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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that non-opioid defensive analgesia in male mice is potently inhibited by the 5-HT3 receptor antagonist, ondansetron. The present series of experiments was conducted to further explore the involvement of 5-HT3 receptor mechanisms in this particular form of adaptive inhibition of pain. The drug ICS 205-930 significantly attenuated the reaction at 1.25-2.5 micrograms/kg, with smaller and larger doses being ineffective. Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively. Although MDL 72699, the quaternary salt of MDL 72222, also inhibited the reaction, this effect was seen at comparatively large doses (0.5-1.0 mg/kg) only. None of the compounds tested had significant intrinsic effects of tail-flick latencies, over the dose ranges tested. These findings indicate that 5-HT3 receptor mechanisms may have an important modulatory role in certain forms of "stress" analgesia. Data are discussed in relation to the consistent profile of partial inhibition produced by 5-HT3 receptor antagonists in this model.
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PMID:Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699. 140 95

This study was designed to determine if morphine administered intrathecally (IT) interacts with serotonergic or noradrenergic nerve terminals in the spinal cord to produce analgesia on the spinally mediated tail-flick test. Male Sprague-Dawley rats were fitted with IT catheters. One week later, animals were spinally pretreated with receptor antagonists selective for opioid, serotonin or alpha-adrenoceptors, and the ability of these agents to alter spinal morphine-induced antinociception was assessed. Morphine dose-dependently elevated tail-flick latency in a naltrexone-reversible manner. The serotonin receptor antagonists spiroxatrine (5-HT1A), pindolol (5-HT1B), ritanserin (5-HT2) and ICS 205-930 (5-HT3) attenuated the spinal analgesic effects of morphine. In contrast, the alpha 1 and alpha 2-adrenoceptor antagonists prazosin and yohimbine, respectively, did not alter morphine-induced elevations in tail-flick latency. These data substantiate earlier reports that spinal morphine-induced antinociception relies on an opioid receptor-mediated component in addition to a local serotonergic component. The finding that the alpha-adrenoceptor antagonists did not alter the antinociceptive effects of IT morphine suggests that spinal norepinephrine does not contribute to the analgesic effects of the opiate.
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PMID:Serotonin contributes to the spinal antinociceptive effects of morphine. 168

1. Serotonin (5-HT) and selective 5-HT receptor agonists were administered intrathecally (i.t.) in rats, and the antinociceptive efficacy of these agents was assessed on the tail-flick and hot plate tests. 2. The 5-HT receptor agonists examined in this study included the 5-HT1A agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), the 5-HT1B agonist m-trifluoromethylphenylpiperazine (TFMPP), the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT3 agonist phenylbiguanide (PBG). 3. None of these agents produced significant elevations in tail-flick latency (TFL) at doses which produced elevations in hot plate latency (HPL). 4. In contrast, the i.t. dose of 5-HT which elevated TFL also produced analgesia on the hot plate test. 5. Serotonin-induced elevations in TFL were reversed by pindolol, ritanserin and ICS 205-930, suggesting that 5-HT interacts with more than one 5-HT site in the spinal cord to produce analgesia on the tail-flick test. 6. The finding that ritanserin reversed 5-HT-induced elevations in HPL suggests that the 5-HT2 site is primarily responsible for mediating the spinal antinociceptive effects of 5-HT on the hot plate test.
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PMID:Analgesic effects of serotonin and receptor-selective serotonin agonists in the rat spinal cord. 182 46

Although 5-HT is clearly involved in spinal analgesia, its mode of action remains obscure, perhaps because it has multiple and often opposing effects mediated by its multiple receptor subtypes. This investigation uses selective agonists and antagonists directed at the most recently defined class of 5-HT receptors (5-HT3 receptors) in behavioral and electrophysiological studies of nociception in the spinal cord of rodents. The results demonstrate uniformly inhibitory effects of a selective 5-HT3 agonist on responses to noxious stimuli. Intrathecally administered 2-methyl 5-HT produced dose-dependent antinociception in the tail-flick test and inhibited behaviors elicited by intrathecally administered agonists for excitatory amino acid and neurokinin receptors, namely NMDA and substance P (SP). All 20 dorsal horn neurons we examined, which projected to the brain and responded to both noxious stimuli and NMDA, were inhibited in a current-related manner by this 5-HT3 agonist applied iontophoretically. Both the behavioral and electrophysiological effects were blocked not only by the 5-HT3 antagonists zacopride and ICS 205-930, but also by antagonists to the inhibitory amino acid GABA. Therefore, 5-HT via an action at 5-HT3 receptors may evoked release of GABA, which may in turn inhibit nociceptive transmission at a site postsynaptic to terminals of primary afferent fibers. If the descending serotonergic analgesic system in humans operates similarly, understanding it may enable the development of new nonopioid, nonaddictive analgesics.
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PMID:Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA. 206 67

In a previous study, prolonged low-frequency muscle stimulation in the hind leg of the fully conscious spontaneously hypertensive rat (SHR) was shown to induce a long-lasting reduction of blood pressure. It was also shown that opioid and serotonergic (5-HT) systems were involved. More recently, we have shown that the 5-HT1 receptors are involved in the post-stimulatory decrease in blood pressure. In the present study, the influence of this type of muscle stimulation on the pain threshold was investigated. Pain perception was measured as the squeak threshold to noxious electric pulses. After cessation of the stimulation, an analgesic response was elicited within 60 min and peak analgesia developed after 120 min, being 139 +/- 10% (P less than 0.01) of the prestimulatory control value. The increased pain threshold lasted for another 2 h. One group of SHR was pretreated with PCPA, a serotonin synthesis blocker, which completely abolished the post-stimulatory analgesia. To analyse further the involvement of different serotonin systems, drugs with selective affinity for 5-HT receptors were used. In one group a prestimulatory dose of metitepine maleate (a 5-HT1&2 receptor antagonist) abolished the post-stimulatory elevation of the pain threshold. The prolonged analgesic response was still present after prestimulatory treatment with ritanserin or ICS 205-930 (5-HT2 and 5-HT3 blocking agents respectively). In another group of experiments, the serotonin receptor antagonists were administered post-stimulation to animals with fully elicited analgesia. None of the antagonists used could reverse the elevation of pain threshold towards prestimulatory levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors. 213 3

The present study examined the analgesic effects of the serotonin 5-HT3 receptor antagonists ICS-205-930, MDL-7222 and GR-38032F in mice using acute thermal, mechanical and chemical pain tests. Subcutaneous administration (1-10 mg/kg) of these agents did not produce analgesia in either the thermal or mechanical pain tests. However, ICS-205-930, MDL-72222 and GR-38032F all produced dose-dependent analgesia in the chemical pain test, that was not altered by systemic naloxone administration (1 mg/kg, s.c.). Intracerebroventricular administration of these drugs (0.1-10 micrograms) was ineffective in producing analgesia in acute thermal, mechanical and chemical pain tests. These results suggest that peripheral 5-HT3 receptors play a role in chemical, but not thermal or mechanical nociceptive mechanisms.
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PMID:Differential analgesic actions of serotonin 5-HT3 receptor antagonists in the mouse. 252 2

The antinociceptive properties of intrathecally (i.t.) administered [D-Ala2, N-methyl-Phe4, Gly5-ol]enkephalin (DAMPGO) and [D-Pen2, D-Pen5]enkephalin (DPDPE), selective opioid agonists for mu (mu) and delta (delta) sites, respectively, were compared in rats. DAMPGO and DPDPE elevated tail-flick latency (TFL) in a dose-dependent manner, and the spinal antinociceptive actions of both drugs were reversed by the opiate antagonist naloxone. These findings suggest that both DAMPGO and DPDPE interact with spinal opiate receptors to elevate TFL. Another set of experiments was done to determine the involvement of local spinal serotonin (5-HT) or norepinephrine (NE) in DAMPGO and DPDPE-induced spinal analgesia. Both the alpha 1 noradrenergic receptor antagonist WB-4101 and the alpha 2 blocker yohimbine failed to alter the antinociceptive actions of DAMPGO and DPDPE. Similarly, the 5-HT receptor antagonists pindolol, ritanserin and ICS 205-930 (selective for 5-HT1, 5-HT2 and 5-HT3 sites, respectively) failed to inhibit opioid-induced spinal analgesia. Thus, while DAMPGO and DPDPE produce antinociception via an interaction with spinal opioid receptors, apparently neither drug activates endogenous monoaminergic systems.
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PMID:A comparative analysis of monoaminergic involvement in the spinal antinociceptive action of DAMPGO and DPDPE. 255 89

beta-Endorphin administered intrathecally (i.t.) in rats produced a dose-dependent elevation in tail-flick latency. Naltrexone administered i.t. as a pretreatment reversed the spinal antinociceptive action of beta-endorphin, suggesting that the opioid interacts directly with spinal opiate receptors. Spinal administration of the alpha 1-adrenoceptor antagonist WB-4101 failed to alter the analgesic effects of the opioid, whereas the alpha 2-adrenoceptor antagonist yohimbine completely blocked beta-endorphin-induced elevations in tail-flick latency. Thus, there is an apparent specificity for the alpha 2-adrenoceptor to mediate the spinal action of beta-endorphin. The 5-HT1 and 5-HT3 receptor antagonists (spiroxatrine and ICS 205-930, respectively) also reversed the analgesic effects of the opioid, while the 5-HT2 receptor antagonist ritanserin only partially blocked beta-endorphin-induced elevations in tail-flick latency. The present results suggest that beta-endorphin produces analgesia at the spinal level via an opiate receptor-mediated interaction with spinal monoaminergic nerve terminals.
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PMID:Spinal beta-endorphin analgesia involves an interaction with local monoaminergic systems. 256 5

Intraplantar administration of serotonin 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 (1-100 micrograms; 50 microliters) produced dose-related analgesia against formalin-induced acute- and Freunds adjuvant-induced chronic-inflammatory pain in rats. 5-HT3 receptor antagonists had greater effect in the chronic pain test than in the acute paradigm. In both tests, ICS 205-930 was more potent than MDL 72222. These data further support the involvement of peripheral 5-HT3 sites in inflammatory pain, and suggest the utility of selective 5-HT3 receptor antagonists as peripheral analgesics.
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PMID:Peripherally administered serotonin 5-HT3 receptor antagonists reduce inflammatory pain in rats. 261 65

Intracerebroventricular (i.c.v.) injection of highly selective mu opioid receptor agonist ohmefentanyl (OMF) to rats produced dose-dependent antinociception as assessed with the tail flick test. This analgesia could be blocked by intrathecal (i.t.) injection of the 5-HT1A receptor antagonist spiperone or the 5-HT1C/2 receptor antagonist mianserin, but not by the 5-HT2 receptor antagonist 1-NP or the 5-HT3 receptor antagonist ICS 205-930. The results suggest that the descending 5-HT system is involved in mediating spinal mu opioid analgesia via spinal 5-HT1A and 5-HT1C/2 receptors.
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PMID:Spinal serotonin IA and IC/2 receptors mediate supraspinal mu opioid-induced analgesia. 769 28


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