effects of TFP do not involve a disruption of CaM-channel interactions. Rather, our data show that TFP inhibition is state dependent and that the majority of the TFP inhibition depends on specific amino-acid residues in the local anesthetic receptor site in sodium channels. TFP was also effective in vivo in causing motor and sensory blockade after subfascial injection to the rat sciatic nerve. The state-dependent block of Na(v)1.7 channels with nanomolar concentrations of TFP raises the possibility that TFP, or TFP analogues, might be useful for regional anesthesia and pain management and could be more potent than traditional local anesthetics.
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PMID:Inhibition of Nav1.7 and Nav1.4 sodium channels by trifluoperazine involves the local anesthetic receptor. 1680 47


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