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)

Nociceptive response induced by 0.5% Formalin in the hindpaw of mice had two peaks, 0-5 min (first phase) and 15-20 min (second phase). By using the distinct biphasic response, the nature of the transmitter systems activated by Formalin in the spinal cord was studied for the purpose of determining the difference of the role of substance P (SP) and somatostatin (SST). The injection of (D-Pro2, D-Trp7,9)SP, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP and SP antiserum inhibited only the first phase response. The i.t. injection of -Aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr- (an SST antagonist), SST antiserum and cysteamine (an SST depletor) inhibited only the second phase. This result indicates that SP is involved in the transmission of the first phase, and SST is involved in the transmission of the second phase of the Formalin-induced nociceptive response. With regard to other nociceptive stimuli, two i.t. SP antagonists produced a significant analgesia in the hot plate and tail pinch tests but had no effect in the acetic acid writhing test. However, i.t. SST antagonist and cysteamine produced a significant analgesia in the writhing test but had no effect in the hot plate and tail pinch test. These results suggest that SP participates in the transient pain induced by such acute stimuli as hot plate, tail pinch and the first phase of Formalin response and that SST participates in the prolonged and inflammatory pain induced by stimuli such as acetic acid and the second phase response.
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PMID:Roles of substance P and somatostatin on transmission of nociceptive information induced by formalin in spinal cord. 169 Aug 1

The 5-hydroxytryptamine (5HT) precursors tryptophan and 5-hydroxytryptophan had no significant effect on the behavior of rats in the formalin test when given by themselves. However, both compounds significantly attenuated the analgesic effect of morphine in the formalin test. The 5HT antagonist methysergide enhanced the antinociceptive effect of morphine but systemic 5HT had no effect. Assays of whole brain and spinal cord indoles revealed different patterns as a result of tryptophan or 5-hydroxytryptophan loading. The effect common to both treatments was an increase in brain 5HT. There was no effect of morphine on any measure. Formalin injection by itself did not alter indole levels in the brain or spinal cord. Our results, taken in conjunction with previous work, suggest that 1) 5HT in the spinal cord does not influence pain perception in the formalin test and 2) 5HT in the brain can antagonize morphine analgesia in the formalin test. We conclude that there may be circumstances in which the use of 5HT precursors for clinical pain management may be contraindicated.
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PMID:Effect of 5-hydroxytryptamine precursors on morphine analgesia in the formalin test. 247 42

Three opioid agonists ([D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and U50488H) were tested independently for their ability to produce analgesia in the formalin test. These agonists were chosen based upon their ability to act selectively at mu, delta and kappa opioid receptor types respectively. Rats received one intracerebroventricular (i.c.v.) injection of an agonist 20 min after subcutaneous injection of 15% formalin into a rear paw. Formalin injection produces continuous pain that results in two stereotypic behaviors, paw licking and paw lifting. Ten minutes after i.c.v. injection rats were observed for an 8 min period and scored for formalin-induced behavior. All agonists produced analgesia as indicated by a dose-dependent attenuation of formalin-induced behavior. At the doses tested, the rank order of analgesic efficacy was DAGO greater than DPDPE greater than U50488H. We suggest that centrally located mu, delta and kappa opioid receptors can each modulate the perception of this clinically relevant form of continuous pain. Additionally, the highest dose of DPDPE tested significantly increased rearing whereas DAGO and U50488H failed to affect rearing.
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PMID:Analgesia produced by centrally administered DAGO, DPDPE and U50488H in the formalin test. 321 76

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

Evoked compound-action potentials (cAP) in all three fibre types of the isolated nerve were reversibly depressed by exposure to the drugs. After 20 min exposure, lidocaine (0.5 mM) depressed the amplitude of the A and B fibre potentials significantly more than the C fibre potential. With eugenol (0.8 mM), there was no significant difference in depression of A, B and C fibre activity. With formaldehyde (4.5 mM), the latency was longer, and the C fibres were initially significantly more depressed than the A and B fibres. As dull pain from a chronically-inflamed pulp is believed to be mediated through C fibres, these results may explain the difficulties in obtaining complete local analgesia with lidocaine. They indicate that application of low concentrations of eugenol and formaldehyde to the pulp-dentine organ may have an analgesic effect on pain mediated through both A and C fibres.
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PMID:Differential inhibition of A, B and C fibres in the rat vagus nerve by lidocaine, eugenol and formaldehyde. 386 54

Extracellular single-unit recordings were made in nucleus raphe magnus in unanesthetized, unrestrained cats. Discharge of serotonergic neurons in this region was increased when animals were aroused by noxious stimuli such as pinch and radiant heating of the tail, but these cells were not specifically nociceptive. Peristimulus time histograms indicated that stimulation in the periaqueductal gray was excitatory but alveolar nerve stimulation at a noxious current intensity was no more effective than nonnoxious nerve stimulation in activating serotonergic unit discharge: Similarly, stressful treatments such as physical restraint increased the discharge of some serotonergic neurons, but these cells were activated during any period of behavioral arousal whether or not arousal was the result of aversive treatment. Injection of Formalin into the paw produced pain lasting about 30 min without increasing serotonergic unit discharge above rates observed during undisturbed active waking behavior. The activity of serotonergic neurons was not increased by an analgesic dose of morphine (2 mg/kg, i.p.). These results then are not consistent with the hypothesis that morphine analgesia depends on activation of serotonergic neurons in nucleus raphe magnus or that these cells are specifically involved in modulation of nociception. These neurons may, however, be involved in nociceptive control within the context of a general modulation of sensorimotor processes by serotonin in the central nervous system. We did observe neurochemically unidentified neurons in the medulla whose discharge was more specifically activated by aversive stimuli and also by morphine. It is possible that these neurons are more directly involved in the mediation of opiate and/or stress-induced analgesia.
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PMID:Response of serotonin-containing neurons in nucleus raphe magnus to morphine, noxious stimuli, and periaqueductal gray stimulation in freely moving cats. 399 12

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

To determine whether opioid peptide-receptor pharmacological association found in vitro (e.g., enkephalin-delta, dynorphin-kappa) predict anatomical relationships in situ, immunocytochemical and receptor autoradiographic studies were carried out on adjacent sections from the same brains of formaldehyde-perfused rhesus monkeys. Apparent mu and kappa opioid receptors (labeled, respectively, by [3H] naloxone and [3H]bremazocine under different incubation conditions), but not delta opioid receptors (labeled by [3H]D-Ala2, D-Leu5-enkephalin), survived the fixation procedure, and were found to be colocalized throughout the brain. We have observed complex associations between these binding sites and one, two, or all three opioid peptide systems (i.e., proopiomelanocortin, proenkephalin, and prodynorphin) in different brain regions. These multiple opioid peptide-receptor subtype associations are apparent, for example, in neural systems involved in the processing of pain stimuli, and may be important for mediating different types of analgesia. Since differential processing of proenkephalin and prodynorphin can give rise to opioids of varying receptor selectivities, the colocalization of opioid receptor subtypes may signify that such processing is a key regulatory event in determining which receptor subtype is activated and, thus, the physiological consequences of opioid neurotransmission.
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PMID:Anatomical relationship between opioid peptides and receptors in rhesus monkey brain. 615 4

The effects of several cholinergic and dopaminergic agents on pain and morphine analgesia were assessed using three pain tests. These tests--tail-flick, hot-plate, and Formalin--allow comparison of the effects of different noxious stimuli and different motor responses. Each pain test yielded a unique constellation of cholinergic and dopaminergic influences, suggesting that variation of stimulus and response parameters can change the functional expression of cholinergic and dopaminergic systems related to pain processing. Significant analgesia was observed in the Formalin test, compared with the saline control, after administration of choline (30 or 60 mg/kg), atropine (2 mg/kg), mecamylamine (2 mg/kg or 10 mg/kg), or apomorphine (0.3 or 8 mg/kg). No analgesic effects in this test were observed after atropine (10 mg/kg) or pimozide (0.125 or 0.5 mg/kg). In contrast, there was no evidence of analgesia produced by any of these drugs, in the doses given, in the hot-plate test, and only apomorphine (8 mg/kg) produced analgesia in the tail-flick test. When these cholinergic and dopaminergic agents were administered to rats after an injection of 2.5 mg/kg morphine, which by itself has been shown not to produce analgesia in any of the tests, a general pattern of facilitation was observed in the Formalin test but not in the tail-flick or hot-plate tests. Facilitation was produced by choline, atropine, mecamylamine, apomorphine, and pimozide (at 0.5 mg/kg but not 0.125 mg/kg). The data suggest that differences in the type of noxious stimulation and in the motor responses required in various pain tests are crucial in determining the observed pharmacologic profile of pain and opiate analgesia.
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PMID:Effects of cholinergic and dopaminergic agents on pain and morphine analgesia measured by three pain tests. 686 45

Tolerance to morphine analgesia was examined using the Formalin test in which pain lasting about 2 hrs associated with minor tissue injury is produced by subcutaneous injection of dilute Formalin. To distinguish behavioral from pharmacological tolerance, different groups of rats received their daily morphine injection (7 mg/kg) in the test environment or in their home environment for 5 days. Another group of rats was given morphine for 15 days in the home cage followed by 5 days in the test environment. None of the morphine injected groups differed from saline injected control groups in the amount of analgesia. These findings add to previous evidence that the Formalin test measures a type of pain which is different from that assessed in withdrawal reflex tests, and which more closely resembles clinical pain in man. Moreover, the fact that analgesia in the Formalin test shows little tolerance while analgesia in withdrawal tests shows rapid tolerance suggests that the underlying neural mechanisms are different.
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PMID:Apparent lack of tolerance in the formalin test suggests different mechanisms for morphine analgesia in different types of pain. 729 Dec 66


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