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)

Substance P produces analgesia when administered to mice in very small doses by the intraventricular route (1.25 to 5 nanograms per mouse). The analgesic effect can be blocked by naloxone. At higher doses (greater than 50 nanograms per mouse), this activity is lost. At these higher doses, however, substance P produced hyperalgesia when combined with naloxone and analgesia when combined with baclofen [beta-(4-chlorophenyl)-gamma-aminobutyric acid]. Substance P may have dual actions in brain, releasing endorphins at very low doses and directly exciting neuronal activity in nociceptive pathways at higher doses.
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PMID:Dual actions of substance P on nociception: possible role of endogenous opioids. 20 12

The antinociceptive and hypothermic effects of intracisternal administration of 11 endogenous neuropeptides and morphine were evaluated in mice. Of the substances tested, only neurotensin (NT) and beta-endorphin exerted significant antinociceptive and hypothermic effects; NT was the most potent in inducing hypothermia whereas beta-endorphin was the most potent antinociceptive agent via this route of administration. Both NT, and beta-endorphin were, on a molar basis, considerably more potent antinociceptive agents than morphine, [Met]enkephalin, or [Leu]enkephalin. NT-induced analgesia and hypothermia both were significantly dose-dependent. Substance P was found to produce significant hyperalgesia and hyperthermia. Bombesin produced a significant hypothermic effect, whereas somatostatin and luteinizing hormone-releasing hormone (luliberin) produced hyperthermia. None of the other peptides studies [bradykinin, thyrotropin-releasing factor (thyroliberin), melanocyte-stimulating hormone release-inhibiting factor (melanostatin), somatostatin, [Met]enkephalin, and [Leu]enkephalin] produced any significant alterations in colonic temperature or response to a noxious stimulus with the doses tested. These data demonstrate that NT and beta-endorphin, two endogenous brain peptides, are potent in inducing hypothermia and in producing an antinociceptive state.
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PMID:Alterations in nociception and body temperature after intracisternal administration of neurotensin, beta-endorphin, other endogenous peptides, and morphine. 29 52

Substance P (SP), released from thin afferent terminals, is believed to be a neurotransmitter for pain transmission in the spinal dorsal horn. It has been demonstrated that in addition to analgesia, morphine increases the accumulation of SP possibly due to the inhibition of its release. The present work investigated the level of spinal SP like immunoreactivity (SPLI) following electroacupuncture analgesia in rats using immunohistochemistry and image analysis. Experiment results revealed that formalin injected into the hind paw elicited marked pain response and accumulation of SP in the spinal dorsal horn. Electroacupuncture of Tsu-San-Li could depress the pain response, however increasing further the SP accumulation. It is thus suggested that pain stimulation itself may activate the endogenous opioid mechanism to inhibit SP release and acupuncture is able to enhance the process. This may be one mechanism of acupuncture analgesia.
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PMID:Alterations of spinal dorsal horn substance P following electroacupuncture analgesia--a study of the formalin test with immunohistochemistry and densitometry. 137 50

Substance P (SP) is a non-opioid peptide that generates a potent analgesia when injected into the periaqueductal gray matter (PAG). The aim of this study was to investigate the fine neuronal structures and synaptic circuits involved in SP action in rats by means of electron microscopy, using immunocytochemical (ICC) pre-embedding methods. A conventional ultrastructural study, carried out to interpret the ICC data correctly, shows small sized nerve cell bodies with a high nucleus-cytoplasmic ratio; absence of an extensive granular endoplasmic reticulum; and few axo-somatic contacts having symmetrical and asymmetrical junctions in equal proportions. The large neuropil is characterized by numerous thin unmyelinated axons and axo-dendritic synapses mainly showing pleomorphic vesicles and asymmetrical junctions. The ICC analysis showed moderately labeled nerve cell bodies with the same structural, synaptic, and dimensional features as the negative cells. In the neuropil SP immunoreactivity is shown by dendrites, synapses, and thin elements which are unidentifiable structurally. No SP terminals synapsing on SP nerve cell bodies were found and only occasional SP light labeled terminals synapsing on negative perikarya were seen. The SP boutons generally have pleomorphic vesicles and asymmetrical junctions. On the basis of these data a possible excitatory activity of PAG SP synapses could be hypothesized. This activity would take place on postsynaptic neurons generally at a dendritic level. Our ultrastructural findings give support to an excitatory role carried out by SP neurons of the PAG, as suggested by the role of PAG circuitry on spinal nociception.
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PMID:Ultrastructure of substance P immunoreactive elements in the periaqueductal gray matter of the rat. 170 83

The change in the nociceptive reactions of rats was characterized after stressful acoustic (115 dB) stimulation. Acoustic loading for five minutes resulted in considerable analgesia in the hot-plate test, whereas a significant analgesic response was not observed in the tail-flick test. The analgesic reaction after acoustic stimulation was resistant to naloxone pretreatment and was also found in morphine-tolerant rats, but the acute thermoregulatory and analgesic effects of morphine were greatly potentiated by simultaneous acoustic loading. Substance P or cholecystokinin treatment likewise failed to prevent the analgesic effect of auditory stimulation. No tolerance developed to the analgesic effect on repeated stressing. Diltiazem, a slow calcium channel blocker, facilitated the analgesia. The data suggest a stress-induced analgesia with obviously non-opiate properties, although an indirect involvement of opiate effects could not be excluded.
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PMID:Non-opiate analgesia following stressful acoustic stimulation. 241 94

Substance P (SP) injected into intraspinal (i.s.) spaces caused mice to vigorously scratch and bite their skins in an apparent reaction to a perceived cutaneous sensation. The scratching behavior was similar to the reciprocal hindlimb-scratching syndrome (RHS) described for intracranial (i.c.) SP injections. Radiotracer experiments, as well as potency and latency measurements, demonstrated that SP-induced scratching, whether induced by the i.c. or i.s. route, was due to SP receptor stimulation in the cervicothoracic cord. Similarly, biting was due to SP stimulation of the lumbosacral spinal cord. Mice coated with capsaicin, an irritant chemical, scratched and bit the coated areas in a manner similar to animals injected with i.s. SP. Standard analgesics depressed this scratching behavior elicited by topical capsaicin. Non-analgesic drugs, with the exception of amphetamine, did not affect capsaicin-induced pain. It is concluded that i.s. SP induces a painful sensory experience. Some piperazinone derivatives of substance P's C-terminal hexapeptide are shown to specifically antagonize the scratching induced by i.s. SP with little or no effect on motor behavior. These antagonists depressed scratching elicited by topical capsaicin and were analgesic on the hot-plate test. It is concluded that SP is a natural neurotransmitter for pain and that antagonism of endogenous SP systems causes analgesia.
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PMID:Analgesic activities of spinal cord substance P antagonists implicate substance P as a neurotransmitter of pain sensation. 242 37

Peptides with hormonal or neuronal activity are derived by enzymatic processing from pro-hormones, which by themselves are biologically inert. Processing and other enzymatic conversions may occur step-wise, leading to the formation of a cascade of biologically active (or inactive) peptides. The neurokin in substance P is known to be metabolically transformed both by amino- and endopeptidases. More N-terminal substance (1-7) has been found than C-terminal (2-11 to 5-11) fragments in various CNS areas. The substance P (1-7) fragment also shows biological activity e.g., providing analgesia, lowering blood pressure, inhibiting aggressive behavior and (in contrast to substance P) inhibiting grooming behavior. An endopeptidase generating substance P (1-7) and to a lesser extent, substance (1-8), has been isolated and characterized from human cerebrospinal fluid (CSF) and bovine spinal cord, as a metalloenzyme with essential SH-groups. Substance P co-exists with calcitonin gene related peptide (CGRP) in a large population of non-myelinated primary afferent ('pain') fibers. Intrathecal injection of substance P causes behavioral and physiological responses which are potentiated and prolonged by CGRP. It was found that CGRP competes with substance P for the endopeptidase. It is suggested that the main action of CGRP in the spinal cord is to inhibit substance P degradation.
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PMID:Modulation of endopeptidase activity by calcitonin gene related peptide: a mechanism affecting substance P action? 245 90

Substance P (SP) injected intracerebroventricularly (ICV) into rabbits caused dose-related thermal analgesia with the maximum effect after 2 micrograms. The analgesia was measured by timing the withdrawal of the rabbit's ear from an infrared beam. Equimolar amounts of the related peptides physalaemin and eledoisin-related peptide also caused analgesia, but the SP N-terminal fragment (1-9) was inactive. This suggests that the analgesic message of SP resides within the C-terminal fragment. The analgesia caused by each peptide developed more rapidly but did not last as long as that after central injection of beta-endorphin. In separate experiments, 2 micrograms SP injected ICV increased blood pressure and decreased heart rate. The analgesic, bradycardic and pressor responses to central administration of SP were opposite to effects of peripherally administered SP, described previously. These results indicate that the effect induced by SP depends upon its specific neuroanatomical site of action.
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PMID:Analgesic and cardiovascular effects of centrally administered substance P. 245 73

A method for assessing inflammatory pain response was developed by modification of the formalin test. Formalin (0.5%, 25 microliters) was injected into the hindpaw of the mouse, and the durations spent in licking or biting response were measured as an indicator of pain response. The response curve was biphasic, having two peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). Morphine, ethylketocyclazocine, ketocyclazocine and pentazocine inhibited the response dose-dependently at the first and the second phases. Aspirin, oxyphenbutazone and dexamethasone inhibited only the second phase. Aminopyrine and mefenamic acid which acted at both central and peripheral sites inhibited both phases; however, the inhibition of the second phase was stronger than that of the first phase. Substance P (SP) antagonist inhibited only the first phase. Bradykinin (BK) inhibitor caused a inhibition of both first and second phases, and pretreatment of compound 48/80 and indomethacin inhibited only the second phase. From these facts, it was suggested that SP and BK played a role in the pain response at the first phase, and histamine, BK and PG were involved at the second phase. Naloxone produced hyperalgesia and bestatin produced analgesia at the second phase; then, it seems that the endogenous opioid system is activated by formalin stimulation and modulates the pain perception. Based on these findings, it is presumed that the pain of the first phase is evoked by the direct stimulation of the nerve fibers, and that of the second phase is due to the inflammatory reaction.
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PMID:[Studies of inflammatory pain response: related pain producing substance and endogenous opioid system]. 372 60

Noxious stimulus-induced changes in substance P (SP) release in the dorsal horn of the spinal cord and met-enkephalin release in the brain stem were investigated. For this purpose, a specially devised push-pull cannula system was used. Noxious stimuli were applied to the skin of the hind paw of rabbits and the lumbar dorsal horn was perfused using a push-pull cannula. Substance P concentration in the perfusate was assayed by radioimmunoassay. Noxious mechanical stimuli, but not thermal stimuli, increased the release of immunoreactive substance P (iSP). Innocuous stimuli did not affect the release of these peptides. Systemic administration of an analgesic dose of morphine (1 mg/kg) did not inhibit the iSP release induced by noxious stimuli. This suggests that morphine analgesia may not be mediated by a blocking action on SP release from the primary afferent terminals at the dorsal horn. The nucleus reticularis gigantocellularis (NRGC) of rat medulla oblongata was perfused in situ and the effects of noxious stimuli on the release of immunoreactive met-enkephalin were examined. Formalin and thermal stimuli, but not mechanical stimuli, increased the "tonic" release of immunoreactive met-enkephalin from NRGC. No "phasic" increase was observed following the three forms of stimulation. Topical application of dibucaine abolished the formalin-induced increase in the release of met-enkephalin. Therefore, the possibility that persistent noxious stimuli may activate the met-enkephalin-containing fibers in the NRGC must be given consideration.
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PMID:Experimental pain and neuropeptides. 608 33


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