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)

Cold water swim (CWS, 2 degrees C, 3.5 min) decreases the responsiveness to nociceptive stimuli in rats. The influence of various parameters of the CWS condition on stress-induced analgesia were evaluated by means of naltrexone effects. Naltrexone dose-dependently (but significantly only at high doses--21 mg/kg) partially antagonized 3.5 minute continuous CWS analgesia. Its effect was proportional to the duration of CWS. Naltrexone (14 mg/kg) significantly antagonized intermittent CWS-analgesia (18 10-sec exposures, 3/min) and enhanced the analgesia induced by 60 consecutive exposures (1 sec each, 12/min). These results demonstrate that naltrexone differentially affects CWS-analgesia, depending on specific parametric conditions of the stressor. In addition to activation of a non-specific naltrexone-insensitive analgesia-inducing system (not reduced by the drug in all the conditions studied) there appear to be three naltrexone sensitive systems: (1) a non-opioid analgesia-inducing system which mediates continuous CWS-analgesia; (2) an opioid analgesia-inducing system, involved in intermittent CWS-analgesia; and (3) a naltrexone-sensitive system which opposes the analgesic effect of 60 consecutive exposures. Thus, a highly specific relationship exists between certain parameters of the cold water stressor and the nature of the mechanisms which subserve the induced analgesia.
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PMID:Cold water stress analgesia in rats: differential effects of naltrexone. 609 Nov 60

The discriminative stimulus properties of nitrous oxide, an analgesic and anesthetic gas, were evaluated in rats trained to discriminate the effects of morphine or ethylketocyclazocine. Administration of nitrous oxide in concentrations as high as 80 percent did not produce generalization to the discriminative cue produced by morphine. Nitrous oxide did, however, generalize in a concentration-dependent manner in rats trained to discriminate ethylketocyclazocine, a psychotomimetic opioid. Naltrexone, a potent narcotic antagonist, did not block the generalization of nitrous oxide to ethylketocyclazocine. These results suggest that the subjective effects of nitrous oxide are similar to those produced by psychotomimetic drugs rather than those produced by morphine. These findings are in close agreement with those generated in man. Thus, nitrous oxide exhibits some pharmacological properties similar to those of morphine, for example, naloxone reversible analgesia. Yet, it has other properties such as subjective effects that are dissimilar from morphine.
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PMID:Nitrous oxide generalizes to a discriminative stimulus produced by ethylketocyclazocine but not morphine. 614 42

The effects of the ACTH 4-9 analog (Org 2766) and the COOH-terminal tripeptide of Org 2766 (Phe-D-Lys-Phe; PDLP) on retrieval of one-trial learning passive avoidance behavior were compared with those of beta-endorphin, [Met5]-enkephalin, [D-Ala2,Met5]-enkephalin, des-Tyr1-[Met5]-enkephalin and des-enkephalin-gamma-endorphin (DE gamma E). Amounts of intracerebroventricularly administered Org 2766, PDLP, [Met5]-enkephalin, [D-Ala2,Met5]-enkephalin and DE gamma E, which induced a comparable attenuation of passive avoidance behavior were determined. Pretreatment with the opiate antagonist naltrexone prevented the attenuating effect of these peptides on passive avoidance behavior except that of DE gamma E. The attenuating effect of Org 2766 and of [Met5]-enkephalin was reversed to facilitation of passive avoidance behavior in the presence of naltrexone. Subcutaneous treatment with Org 2766 and [D-Phe7]-ACTH 4-10 decreased electrical self-stimulation behavior elicited from the medial septal area. Naltrexone prevented the inhibitory effect of Org 2766 on this behavior, but not that of [D-Phe7]-ACTH 4-10. Although the attenuating effect of PDLP on passive avoidance behavior was not reduced by pretreatment with [Met5]-enkephalin- or beta-endorphin-antiserum, and PDLP induced neither analgesia nor excessive grooming, the data suggest that the inhibitory effect of Org 2766 and PDLP on passive avoidance behavior and electrical self-stimulation are mediated by endorphin systems in the brain.
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PMID:Naltrexone-sensitive behavioral actions of the ACTH 4-9 analog (Org 2766). 630 25

Naltrexone, a potent opiate antagonist, had both stimulatory and inhibitory effects on somatic growth in preweaning rats depending on dose. Daily injections of 50 mg/kg naltrexone, which blocked morphine-induced analgesia for 24 hr/day, resulted in increased body and organ weights, and acceleration in the appearance of physical characteristics and maturation of spontaneous motor activity. Naltrexone in a dosage of 1 mg/kg, which blocked morphine-induced analgesia for 4 hr/day, had the opposite effects. These results show that naltrexone can modulate growth, and suggest a role for the endorphins and opiate receptors in developmental events.
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PMID:Naltrexone modulates growth in infant rats. 631 64

Rats were implanted with an intrathecal catheter aimed at the lumbar enlargement (LE). Morphine hydrochloride (240 micrograms/day) was infused continuously on the spinal cord for 14 days with an osmotic minipump delivering 0.5 microliter/h solution or a bolus dose of naltrexone (37.5, 75 or 150 micrograms) was injected intrathecally. Intrathecally infused morphine delivered on the dorsum of the LE induced analgesia, as tested on the hot plate, whereas normal saline was without effect. Naltrexone caused hyperalgesia revealed as decreased threshold for vocalization to electrical stimulation of the tail. Rats with unilaterally sectioned sciatic nerves that were continuously infused with morphine on the dorsum of the LE autotomized significantly less than saline controls. Nerve sectioned rats injected with naltrexone had an overall level of autotomy similar to saline controls. However, autotomy had a somewhat earlier onset and was more severe with naltrexone than with saline. It is therefore concluded that intrathecal infusion of opiates specifically reduces autotomy, a behavior that may occur as a result of chronic discomfort or pain following nerve injury. Furthermore, the endogenous opiate system at the spinal level may be involved in the control of autotomy.
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PMID:The effects of intrathecal morphine and naltrexone on autotomy in sciatic nerve sectioned rats. 654 24

Naltrexone, an opiate antagonist, had both stimulatory and inhibitory effects, depending on the dosage, on the growth of S20Y neuroblastoma in A/Jax mice. Daily injections of 0.1 milligram of naltrexone per kilogram of body weight, which blocked morphine-induced analgesia for 4 to 6 hours per day, resulted in a 33 percent tumor incidence, a 98 percent delay in the time before tumor appearance, and a 36 percent increase in survival time. Neuroblastoma-inoculated mice receiving 10 milligrams of naltrexone per kilogram, which blocked morphine-induced analgesia for 24 hours per day, had a 100 percent tumor incidence, a 27 percent reduction in the time before tumor appearance, and a 19 percent decrease in survival time. Inoculation of neuroblastoma cells in control subjects resulted in 100 percent tumor incidence within 29 days. These results show that naltrexone can modulate tumor response and suggest a role for the endorphin-opiate receptor system in neuro-oncogenic events.
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PMID:Naltrexone modulates tumor response in mice with neuroblastoma. 686 37

Both the gamma-aminobutyric acid (GABA) mimetic, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the serotonergic agonist, MK 212 (6-chloro-2[ 1-piperazinyl ]pyrazine) are effective analgesic agents in the mouse hot plate assay. Naltrexone, however, fails to reverse the analgesia elicited by either compound. Acute injection of THIP potentiates the morphine analgesia and chronic administration of THIP produces a functional tolerance to its analgesic effects. MK 212 antagonizes the analgesia induced by either morphine or THIP. These results support the postulate that GABAergic and serotonergic synapses represent two synaptic mechanisms which participate in the modulation of pain threshold in a manner that is independent from opioid receptors. Moreover, GABA and serotonin appear to be able to modulate opioid-mediated analgesia in an opposing manner with GABAergic mechanisms facilitating and serotonergic mechanisms inhibiting morphine-induced antinociception.
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PMID:A comparison of the analgesic activities of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and 6-chloro-2[1-piperazinyl]pyrazine (MK 212). 687 80

Intrathecal injection of 0.25 micrograms of undecapeptide substance P antagonist (SPA) produced transient antinociception with a peak effect at 5 min. Increasing the SPA dose resulted in neurotoxicity. Intrathecal injection of the opioid peptide biphalin (BIP) produced antinociception for over 3 hrs without neurotoxicity. Co-administration of SPA (at subtoxic doses) increased BIP's antinociceptive effect. Naltrexone reversed analgesia due to BIP alone as well as after BIP+SPA.
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PMID:Spinal co-administration of peptide substance P antagonist increases antinociceptive effect of the opioid peptide biphalin. 751 Dec 1

The effect of chronic opioid antagonist treatment on the analgesic potency of six opioid agonists was compared to changes in opioid receptor density and the selectivity of each agonist for mu (DAMGO), delta (DPDPE) and kappa (U69,593) opioid receptors. Mice were implanted SC with a 15-mg naltrexone or placebo pellet for 8 days. The pellets were removed and 24 h later, mice were sacrificed and binding studies were conducted, or mice were tested in analgesia (tail-flick) dose-response studies. All six analgesics acted as full agonists for both placebo and naltrexone-treated mice. Naltrexone increased the analgesic potency of methadone, etorphine, fentanyl, meperidine, and oxycodone by 1.9-3.2-fold. The analgesic potency of propoxyphene was not increased significantly (1.3-fold). In saturation binding studies in brain homogenate, naltrexone increased the Bmax of mu, delta, and kappa opioid receptors by 86, 43, and 33%, respectively, without altering Kd. Competition binding studies for each receptor type were conducted in brains from untreated mice, and KIs were determined for each agonist. All agonists had greatest selectivity toward mu compared with delta and kappa receptors. There did not appear to be an obvious relationship between receptor selectivity and the magnitude of supersensitivity. These studies indicate that supersensitivity occurs for a broad range of opioid analgesics following chronic opioid antagonist treatment in the mouse. However, the selectivity of these agonists for mu, delta, and kappa receptors does not appear to correlate with differences in supersensitivity.
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PMID:Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: relationship to receptor selectivity. 766 82

The effects of naltrexone-precipitated withdrawal from buprenorphine on behavior and regional cerebral blood flow (rCBF) were studied in 11 opiate-dependent patients. Patients initially received buprenorphine, 2 mg sublingually, every day for 7 days. They were then challenged sequentially with placebo and naltrexone, 25 mg orally, before single photon emission computed tomography with technetium-99m-d,l-hexamethyl-propylene amine oxime as tracer. Behavioral ratings of withdrawal severity were made before and after naltrexone/placebo administration. Naltrexone produced significantly greater signs and symptoms of opiate withdrawal than placebo. Analysis of variance revealed no significant regionally specific effect of naltrexone on rCBF ratios. Severity of withdrawal, however, showed a significant negative correlation with rCBF in the anterior cingulate cortex following naltrexone. These results are interesting as the anterior cingulate region has been implicated in the emotional component of pain and in opiate-induced analgesia.
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PMID:SPECT regional cerebral blood flow alterations in naltrexone-precipitated withdrawal from buprenorphine. 770 Oct 33


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