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)

We showed previously that (1 microgram) tetracaine block of PAG prevents the analgesic effect of PGC-ME injections, and also produces hyperalgesia regarding baseline tail-flick latencies. In the present study we injected PGC (unilaterally and bilaterally) with tetracaine so as to study its possible role in tonic descending inhibition of pain, as well as its necessity for analgesia due to PAG opiate injection. Two micrograms of tetracaine in PGC unilaterally or bilaterally failed to affect baseline tail-flick latencies and failed to attenuate at all the distinct analgesic effect of 2 micrograms ME injected into PAG. This analgesic effect was seen as a change in mean tail-flick latency from about 5.5 to 7.0 seconds 8-12 minutes post-injection, recovering to 5.5 second baseline by 25 minutes. Two micrograms tetracaine in nucleus raphe magnus (RM) was however sufficient to block the analgesic effect of RM stimulation. Thus PGC does not appear to participate in tonic descending pain inhibition (as PAG appears to do) nor is its functional integrity necessary for PAG ME analgesia (though PAG is necessary for PGC analgesia).
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PMID:Lack of effects of tetracaine in rat nucleus paragigantocellularis (PGC) on analgesia from periqueductal gray (PAG) met-enkephalin (ME) injections (in raphe magnus-blocking doses), and on baseline tail-flick latency. 792 2

Characteristics of the acupuncture point in producing acupuncture analgesia (AA) were examined by the inhibition of noxious responses in the brain stem reticular formation, potentials, and neuronal activity in the dorsal periaqueductal central gray (D-PAG), and analgesia caused by low frequency stimulation of the acupuncture point. As a result, stimulation of the muscle beneath the acupuncture point was found to be effective in producing AA. AA measured by tail flick, vocalization, and writhing tests was abolished by hypophysectomy, and by antiserum of beta-endorphin administered into the 3rd ventricle. The pathway from the D-PAG to the anterior hypothalamus (AA-AH) in the AA afferent pathway from the acupuncture point to the pituitary gland was determined. The lateral hypothalamus, lateral septum, cingulate bundle, dorsal-hippocampus, and habenulo-interpeduncular tract were found, in addition to regions previously found, to belong to the AA afferent pathway. A network of divergence and convergence in their rostral and caudal relations was observed. The AA afferent pathway diverges from the D-PAG, converges to the HP, and then projects to the AA-AH.
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PMID:The acupuncture point and its connecting central pathway for producing acupuncture analgesia. 842 Jun 35

Previous studies have shown that infusion of brain-derived neurotrophic factor (BDNF) into the midbrain, near the PAG and dorsal/median raphe nuclei, produced analgesia and increased activity in monoaminergic systems. Alterations in monoaminergic activity have also been implicated in the pathogenesis and treatment of depression. The present studies examined the ability of centrally administered BDNF to produce antidepressant-like activity in two animal models of depression, learned helplessness following exposure to inescapable shock and the forced swim test. In the learned helplessness paradigm, vehicle-infused rats pre-exposed to inescapable shock (veh/shock) showed severe impairments in escape behavior during subsequent conditioned avoidance trials, including a 47% decrease in the number of escapes and a 5 fold increase in escape latency, as compared to vehicle-infused rats which received no pre-shock treatment (veh/no shock). Midbrain BDNF infusion (12-24 micrograms/day) reversed these deficits, and in fact, BDNF-infused rats pre-exposed to inescapable shock (BDNF/shock) showed escape latencies similar to veh/no shock and BDNF/no shock rats. In the forced swim test, BDNF infusion decreased the immobility time by 70% as compared to vehicle-infused controls. Non-specific increases in activity could not account for these effects since general locomotor activity of BDNF- and vehicle-infused animals was not different. These findings demonstrate an antidepressant-like property of BDNF in two animal models of depression, which may be mediated by increased activity in monoaminergic systems.
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PMID:Antidepressant-like effect of brain-derived neurotrophic factor (BDNF). 898 20

Exposure of embryonic CNS neurons to BDNF in vitro causes down-regulation of TrkB protein and mRNA, and an attenuation of functional responses to acute neurotrophin stimulation. In order to investigate ligand-mediated regulation of TrkB in vivo, we infused BDNF into the midbrain, near the periaquaductal grey-dorsal raphe (PAG-DR), or into the olfactory bulb of adult rats. Midbrain infusion of BDNF produced analgesia that was sustained for the duration of BDNF delivery. Analysis of TrkB receptor levels revealed that at the point when the maximal analgesic effect of BDNF was obtained, there was a concommitant 75% decrease in full-length TrkB protein at the infusion site. After discontinuation of infusion, levels of TrkB recovered toward base line. Interestingly, TrkB protein levels were not accompanied by decreased trkB mRNA levels. To determine if BDNF infusion decreased TrkB protein levels in other brain areas and whether trkB mRNA might be down-regulated in the cell bodies of neurons projecting to the infusion site, we infused BDNF into the olfactory bulb. Following a 12-day infusion of BDNF, TrkB protein levels decreased within the bulb to a similar extent as in the PAG-DR. This decrease in receptor protein, however, was not accompanied by decreased trkB mRNA levels in the olfactory cortex, which is afferent to the bulb. Taken together, our data suggest that decreases in TrkB receptor protein at the site of BDNF infusions in the adult brain represent receptor turnover, but this is not associated with altered expression of trkB mRNA or attenuation of the pharmacological effects of BDNF.
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PMID:Effects of BDNF infusion on the regulation of TrkB protein and message in adult rat brain. 918 9

This study found that bilateral electrolytic lesions of the ventrolateral orbital cortex (VLO) markedly reduced the inhibitory effects of high intensity electroacupuncture (EA) at "Zusanli" point on tail flick reflex in lightly anesthetized rats, but did not influence the inhibitory effects of low intensity EA stimulation. The results show that the VLO is involved in acupuncture analgesia produced by activation of small afferent fibers with high intensity electroacupunture. Results of this study provide further support for a hypothesis that spinal cord-Sm-VLO-PAG-spinal cord may constitute a negative feedback loop of nociceptive modulation. The analgesic effects produced by high intensity electroacupuncture may be mediated by this loop leading to depression of the nociceptive inputs at the spinal cord level.
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PMID:[Effects of bilateral lesions of ventrolateral orbital cortex on the rat tail flick reflex inhibition evoked by electroacupuncture]. 938 72

The experiments were performed on the anesthetized rats. Single unit was recorded extracellularlly from the thalamic nucleus submedius (Sm) with glass micropipettes. The responses of Sm neurons were examined to electrical stimulation of the peroneal nerve and "Zusanli" point. The results show that most (81%) of the neurons in Sm responded to electrical stimulation of the peroneal nerve with afferent C fiber excitation, and this response increased following increase of the stimulation intensity and pulse numbers. It was found that electrical stimulation of the "Zusanli" point could activate the Sm neuronal activities with higher intensity threshold compared to that of the peroneal nerve stimulation, and the response properties of Sm neurons to acupoint stimuli were similar to those to stimulation of peroneal nerve. These results provide support for the hypothesis that a negative feedback loop consisting of spinal cord-Sm-VLO-PAG-spinal cord responsible for nociceptive modulation is involved in acupuncture analgesia, especially in analgesia produced by electroacupuncture-evoked activation of the afferent C fibers.
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PMID:[Responses of neurons in thalamic nucleus submedius to electrical stimulation of peroneal nerve and "zusanli" point in rats]. 938 15

1. [Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 (Phepsi), a tridecapeptide analogue of orphanin FQ/nociceptin (OFQ/N), was introduced as a competitive antagonist of opioid receptor-like orphan receptor (ORL1) in guinea-pig ileum and mouse vas deferens preparations in vitro but was recently found to act as an agonist in vivo. 2. In the periaqueductal gray, a site enriched with both OFQ/N and ORL1 and involved in OFQ/N-induced hyperalgesia and anti-analgesia, the effects of Phepsi and OFQ/N on the membrane current were studied using whole cell patch clamp recording technique in rat brain slices. 3. OFQ/N (0.01 - 1 microM) activated an inwardly rectifying type of K+ channels in ventrolateral neurons of PAG. Phepsi (0.03 - 1 microM), like OFQ/N, also activated this inward rectifier but had only 30% efficacy of OFQ/N. 4 At maximal effective concentration (1 microM), Phepsi reversed the increment of K+ conductance induced by OFQ/N (300 nM) by 46%. On the other hand, Phepsi also prevented the effect of OFQ/N if pretreated before OFQ/N. 5 It is suggested that Phepsi acts as a partial agonist of ORL1 that mediates the activation of inwardly rectifying K+ channels in ventrolateral neurons of rat periaqueductal gray.
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PMID:[Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 activation of an inward rectifier as a partial agonist of ORL1 receptors in rat periaqueductal gray. 1049 40

The transneuronal tracer, pseudorabies virus (PRV), was used to identify pathways from the uterine cervix which may be involved in induction of analgesia and abbreviation of estrus by vaginocervical stimulation. In Experiment I, PRV immunoreactivity (PRV-IR) in brain and spinal cord was examined 3-5 days after injection into the cervix of ovariectomized (OVX) female rats given estrogen (E) or control treatments. No differences in viral labeling were observed between OVX and OVX+E females at any time. PRV-infected cells were observed to increase as a function of time and at progressively higher CNS levels. PRV-IR neurons were first observed on day 3 post-infection at L6 in the SPN. Increased labeling was observed at day 4 in the SPN and the DGC at L6 and S1 spinal segments. Dorsal horn neurons showed PRV-IR by 4.5 days. Five days post-infection, labeling was seen in the IML and lamina X in T12-L1 segments, and in medullary raphe, A5, nPGi, nGi, DMV, lateral reticular, Barrington's nuclei, and in the midbrain PAG. In Experiment II, the effects of bilateral L6 dorsal root rhizotomy (RH) combined with unilateral (UPx) or bilateral (BPx) pelvic nerve transection on PRV infectivity were examined 5 days after infection. Despite reductions in substance P labeling in the dorsal horn following RH, PRV-IR neurons persisted in this area. In RH+UPx females, labeling persisted bilaterally in the SPN and DGC at L6. RH+BPx almost completely eliminated the PRV labeling in L6 and S1. Horizontal sections showed distinct patterns of infectivity within the IML of thoracolumbar and SPN of lumbosacral segments consistent with infection in the hypogastric and pelvic nerves, respectively. Our data indicate that retrograde transport of PRV occurs via the hypogastric and pelvic nerves after injection of the virus into the uterine cervix. Furthermore, significant intraspinal processing is likely to occur between thoracolumbar and lumbosacral levels in the modulation of reproductive tract function.
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PMID:Pseudorabies virus tracing of neural pathways between the uterine cervix and CNS: effects of survival time, estrogen treatment, rhizotomy, and pelvic nerve transection. 1071 75

To summarize, although there are multiple potential target nuclei for modulating pain transmission and several candidate efferent pathways that exert modulatory control, the most completely described pain modulating circuit includes the amygdala, PAG, DLPT and RVM in the brainstem. Through descending projections, this circuit controls both spinal and trigeminal dorsal horn pain transmission neurons and mediates both opioid and stimulation produced analgesia. Several different neurotransmitters are involved in the modulatory actions of this circuit, which exerts bi-directional control of pain through On cells that facilitate and Off cells that inhibit dorsal horn nociceptive neurons. There is evidence that this circuit contributes to analgesia in humans and may be activated by acute stress or the expectation of relief. Conversely, through the facilitating effect of On cells, this circuit is theoretically capable of generating or enhancing perceived pain intensity. Such an effect could provide a physiological mechanism for the pain enhancing actions of mood, attention and expectation.
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PMID:Pain modulation: expectation, opioid analgesia and virtual pain. 1073 63

Objective To investigate the analgesia induced by cobrotoxin (CT) from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally (33.3, 50, 75 mu g/kg), intra-cerebral venticularly (2.4 mu g/kg) or microinjected into periaqueductal gray (PAG, 1.2 mu g/kg). The antinoCiceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im or 10 mg/kg, ip) or naloxone (3 mg/kg, ip). The effect of CT on motor activity was tested using the Animex test. Results CT (33.3, 50 and 75 mu g/kg, ip) exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 mu g/kg (1/23th of a systemic dose) produced marked analgesic effects. Microinjection of CT 1.2 mu g/kg (1/46th of systemic dose) into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg (im) or naloxone at 3 mg/kg (ip) failed to block the analgesic effects of CT, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception (75 mu g/kg), CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT's analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.
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PMID:A short-chain alpha-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia. 1768 6


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