Biomedical subjects

A L Vaccarino

Publications and source records attributed to A L Vaccarino.

At least 19 recordsLinked to original sources

PubMed2001

Endogenous opiates: 2000.

This paper is the twenty-third installment of the annual review of research concerning the opiate system. It summarizes papers published during 2000 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunological responses.

Animals↗

PubMed2001

Central neuroplasticity and pathological pain.

The traditional specificity theory of pain perception holds that pain involves a direct transmission system from somatic receptors to the brain. The amount of pain perceived, moreover, is assumed to be directly proportional to the extent of injury. Recent research, however, indicates far more complex mechanisms. Clinical and experimental evidence shows that noxious stimuli may sensitize central neural structures involved in pain perception. Salient clinical examples of these effects include amputees with pains in a phantom limb that are similar or identical to those felt in the limb before it was amputated, and patients after surgery who have benefited from preemptive analgesia which blocks the surgery-induced afferent barrage and/or its central consequences. Experimental evidence of these changes is illustrated by the development of sensitization, wind-up, or expansion of receptive fields of CNS neurons, as well as by the enhancement of flexion reflexes and the persistence of pain or hyperalgesia after inputs from injured tissues are blocked. It is clear from the material presented that the perception of pain does not simply involve a moment-to-moment analysis of afferent noxious input, but rather involves a dynamic process that is influenced by the effects of past experiences. Sensory stimuli act on neural systems that have been modified by past inputs, and the behavioral output is significantly influenced by the "memory" of these prior events. An increased understanding of the central changes induced by peripheral injury or noxious stimulation should lead to new and improved clinical treatment for the relief and prevention of pathological pain.

Afferent Pathways↗

PubMed2000

Analgesic effects of endomorphin-1 and endomorphin-2 in the formalin test in mice.

Two recently isolated peptides, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), are highly selective micro-opioid receptor agonists with analgesic actions in the tail-flick test. To further assess the analgesic properties of these peptides, the effects of endomorphin-1, endomorphin-2, and morphine were examined in the formalin test. Male Swiss Webster mice were injected i.c.v. with endomorphin-1, endomorphin-2, or morphine (0, 1, 3, 10 microg) 5 min before injection of 20 microl of 5% formalin s.c. into the plantar surface of one hind-paw. The mice were observed for 60 min after formalin injection. Endomorphin-1 and endomorphin-2 produced dose-dependent analgesia that was shorter in duration than for morphine. Increased locomotion was observed after morphine, but not after endomorphin-1 or endomorphin-2. These findings extend previous results and suggest that endomorphins may have therapeutic potential for the treatment of acute pain.

Analgesics, Opioid↗

PubMed2000

Endogenous opiates: 1999.

This paper is the twenty-second installment of the annual review of research concerning the opiate system. It summarizes papers published during 1999 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunologic responses.

Animals↗

PubMed1999

Tyr-W-MIF-1-induced conditioned place preference.

Based on the evidence that Tyr-Pro-Trp-Gly NH2 (Tyr-W-MIF-1) produced dose-dependent, mu-opiate agonistic/antagonistic effects, we investigated whether Tyr-W-MIF- exhibited similar properties in the conditioned place preference (CPP) test. To examine the opiate agonistic effects on CPP, rats were conditioned with alternating ICV injections of saline and Tyr-W-MIF-1 (0 or 200 microg). This procedure resulted in Tyr-W-MIF-1-induced CPP. To examine the opiate antagonistic properties of low doses of Tyr-W-MIF-1, morphine-induced CPP was challenged with Tyr-W-MIF-1 (0, 25, 50, or 100 microg). Morphine-induced CPP was not affected by Tyr-W-MIF-1 at these doses. These findings show that in the CPP test Tyr-W-MIF-1 produced opiate agonistic effects at the high dose and was without opiate antagonistic properties at lower doses.

Animals↗

PubMed1999

Tolerance and morphine-induced cross-tolerance are not shown to Tyr-W-MIF-1 analgesia.

Tolerance and cross-tolerance between Tyr-W-MIF-1, a mixed micro-agonist/antagonist, and morphine were examined. Opiate dependence also was examined. Rats were pretreated with Tyr-W-MIF-1, morphine, or saline for 4 days. On day 5, the animals were tested for Tyr-W-MIF-1 analgesia, morphine analgesia, or naloxone-precipitated withdrawal. Tyr-W-MIF-1- and morphine-pretreated animals showed similar levels of dependence. Animals pretreated with Tyr-W-MIF-1 failed to express tolerance to Tyr-W-MIF-1 analgesia but did display cross-tolerance to morphine analgesia. Animals pretreated with morphine displayed tolerance to morphine analgesia but did not express cross-tolerance to Tyr-W-MIF-1 analgesia. Therefore, tolerance and morphine-induced cross-tolerance were not expressed to Tyr-W-MIF-1 analgesia.

Animals↗

PubMed1999

Endogenous opiates: 1998.

This paper is the twenty-first installment of our annual review of research concerning the opiate system. It summarizes papers published during 1998 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; eating and drinking; alcohol; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunologic responses; and other behaviors.

Alcohol Drinking↗

PubMed1998

Reduction of stress-induced analgesia following ethanol exposure in mice.

In the present study, we examined the effects of ethanol treatment on the subsequent expression of opioid and nonopioid forms of swim stress-induced analgesia (SSIA). In Experiment 1, mice were injected with ethanol (2.5 g/kg, i.p.) or an equal volume of saline once a day for two days. Animals received no treatment on day 3. On day 4, the animals were tested for opioid (3-min swim in water maintained at 32 degrees C) or nonopioid (3-min swim in water maintained at 20 degrees C) SSIA in the hotplate test (52 degrees C). Mice pretreated with ethanol injections showed a decrease in nonopioid SSIA, but not in opioid SSIA. In Experiment 2, mice were given an ethanol solution (10%) or tap water to drink for 15 days. On day 16, all animals were given tap water to drink. On day 17, the animals were tested for opioid or nonopioid SSIA. Neither form of SSIA was modified in mice that drank the ethanol solution. These results show that ethanol pretreatment can modify nonopioid endogenous analgesic responses in mice. Further, the route of administration influences the effects of ethanol pretreatment on SSIA.

Analgesia↗

PubMed1998

Tolerance to ethanol analgesia is not accompanied by cross-tolerance to morphine analgesia in rats.

In the present study, we examined the development of environment-independent and environment-dependent tolerance to ethanol-induced analgesia (EIA) and cross-tolerance with morphine-induced analgesia (MIA). To examine the development of environment-independent tolerance, male Long-Evans rats were given increasing amounts of ethanol (5 days each of 5% (v/v), 10% (v/v), and 15% (v/v)) added to their drinking water over a 15-day period. A control group was given plain tap water to drink. On day 16, all rats were given plain tap water to drink. On day 17, the animals were tested for EIA (2.5 g/kg, I.P.) or MIA (10 mg/kg, I.P.) in the hot plate test. To examine the development of environment-dependent tolerance, animals were injected with ethanol (2.5 g/kg, I.P.) or an equal volume of saline once a day for 2 days. On day 3, the animals received no treatment. On day 4, the animals were tested for either EIA (2.5 g/kg, I.P.) or MIA (10 mg/kg, I.P.) in the hot plate test. It was found that rats pretreated with ethanol (both self-administration and I.P. injections) displayed tolerance to EIA, which was not accompanied by cross-tolerance to MIA.

Analgesia↗

PubMed1998

Endogenous opiates: 1997.

This paper is the twentieth installment of our annual review of research concerning the opiate system. It summarizes papers published during 1997 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; eating and drinking; alcohol; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunologic responses; and other behaviors.

Animals↗

PubMed1997

A role of periaqueductal grey NMDA receptors in mediating formalin-induced pain in the rat.

In the present study we examined the role of periaqueductal grey (PAG) N-methyl-D-aspartate (NMDA) receptors in the perception of tonic and phasic pain. Under sodium pentobarbital anesthesia rats were implanted unilaterally with a guide cannula aimed at the PAG. Following a 7-14 day recovery period rats received an infusion of the NMDA antagonist, 2-amino-5-phosponopentanoic acid (AP5), or saline into the PAG. Five minutes after the infusion of AP5 rats were tested for analgesia in the formalin test, or in the hotplate test. AP5 injections into the PAG reduced pain in the formalin test, but not the hotplate test. These data show that NMDA receptors within the PAG are involved in the perception of tonic, inescapable pain as measured in the formalin test, but not phasic, escapable pain as measured in the hotplate test.

2-Amino-5-phosphonovalerate↗

PubMed1997

The role of corticosterone in the blockade of tolerance to morphine analgesia by formalin-induced pain in the rat.

We previously reported that morphine fails to produce analgesic tolerance when administered in the presence of formalin-induced pain, which may be related to activity of the hypothalamic-pituitary-adrenal axis. In the present study, we examined whether suppression of corticosterone secretion during pain prevents the blockade of tolerance to morphine analgesia. Male Long-Evans rats were injected with morphine (20 mg/kg) or saline for 4 consecutive days in the presence or absence of formalin-induced pain. To suppress corticosterone activity, some animals were injected daily with the corticosterone synthesis inhibitor, metyrapone (100 mg/kg), 24 h and 30 min before formalin injections. The analgesic effect of a test dose of morphine (10 mg/kg) was then measured in the tail-flick test 24 h after tolerance induction (i.e. day 5). The presence of pain during tolerance induction prevented the development of analgesic tolerance. Furthermore, inhibition of corticosterone synthesis by metyrapone prevented the blockade of tolerance by pain. These results suggest that the blockade of tolerance to morphine analgesia by formalin-induced pain depends on stress-induced corticosterone increases.

Animals↗

PubMed1997

Blockade of tolerance to stress-induced analgesia by MK-801 in mice.

The N-methyl-D-aspartate (NMDA) receptor has been implicated in mechanisms of tolerance to morphine-induced analgesia. The present study examined the role of the NMDA receptor in the development of tolerance to stress-induced analgesia (SIA). In the first experiment, mice were exposed to a stressor (a 3-min forced swim in water maintained at 32 degrees C) once daily for 15 consecutive days. Analgesia was measured 2 min after stress on the first and last day using the hot-plate test. To examine the role of the NMDA receptor in the development of tolerance to SIA mice were treated daily with the non-competitive NMDA receptor antagonist, MK-801, 15 min before swimming. Pretreatment with MK-801 was found to block both analgesia and tolerance. In a second experiment, to examine whether SIA and tolerance to SIA are mediated by similar or different mechanisms, mice were injected daily with MK-801 after analgesia had dissipated (1 h following swim). Tolerance to SIA was blocked by delayed injections of MK-801. These results suggest that the NMDA receptor is involved in mechanisms of tolerance to SIA, independent of its role in analgesia.

Analgesia↗

PubMed1996

Reduction of autotomy following peripheral neurectomy by a single injection of bupivacaine into the cingulum bundle of rats.

Peripheral neurectomy in rats is followed by autotomy of the denervated zone, which is assumed to represent an index of pain or dysesthesia. In the present study, we examined whether a single injection of a local anesthetic (bupivacaine) into the cingulum bundle at the time of nerve section could reduce autotomy. It was found that a temporary anesthetic blockade of the cingulum at the time of nerve section delayed the onset and reduced the overall degree of autotomy. However, injections given shortly after nerve section had no significant effects. These results demonstrate that temporary blockade of cingulum activity at the time of nerve section reduces autotomy for periods that exceed the duration of the anesthetic block.

Animals↗

PubMed1994

Descending modulation of central neural plasticity in the formalin pain test.

Subcutaneous injection of formalin produces a biphasic profile of pain response: a transient early phase followed by a tonic late phase. A number of studies have indicated that the development of the late phase of formalin pain is dependent upon prolonged changes in central neural function produced by neural activity that is generated during the early phase (i.e. central sensitization). In support of this, the present demonstrates that stimulation- or morphine-produced analgesia derived from the periaqueductal grey (PAG) during the early phase prevents the development of the phase. These results suggest that descending mechanisms of pain inhibition, as reflected by PAG stimulation- and morphine-produced analgesia, can prevent the development of central neural plasticity following injury.

Analgesia↗

PubMed1993

Morphine fails to produce tolerance when administered in the presence of formalin pain in rats.

The present study examined the development of tolerance to morphine analgesia under conditions in which morphine was administered in the presence or absence of pain induced by subcutaneous injection of 50 microliters of 2.5% formalin into the hind paw of rats. Animals were injected with morphine (25 mg/kg, i.p.) or saline for 3 consecutive days either in the presence of pain (10 min after formalin injection) or in the absence of pain (6 h prior to formalin injection). On the 4th day, tolerance to the analgesic effect of test doses of morphine (6 or 10 mg/kg) was assessed in the formalin and tail-flick tests, respectively. Significant tolerance in both tests was observed in animals receiving morphine in the absence of pain during the tolerance induction period, but not in animals receiving morphine in the presence of pain.

Animals↗

PubMed1993

Formalin-induced pain antagonizes the development of opiate dependence in the rat.

Clinical studies have suggested that patients who take morphine for pain relief do not show a high degree of dependence. The present study examined the development of naloxone-precipitated withdrawal in rats receiving morphine in the presence or absence of formalin-induced pain. Morphine (10 mg/kg, i.p.) or saline was administered for 4 consecutive days 10 min after a subcutaneous injection of 50 microliters of 2.5% formalin or saline into the hind-paw. On the 5th day, rats were injected with naloxone (1 mg/kg, i.p.) and observed for signs of precipitated withdrawal (ptosis, teeth chattering and excretion/diarrhea). Naloxone-precipitated withdrawal symptoms were significantly greater in rats that received morphine in the absence of pain than in rats that received morphine in the presence of pain.

Animals↗

PubMed1993

NMDA receptor antagonists, MK-801 and ACEA-1011, prevent the development of tonic pain following subcutaneous formalin.

Subcutaneous injection of formalin produces a biphasic pain response: an early, transient phase followed by a late tonic phase. The present study examined the involvement of the N-methyl-D-aspartic acid (NMDA) receptor in the development of the late pain produced following subcutaneous injection of formalin into the hind paw in mice. Blockade of the NMDA receptor by its non-competitive antagonist, MK-801, prior to formalin injection, but not after, reduced pain during the late phase. Similarly, blockade of the NMDA receptor allosteric site by the novel glycine site antagonist, ACEA-1011, also reduced the pain response in the late phase. These results suggest that the development of the late phase of formalin pain is due to NMDA-mediated activity during the early phase.

Analgesics↗