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

Three animal models, based on genetic differences in endogenous opioid peptides and opioid receptors, are described. Obese mice and rats, whose pituitary opioid content is elevated, may be used to investigate eating disorders. Recombinant inbred strains of mice, which differ in brain opioid receptors and analgesic responsiveness, can be used for study of opioid- and nonopioid-mediated mechanisms of pain inhibition. Individual reactivity to opioids can be examined in C57BL/6 and DBA/2 inbred strains of mice. A model that combines a variety of opioid effects is offered and suggests the existence of a genetically determined dissociation of opioid effects on locomotor activity and pain inhibition. In addition, stimulatory locomotor responses in the C57BL/6 reaction type are linked to a high risk of drug addiction and facilitatory effects on adaptive processes, while high analgesic potency in the DBA/2 reaction type is accompanied by a low proneness to drug abuse and amnesic properties of opioids.
 ...
PMID:Opioids and behavior: genetic aspects. 283 10

In a first experiment, exposure of DBA/2 mice to a small number of attack bites by a C57BL/6 mouse resulted in low-intensity analgesia as assessed by the tail-flick test. The analgesia dissipated within 10 min and was insensitive to naloxone (10 mg/kg, sc) but was antagonized by the irreversible opioid antagonist beta-chlornaltrexamine (5 mg/kg, sc). In a second experiment, preexposure to a nonaggressive C57BL/6 opponent prevented low-intensity analgesia induced by a small number of attack bites 24 hr later. The preexposure effect was abolished by naloxone (10 mg/kg, sc) given before the nonaggressive confrontation. This suggests that the release of endogenous opioids during preexposure interferes with the subsequent activation of endogenous opioid-mediated pain control mechanisms.
 ...
PMID:Preexposure to a nonaggressive opponent prevents low-intensity, social-conflict analgesia in mice. 303 38

Fighting pairs of isolated DBA/2 mice showed a significant increase in tail-flick response latencies independent of whether opponents were losing or winning the combat. The effect lasted less than 10 min in both animals. Elevated pain thresholds were also found in isolates that attacked a nonaggressive conspecific, and were prevented by naltrexone (0.2 mg/kg), while a larger dose (1.0 mg/kg) inhibited the attack behavior. A small increase in pain threshold was observed after exposure of isolates to the test box alone, while isolation per se had no effect on baseline tail-flick latencies. The data demonstrate that endogenous pain suppressing systems are activated during attack and suggest that this opioid-mediated antinociception is a correlate of the isolation syndrome, reflecting enhanced arousal of the attacking animal.
 ...
PMID:Naltrexone-reversible pain suppression in the isolated attacking mouse. 320 18

Four experiments were designed to characterize long-term analgesic (LTA) reaction in attacked mice. In Experiment 1 we showed that analgesic reaction in DBA mice, induced by the stress of being attacked (30 or 50 bites), is reinstated upon reexposure to seven bites 24 hr later. The magnitude of the LTA response depended on the level of analgesia on Day 1 and was smaller than the original response. In Experiment 2 we showed that LTA was prevented by naloxone or beta-chlornaltrexamine given before exposure (50 bites) on Day 1. Results of Experiment 3 revealed that naloxone or beta-chlornaltrexamine injected before reexposure to seven bites on Day 2 antagonized LTA measured 10 min, but not 1 min, after reexposure. In Experiment 4 we showed that morphine substituted for being attacked on Day 1 failed to produce LTA. We concluded that pain inhibitory mechanisms remain in a state of increased readiness for at least 24 hr after attack stress and that activation of opioid systems is necessary but not sufficient to produce LTA, a response that is only partly sensitive to opioid antagonists.
 ...
PMID:Long-term analgesic reaction in attacked mice. 342 95

Exposure to repeated attack induces a long-lasting analgesia in male mice. Although this reaction has been linked to the special biological significance of defeat, earlier research has confounded defeat and exposure to further attack. In the present studies, DBA/2 intruder mice were individually placed into the home cages of aggressive conspecifics and removed immediately upon display of the species-characteristic upright submissive posture. Under these test conditions, intruders did indeed show a profound analgesia. However, in marked contrast to the antinociceptive effects of repeated attack, this reaction was of short duration (less than 10 min), was not blocked by naloxone (1-10 mg/kg, IP) and did not show cross-tolerance either to or from morphine (5 mg/kg, IP). These findings are discussed in relation to multiple endogenous pain inhibitory systems and their possible adaptive significance in murine social behaviour.
 ...
PMID:Acute non-opioid analgesia in defeated male mice. 371 72

Individually housed DBA/2 mice showed higher pain thresholds than grouped mice. Stress-induced analgesia was evident in grouped but not in isolated mice. Since also morphine injections did not result in analgesic effects in isolated mice, it is suggested that social isolation results in an increased release of opioids which may produce a decreased sensitivity at the opiate receptor level. The role of endogenous opioids in relation to social isolation is discussed.
 ...
PMID:Social isolation: effects on pain threshold and stress-induced analgesia. 668 78

The differential sensitivity following the administration of delta 9-THC to 3 mouse strains, C57BL/6, DBA/2 and ICR mice, indicated that some of the neurobehavioral changes may be attributable to genetic differences. The objective of this study was to determine the extent to which the cannabinoid (CB1) receptor is involved in the observed behavioral changes following delta 9-THC administration. This objective was addressed by experiments using: (1) DNA-PCR and reverse PCR; (2) systemic administration of delta 9-THC, and; (3) intracerebral microinjection of delta 9-THC. The site specificity of action of delta 9-THC in the brain was determined using stereotaxic surgical approaches. The intracerebral microinjection of delta 9-THC into the nucleus accumbens was found to induce catalepsy, while injection of delta 9-THC into the central nucleus of amygdala resulted in the production of an anxiogenic-like response. Although the DNA-PCR data indicated that the CB1 gene appeared to be identical and intronless in all 3 mouse strains, the reverse PCR data showed two additional distinct CB1 mRNAs in the C57BL/6 mouse which also differed in pain sensitivity and rectal temperature changes following the administration of delta 9-THC. It is suggested that the diverse neurobehavioral alterations induced by delta 9-THC may not be mediated solely by the CB1 receptors in the brain and that the CB1 genes may not be uniform in the mouse strains.
 ...
PMID:Neurobehavioral effects of delta 9-THC and cannabinoid (CB1) receptor gene expression in mice. 878 64

We found that the administration of ACTH4-10 fragment to newborn mice of several strains (DBA/2, CBA, C57BL/6J, CBARb, and BLRb) for 5 days from the second day of life led to changes of several behavioral characteristics of adult animals. The effect of peptide administration on exploratory behavior of mice and on following the direction of stimulus movement are opposite to those induced by pain stimulation, i.e., administration of a solvent. The results are interpreted as a possible antistress effect of the peptide, which is realized during the period of neurodifferentiation. These data are discussed in terms of a possible effect of the used peptide on differentiation of the nervous system.
 ...
PMID:[The action of ACTH 4-10 on the behavior of mice from different inbred strains]. 897 6

A growing literature documents the important influence of organismic factors such as sex and genotype on pain sensitivity and pain modulation. We recently determined that 3-min forced swims in 15 degrees C water produce non-opioid (i.e., naloxone-insensitive) analgesia in outbred Swiss-Webster mice of both sexes; this form of stress-induced analgesia (SIA) is significantly attenuated by the N-methyl-D-aspartate (NMDA) antagonist, dizocilpine (MK-801) in males, but not females. A pilot study designed to confirm the non-opioid and (in male mice) NMDAergic nature of 15 degrees C swim SIA in the C57BL/6J and DBA/2J inbred strains used widely in gene mapping was conducted, using the hot-plate (54 degrees C) assay of nociception. In female mice of both strains, 15 degrees C swim SIA was insensitive to antagonism by either naloxone (10 mg/kg, i.p.) or dizocilpine (0.1 mg/kg. i.p.). In male C57BL/ 6J mice, the observed SIA was naloxone-insensitive, but was attenuated by dizocilpine. This pattern of results is virtually identical to that obtained using Swiss-Webster mice in this and previous studies. However, male DBA/2J mice displayed SIA that was significantly attenuated by naloxone, but insensitive to dizocilpine antagonism. These findings support the hypothesis that genetic factors and sex, in addition to stressor parameters, can determine the selective recruitment of alternative central mechanisms of pain inhibition.
 ...
PMID:Sex and genotype determine the selective activation of neurochemically-distinct mechanisms of swim stress-induced analgesia. 898 10

The inbred mouse strains, DBA/2J (D2) and C57BL/6J (B6), display differential sensitivity to acute, thermal nociception as measured on the hot-plate (HP) assay. In an ongoing quantitative trait locus (QTL) mapping study designed to reveal genomic loci showing genetic linkage to HP sensitivity, a putative QTL on chromosome 4 (50-80 cM from the centromere) has been identified that appears to account for variability in this trait in male, but not female mice. An obvious candidate gene located in this same chromosomal region is Oprd1, which encodes the murine delta-opioid receptor. In an attempt to evaluate whether Oprd1 represents this sex-specific QTL for HP sensitivity, we tested D2 and B6 mice of both sexes for HP latencies (hindpaw-lift, -lick or -flutter) following systemic injections of saline, or the opioid receptor antagonists naloxone (NAL; 0.1 and 10 mg/kg), nor-binaltorphimine (nor-BNI; 5 mg/kg), naltrindole (NTI; 5 mg/kg), 7-benzylidenenaltrexone (BNTX; 0.7 mg/kg), or naltriben (NTB; 1 mg/kg). High-dose (10 mg/kg) NAL lowered HP latencies in D2, but not B6 mice, suggesting that the higher HP latencies exhibited by D2 mice reflect opioid mechanisms. HP latencies in both strains and both sexes were unaffected by pretreatment with low-dose (0.1 mg/kg) NAL or nor-BNI, suggesting that neither mu nor kappa receptors affect basal nociceptive sensitivity. The delta-receptor antagonist, NTI, and the delta2-specific antagonist, NTB, (but not the delta1-specific antagonist, BNTX) effectively lowered HP latencies in a strain- and sex-dependent manner: D2 male > B6 male > D2 female > B6 female. These data support the possibility that Oprd1 is a QTL mediating HP sensitivity in mice, and more generally illustrate the important roles of genetic background and gender in the perception of pain.
Pain 1997 Apr
PMID:Genetic sensitivity to hot-plate nociception in DBA/2J and C57BL/6J inbred mouse strains: possible sex-specific mediation by delta2-opioid receptors. 915 Mar 2


<< Previous 1 2 3 4 5 6 Next >>