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

In an attempt to determine the opioid receptor class(es) which underly the two opposing effects of naloxone in models of persistent pain, we tested the action of the selective delta antagonist naltrindole, and that of the kappa antagonist MR-2266 on the bidirectional effect of systemic naloxone in arthritic rats. As a nociceptive test, we used the measure of the vocalization thresholds to paw pressure. The antagonists were administered at a dose (1 mg/kg i.v. naltrindole, 0.2 mg/kg i.v. MR-2266), without action per se but which prevents the analgesic effect of the delta agonist DTLET (3 mg/kg, i.v.) or the kappa agonist U-69,593 (1.5 mg/kg, i.v.) respectively, and does not influence the effect of morphine (1 mg/kg i.v.) or the mu agonist DAMGO (2 mg/kg, i.v.) in these animals. In arthritic rats injected with the delta antagonist, the paradoxical antinociceptive effect produced by 3 micrograms/kg i.v. naloxone was not significantly modified (maximal vocalization thresholds (% of control) were 146 +/- 9% versus 161 +/- 7% in the control group). By contrast, the hyperalgesic effect produced by 1 mg/kg i.v. naloxone was significantly reduced (maximal vocalization thresholds were 87 +/- 4% versus 69 +/- 5% in the control group). In rats injected with the kappa antagonist, the antinociceptive effect of the low dose of naloxone was almost abolished (mean vocalization thresholds were 115 +/- 3% versus 169 +/- 7%) whereas the hyperalgesic effect of naloxone 1 mg/kg i.v. was not significantly modified (mean vocalization thresholds = 70 +/- 3% and 65 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effects of specific delta and kappa opioid receptor antagonists on the bidirectional dose-dependent effect of systemic naloxone in arthritic rats, an experimental model of persistent pain. 822 Nov 1

Supraspinal opioid analgesia is mediated in part by connections between the midbrain periaqueductal gray (PAG) and rostral ventral medulla (RVM) which includes the nuclei raphe magnus and reticularis gigantocellularis. Serotonergic 5HT2 and 5HT3 receptor subtypes appear to participate in this pathway since general and selective serotonergic antagonists microinjected into the RVM significantly reduced morphine analgesia elicited from the PAG. Since both an enkephalinergic pathway between the PAG and RVM and intrinsic enkephalinergic cells in the RVM exist, the present study evaluated the abilities of general (naltrexone), mu-selective (beta-funaltrexamine: B-FNA) and delta 2-selective (naltrindole) opioid receptor subtype antagonists microinjected into the RVM to alter morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. Mesencephalic morphine analgesia was significantly reduced after pretreatment in the RVM with naltrexone (1-10 micrograms), B-FNA (0.5-5 micrograms) or naltrindole (0.5-5 micrograms). Naltrexone in the RVM failed to alter basal nociceptive thresholds and none of the opioid antagonists were effective in reducing mesencephalic morphine analgesia when they were microinjected into placements lateral or dorsal to the RVM. These data indicate that mu and delta 2 opioid receptors in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG.
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PMID:Medullary mu and delta opioid receptors modulate mesencephalic morphine analgesia in rats. 825 87

The recognition and alleviation of animal pain is a growing veterinary and public concern. Pain can be of an acute or chronic nature with different behavioral manifestations. Physiologically, pain is a dynamic and complex phenomenon that produces changes in the central and autonomic nervous systems as well as in the endocrine system. Horses and other animals appear to possess an endogenous pain-suppressing system involving the brainstem and spinal cord. This system can modulate pain perception and the responses to it. The recently discovered endogenous opioid peptides (endorphins and enkephalins) appear to play a role in this system, which is activated by stress. Opioids (narcotic analgesics) act to selectively depress pain-sensitive cells. Opioid analgesics may act via multiple opioid receptors. Each subclass of opioid receptor has a different pharmacologic profile. Classical opioids that act at mu (morphine) receptors typically produce analgesia, increased locomotor activity, cardiorespiratory stimulation, and a decrease in intestinal peristalsis in the horse. Opioids that act at kappa receptors produce analgesia, sedation, ataxia, and minimal autonomic effects in the horse. Owing to their lack of excitatory actions, the kappa opioids represent a potentially useful class of analgesics for use in equine species. Local anesthetics depress all excitable cells and can diminish sensory, motor, and muscular function. They do not act selectively on pain fibers, although pain is among the first sensations lost following a nerve block. Local anesthetic activity is enhanced by increased extraneuronal pH, nerve cooling, increased nervous activity, coadministration of a vasoconstrictor or hyaluronidase, delayed systemic absorption, prolonged drug metabolism, and by using agents with high lipid solubility. Procaine, lidocaine, and mepivacaine are among the most widely used and studied agents in horses. These agents and/or their metabolites can be readily detected in urine; in some cases, for prolonged periods.
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PMID:Narcotics and local anesthetics. 829 18

The role of central N-methyl-D-aspartate (NMDA) receptors in the pathogenesis of central pain was examined in nine patients with central dysesthesia pain after spinal cord injury. The central pain syndrome included spontaneous continuous and intermittent pain as well as evoked pain. Pain was evoked by non-noxious stimulation of the skin (allodynia) and by repeated pricking of the skin (wind-up-like pain). The severity of continuous and evoked pain was examined before and after the intravenous infusion of either the NMDA receptor antagonist ketamine (6 micrograms/kg/min after a bolus dose of 60 micrograms/kg), the mu-opioid receptor agonist alfentanil (0.6 microgram/kg/min after after a bolus dose of 7 micrograms/kg), or placebo (0.9% NaCl). A randomized, double-blind, crossover study design was used. It was found that both continuous and evoked pain were markedly reduced by the blockade of NMDA receptors by ketamine as well as by the activation of mu-opioid receptors by alfentanil. Neither ketamine nor alfentanil significantly changed thresholds for the sensation of heat pain. The reduction of pain was not associated with severe side effects; the most severe side effect of ketamine was bothersome dizziness in one patient, and only modest side effects were caused by alfentanil. The present data provide clinical evidence that the development of central dysesthesia pain after traumatic spinal cord injury is dependent on the activation of central NMDA receptors. The results further indicate that mu-opioid receptors are involved in the control of this type of pain.
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PMID:Central dysesthesia pain after traumatic spinal cord injury is dependent on N-methyl-D-aspartate receptor activation. 858 48

Neuropeptide FF (NPFF) is a mammalian FMRFamide-like octapeptide with antiopioid properties that inhibits morphine-induced analgesia but also produces hyperalgesia. In the present study, a series of three experiments was carried out to investigate the interactions between opioid receptor stimulation and antiopioid systems. First, by using in vitro superfusion system with rat spinal cord slices, we showed that morphine stimulated NPFF release in a dose-dependent manner. The stimulating effect which was observed with morphine concentrations as low as 100 fM reached a maximum at 0.1 nM, then decreased and was ineffective at 10 microM. The morphine-induced release of NPFF was abolished by naloxone (1 microM) but unaltered by tetrodotoxin. Second, by an in vivo approach, we showed that a single heroin administration (2.5 mg/kg, s.c.) elicited in 30 min a drastic drop (38%) in spinal NPFF content. In a third experiment, we evaluated the capacity of naloxone in revealing an antiopioid component associated with opioid receptor stimulation. The administration of naloxone (1 mg/kg, s.c..) 25 min following that of heroin (2.5 mg/kg, s.c.) not only abolished the heroin-induced increase of tail-flick latency, but also lowered it under the basal value by 30%. These results indicate that opioid receptor stimulation activates both pain inhibitory and pain facilitatory systems in which NPFF may play a significant role and that opiate-induced analgesia is always partly masked.
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PMID:Simultaneous activation of spinal antiopioid system (neuropeptide FF) and pain facilitatory circuitry by stimulation of opioid receptors in rats. 862 8

Immune cell-derived opioid peptides can activate opioid receptors on peripheral sensory nerves to inhibit inflammatory pain. The intrinsic mechanisms triggering this neuroimmune interaction are unknown. This study investigates the involvement of endogenous corticotropin-releasing factor (CRF) and interleukin-1beta (IL-1). A specific stress paradigm, cold water swim (CWS), produces potent opioid receptor-specific antinociception in inflamed paws of rats. This effect is dose-dependently attenuated by intraplantar but not by intravenous alpha-helical CRF. IL-1 receptor antagonist is ineffective. Similarly, local injection of antiserum against CRF, but not to IL-1, dose-dependently reverses this effect. Intravenous anti-CRF is only inhibitory at 10(4)-fold higher concentrations and intravenous CRF does not produce analgesia. Pretreatment of inflamed paws with an 18-mer 3'-3'-end inverted CRF-antisense oligodeoxynucleotide abolishes CWS-induced antinociception. The same treatment significantly reduces the amount of CRF extracted from inflamed paws and the number of CRF-immunostained cells without affecting gross inflammatory signs. A mismatch oligodeoxynucleotide alters neither the CWS effect nor CRF immunoreactivity. These findings identify locally expressed CRF as the predominant agent to trigger opioid release within inflamed tissue. Endogenous IL-1, circulating CRF or antiinflammatory effects, are not involved. Thus, an intact immune system plays an essential role in pain control, which is important for the understanding of pain in immunosuppressed patients with cancer or AIDS.
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PMID:Expression of corticotropin-releasing factor in inflamed tissue is required for intrinsic peripheral opioid analgesia. 865 Feb 25

Outbred albino NMRI male mice encountering a brother in adulthood, after a long period of separation, show an opioid-dependent increase in pain threshold. Unrelated and unfamiliar males show no similar changes in pain sensitivity. This study investigates which kind of stimuli from the partner may be responsible for such a modification at the neural level. The tail-flick test is used as a measure of pain sensitivity. Exposure to the scent of the brother's home cage, as well as exposure to visual, olfactory and auditory stimuli and partial physical contact with the related male, are not sufficient to induce changes in nociception. Physical affiliative contact between males is higher in sib than in nonsib pairs, and a positive correlation exists in sib pairs between huddling behavior and pain sensitivity at the end of a 2-h social session. Siblings injected with naloxone, an opioid receptor blocker, show a decrease in social behaviors involving physical contact. These results suggest that physical affiliative contact between sibling mice may be responsible for the enhancement of nociceptive threshold.
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PMID:Reunion of separated sibling mice: neurobiological and behavioral aspects. 867 11

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 expression of the mRNAs for mu-, delta- and kappa-opioid receptors was studied in the lumbar spinal cord of the rats with the inflammation at their unilateral hindpaw using in situ hybridization technique. On 11 days after the first adjuvant inoculation, mu- and kappa-opioid receptor mRNA levels in laminae I-II of the spinal dorsal horn ipsilateral to the inflamed hindpaw were increased to 135.3 +/- 6.4% and 130.3 +/- 5.7%, respectively, compared with the contralateral side. At this time point, no significant differences in the mu- and kappa-opioid receptor mRNA expression were observed between ipsi- and contralateral sides of other laminae. On the other hand, no significant change was observed in the delta-opioid receptor mRNA expression throughout the laminae I-IX at any time points examined. These findings suggest the increase in the synthesis of mu- and kappa-, but not delta-, opioid receptors in the spinal laminae I-II during sustained inflammatory pain.
Pain 1996 Feb
PMID:Expression of mu- and kappa-, but not delta-, opioid receptor mRNAs is enhanced in the spinal dorsal horn of the arthritic rats. 874 Jun 15

Chronic pain remains a problem because it is often misdiagnosed and undertreated. Adverse effects and safety concerns associated with many analgesics have limited the use of these agents and contributed to the undertreatment of pain. With regard to the pharmacologic agents most commonly used to manage pain, centrally acting analgesics (e.g., morphine, codeine) are associated with respiratory depression, tolerance, and dependence, and most nonsteroidal anti-inflammatory drugs (NSAIDs) produce adverse gastrointestinal effects. New to the United States, tramadol HCl, which has been prescribed for almost 2 decades in Europe, is a single-entity, centrally acting analgesic that is effective for the management of moderate to moderately severe pain. Although the mechanism of action of this analgesic is not completely understood, animal models suggest that at least two complementary modes of action appear applicable: (1) binding of parent compound and mono-O-desmethyltramadol (M1 metabolite) to the mu-opioid receptor and (2) weak inhibition of norepinephrine and serotonin reuptake. Clinical experience suggests that tramadol appears to have a low potential for abuse or addiction. Results from clinical trials conducted in the United States as well as European postmarketing surveillance studies indicate that tramadol is an effective analgesic that may have a particularly important role in the management of chronic painful conditions.
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PMID:Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. 876 60


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