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F V Abbott

Publications and source records attributed to F V Abbott.

At least 37 records · Page 2Linked to original sources
PubMed1990

beta-Funaltrexamine antagonizes the analgesic effects of mu and kappa agonists in the formalin test.

The formalin test assesses the behavioral response of an animal to minor tissue injury-induced pain. Opioid antinociception in this test has been suggested to depend largely on activation of kappa receptors but mu agonists are also potent in reducing pain behavior. The present study used the irreversible mu antagonist, beta-funaltrexamine (beta-FNA), to examine the role of mu receptor activation in this test. beta-FNA given intracranially 4 h before testing fully blocked the effects of morphine and attenuated the effects of ethylketocyclazocine and U50,488H. The results do not support a role for kappa receptors in antinociception in the formalin test. Instead, mu and, possibly, delta receptors are involved.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Activation of central mu-opioid receptors is involved in clonidine analgesia in rats.

The analgesic effect of clonidine in spontaneously hypertensive rats (SHR) and in normotensive Sprague-Dawley (SD) rats was assessed by using the formalin pain test. The analgesic response of SD rats to low doses (15-60 micrograms/kg i.p.) but not to a high dose (150 micrograms/kg i.p.) of clonidine was inhibited by naloxone, 2 mg/kg i.p., and similar interaction was noted in SHR. In both rat strains, the analgesic response to low i.p. doses of clonidine was also inhibited by injection of 5 micrograms of naloxone or 7 micrograms of beta-funaltrexamine, a mu-receptor antagonist, into the lateral cerebral ventricle. I.c.v. injection of 5 micrograms of ICI 174864, a delta-receptor antagonist, potentiated or did not influence clonidine analgesia in SD rats and SHR, respectively. It is concluded that the analgesic response to clonidine involves activation of central mu-opioid receptors in both SHR and SD rats, possibly by an endogenous opioid released by clonidine.

Analgesia↗
PubMed1988

Peripheral and central antinociceptive actions of ethylketocyclazocine in the formalin test.

The antinociceptive actions of ethylketocyclazocine and morphine were examined in rats in a thermal nociceptive test (tail-immersion) and a test involving minor tissue injury (formalin). In the formalin test, the antinociceptive effects of high doses of ethylketocyclazocine, but not morphine, were attenuated by the peripherally acting antagonist naloxone methylbromide. Naloxone methylbromide had no effect on antinociception produced by ethylketocyclazocine in the tail-immersion test. When ethylketocyclazocine was injected intraventricularly, only partial antinociception was observed in the formalin test. Conversely, naloxone given intraventricularly only partially attenuated the antinociception produced by ethylketocyclazocine given systemically. The data indicate that the antinociceptive effects of ethylketocyclazocine in the tissue injury-induced nociception are a result of summation of central and peripheral actions. Morphine antinociception reaches ceiling at doses that are devoid of such peripheral actions. The data imply that it may be possible to develop a new class of peripherally acting analgesics that are effective in acute inflammatory pain.

Analgesics↗
PubMed1988

Morphine-6-glucuronide: analgesic effects and receptor binding profile in rats.

The antinociceptive effects of morphine-6-glucuronide (M6G) were examined in two animal models of pain, the tail immersion test (reflex withdrawal to noxious heat) and the formalin test (behavioral response to minor tissue injury). In the tail immersion test, M6G produced an increase in withdrawal latency that rose rapidly between 0.01 and 0.025 ug ICV or 1 and 2 mg/kg SC. A further increase occurred at doses greater than 0.2 ug ICV or 4 mg/kg SC and was associated with marked catalepsy and cyanosis. Naloxone, 0.1 mg/kg SC, shifted the lower component of the dose-effect relation by a factor of 24. In the formalin test, 0.01 ug M6G ICV produced hyperalgesia, while between 0.05 and 0.2 ug ICV, antinociception increased rapidly without toxicity. The dose effect relations for hyperalgesia and antinociception were shifted to the right by factors of 20- and 3-fold, respectively. By comparison, ICV morphine was 60 (formalin test) to 145-200 (tail immersion test) times less potent than M6G. At sub-nanomolar concentrations, M6G enhanced the binding of [3H]-etorphine, [3H]-dihydromorphine and [3H]-naloxone to rat brain membrane receptors by 20-40%. At higher concentrations, M6G displaced each ligand from binding sites, with Ki values of about 30 nM, as compared to morphine Ki values of about 3 nM. The data indicate that the in vivo and in vitro effects of M6G are complex and that M6G may play an important role in analgesia in experimental animals, and by implication, in man.

Analgesics↗
PubMed1988

Effect of 5-hydroxytryptamine precursors on morphine analgesia in the formalin test.

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.

5-Hydroxytryptophan↗
PubMed1987

Endorphinergic mechanism in the central cardiovascular and analgesic effects of clonidine.

In urethane-anesthetized male rats, injection of 5 nmol clonidine into the nucleus of the solitary tract (NTS) causes hypotension and bradycardia. These effects are greater in spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley (SD) rats than in normotensive Wistar-Kyoto (WKY) rats. The effects of clonidine are stereoselectively inhibited by 100 ng intra-NTS naloxone in SHR and SD but not in WKY rats. In SHR, the effects of clonidine are also inhibited by intra-NTS administration of ICI 174864 (a delta-receptor antagonist) but not by beta-funaltrexamine (a mu-receptor antagonist), while in SD rats only the mu- and not the delta-antagonist was effective. Neonatal treatment of SHR with monosodium glutamate (MSG) reduced the beta-endorphin content of the arcuate nucleus and the NTS, reduced the cardiovascular effects of clonidine, and abolished their naloxone sensitivity. MSG treatment of newborn WKY reduced the beta-endorphin content of the arcuate nucleus but not the NTS and did not affect the responses to clonidine. Measurement of pain sensitivity by the formalin test indicated that clonidine was more potent as an analgesic in SHR and SD than in WKY rats, and its effect was inhibited by naloxone (2 mg/kg i.p.) in the former two strains but not in WKY. It is proposed that a naloxone-sensitive component of the cardiovascular effects of clonidine is due to release of a beta-endorphin-like opioid from the NTS, and that this mechanism is present in SHR and SD but not in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1986

A dose-ratio comparison of mu and kappa agonists in formalin and thermal pain.

The effects of putative mu and kappa agonists, with and without naloxone, were compared in the formalin and tail flick tests in rats. The mu agonist sufentanil was more potent in the tail flick test than the formalin test while the opposite was true for the kappa agonist ethylketocyclazocine (EKC). MR2034 was equipotent in the two tests and in the tail flick test, analgesia decreased at high doses. The naloxone (0.1 mg/kg) dose-ratios (DR) for sufentanil and EKC were 3 to 7 times larger for the tail flick test than the formalin test. From this and other DR studies it is argued that in thermal pain tests, opioid analgesia is mediated primarily by mu receptors while in non thermal tests kappa effects predominate.

Analgesia↗
PubMed1986

The stress of a novel environment reduces formalin pain: possible role of serotonin.

Compared to rats that were given three daily sessions of habituation to a laboratory environment, non-habituated rats were behaviourally less reactive when pain was produced by 0.05 ml of 2.5% formalin injected s.c. in one hindpaw. This behavioural analgesia was equivalent to that produced by approximately 2.0 mg/kg morphine and was interpreted as analgesia induced by the stress of exposure to a novel environment. Methysergide (10 mg/kg) or 1-valine (200 mg/kg) alone, or combined with naloxone (0.1 or 2.0 mg/kg), reversed the effect of exposure to a novel environment. Naloxone itself had no significant effect. In habituated rats 1-valine reduced the response to formalin-induced pain whereas methysergide combined with naloxone increased it. It is concluded that analgesia induced by the stress of exposure to a novel environment depends on serotonin.

Animals↗
PubMed1986

Qualitative differences in effects of opioids in man: preliminary evidence for multiple mechanisms of analgesic action.

The analgesic effects of meperidine, anileridine, codeine and codeine + acetominophen on surgical and non-surgical pain in 101 patients were assessed using the McGill Pain Questionnaire. The quality of analgesia was determined by analyzing the changes in the pain descriptors chosen 1 hour after medication. Meperidine and anileridine differentially reduced pain qualities rated as "bright-phasic" by a student sample. Codeine and codeine + acetominophen produced similar patterns of analgesia that were homogeneous across "bright-phasic" and "dull-tonic" types of pain. The data suggest the possibility that opioids may differ in the quality of analgesia produced either as dose increases or different opioid receptor types are recruited.

Acetaminophen↗
PubMed1986

Noncompetitive antagonism of morphine analgesia by diazepam in the formalin test.

The effects of diazepam on morphine analgesia dose effect curves in the formalin test and in two forms of the tail flick test were examined. In one form of the tail flick test the animals were restrained in wire restrainers (a stressful procedure) while in the other they were left free and briefly handheld for testing. Morphine analgesia in the restrained form of the test is known to depend on raphe magnus 5HT projections to the spinal cord while the other tests do not involve this system. Diazepam (0.2 and 1.0 mg/kg) noncompetitively antagonized morphine analgesia in the formalin test but had no effect on morphine analgesia in the tail flick test. It is concluded that diazepam does not antagonize morphine analgesia through its antianxiety action reducing the serotonergic response to stress. It is suggested that the sensitivity of the formalin test to diazepam antagonism of morphine analgesia may be of clinical significance since formalin test pain resembles postoperative pain in humans.

Animals↗
PubMed1985

Naloxone reverses the antinociceptive action of clonidine in spontaneously hypertensive rats.

Earlier studies have shown that the antihypertensive action of clonidine is reversed by naloxone in hypertensive (SHR), but not in normotensive rats (WKY). We investigated the effects of clonidine and naloxone on pain sensitivity of SHR and WKY by using the formalin test (FT) and the tail-flick test (TFT). Using the FT, basal pain sensitivity was similar in SHR and WKY. Clonidine produced dose-dependent analgesia (0.03-0.15 mg/kg i.p.), and it was more potent in SHR than in WKY. The effect of clonidine was partially antagonized by naloxone (2 mg/kg i.p.) in SHR, but not in WKY. Naloxone alone caused moderate analgesia in SHR and no effect in WKY. Using the TFT, SHR displayed a naloxone-reversible decrease in basal pain sensitivity, when compared to WKY. Clonidine was ineffective (WKY) or caused moderate hyperalgesia (SHR). These results indicate that the two pain tests activate different pain controlling mechanisms, with different sensitivity to the antinociceptive action of clonidine. In SHR, this action seems to involve the release of endogenous opioids.

Analgesia↗
PubMed1984

Unilateral analgesia produced by intraventricular morphine.

Morphine injected into the lateral ventricle of the rat produced unilateral analgesia in the formalin test, which involves continuous, moderate pain. In contrast, analgesia was produced bilaterally in the foot-flick test which involves brief, rapidly rising pain. In the formalin test, intraventricular morphine produced analgesia in the ipsilateral but not the contralateral hindpaw. Analgesia was achieved with relatively low doses of morphine (2.5-10.0 micrograms) in the formation test while very high doses (50-200 micrograms) were necessary to produce analgesia in the foot-flick test. These results add to other data indicating that different neural mechanisms underlie opiate analgesia in different types of pain. Moreover, they indicate that, in the formation test, the neural mechanisms of morphine analgesia are somatotopically organized and that forebrain structures are likely to be involved.

Animals↗
PubMed1984

Behavioral evidence in rats for a peptidergic-noradrenergic interaction in cutaneous sensory and vascular function.

Cutaneous sensory and vascular function was examined following application of capsaicin to the sciatic nerve and systemic injection of guanethidine. Together the two drugs produced a reduction in sensitivity to heat-pain, inflammatory pain (formalin test), tactile stimulation and skin temperature of the foot that exceeded the effects of either drug alone. The inflammation produced by an injection of formalin to the plantar surface of the hind paw was reduced equally by capsaicin or capsaicin + guanethidine. Cold sensitivity and inflammation produced by yeast injection were unaffected by all treatments. The data imply a peripheral interaction between peptidergic and noradrenergic systems with significant functional implications that may be important in the pathology of familial dysautonomia.

Animals↗
PubMed1984

Single nerve capsaicin: effects on pain and morphine analgesia in the formalin and foot-flick tests.

Application of capsaicin to the sciatic nerve reduces responsiveness to pain in the foot-flick test which examines brief, threshold-level pain. The purpose of the present study was to determine if a similar reduction occurs in the formalin test which examines suprathreshold, deep pain that persists for several hours. The sciatic nerve on one side in the rat was exposed and soaked for 15 min in a solution of capsaicin and the saphenous nerve was ligated and cut. The operated foot was tested for sensitivity to pain in the formalin and foot-flick tests 2 days to 12 weeks later both with and without morphine. The capsaicin treatment produced a substantial reduction in sensitivity to foot-flick heat pain at all times after surgery. In the formalin test, the effects were small and tended to suggest that the rats felt more rather than less pain. The capsaicin treatment markedly reduced the sensitivity of formalin test pain to morphine. This effect appeared about one week after surgery and persisted for 12 weeks. The results suggest that capsaicin-sensitive unmyelinated afferents play a role in the threshold-level, non-damaging heat pain, but are not involved in pain resulting from tissue damage. However, these afferents appear to be important for the spinal action of morphine on this type of pain.

Analgesia↗
PubMed1982

Brainstem lesions dissociate neural mechanisms of morphine analgesia in different kinds of pain.

The effects of brainstem lesions on morphine analgesia were examined using the formalin test which produces moderate pain that lasts about 2 h, and the tail-flick test which measures brief threshold-level pain. Lesions of the nucleus raphe magnus attenuated and small lesions of the central tegmental nucleus potentiated the effects of morphine in the tail-flick test. Lesions of the median raphe nucleus potentiated the effects of morphine in the formalin test. Large lesions of the pontine reticular formation had no effect in either pain test. These results indicate that the neural mechanisms underlying morphine analgesia are different in different kinds of pain.

Analgesia↗
PubMed1982

Morphine analgesia and tolerance in the tail-flick and formalin tests: dose-response relationships.

The dose-response relationships for morphine analgesia were studied in morphine-tolerant and non-tolerant rats using two pain tests: the tail-flick test which measures the threshold for an escape response, and the formalin test which assesses the behavioral response to continuous pain generated in injured tissue. The effects of prior experience with both pain tests on tolerance were also examined. In the formalin test, effective analgesia was obtained in non-tolerant rats at doses that produce minimal depression of locomotor behavior. Morphine tolerance was produced by 20 daily injections of morphine with increments that reached 16 mg/kg, a dose over the LD100 for barrier sustained Long Evans rats. This dose regimen produced a 1.8-fold increase in the ED50 in the tail-flick test and a 2.7-fold increase in the formalin test. Daily experience of the pain test, as well as the morphine regimen produced a 4.8-fold increase in the ED50 in the tail-flick test but did not affect the potency of morphine in the formalin test. The magnitude of tolerance in the absence of daily behavioral testing is consistent with recent clinical reports that little tolerance occurs after prolonged administration of morphine in cancer patients and that tolerance is not an important consideration in the management of pain.

Animals↗
PubMed1981

Apparent lack of tolerance in the formalin test suggests different mechanisms for morphine analgesia in different types of pain.

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.

Animals↗