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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In barbiturate anaesthetized cats, tonic inhibition of the excitation of lumbar dorsal horn neurones by impulses in unmyelinated primary afferents was measured by reversibly cooling the spinal cord at the thoraco-lumbar junction. Tonic inhibition was reduced by microinjection of the GABA analogue, piperidine-4-sulphonic acid (2.5 nM in 0.5 microliter) mainly at AP -7, L 2-5 and V -8 to -10. This area in the ventrolateral medulla is just ventral to the facial nucleus and has been shown to be important in cardiovascular control, particularly in relation to fear-defence reactions. It is proposed that tonic inhibition of the nociceptive responses of spinal neurones is part of such a reaction in response to the trauma of surgery. Since previous experiments had shown that the ventrolateral medulla was important in spinal inhibition produced by PAG stimulation, these experiments support the proposal that analgesia does not occur in isolation but is part of a complex behavioural response of an animal in a potentially injurious environment.
Pain 1986 Dec
PMID:Brain-stem areas tonically inhibiting dorsal horn neurones: studies with microinjection of the GABA analogue piperidine-4-sulphonic acid. 380 42

Cocaine hydrochloride (50 mg) pellets implanted subcutaneously in male Wistar rats potentiated the analgesia of morphine, levorphanol, methadone and buprenorphine as measured by the tail-withdrawal test. Potentiated opiate analgesia was abolished by naloxone and further enhanced by desipramine and phenoxybenzamine. Yohimbine, alpha-methyl p-tyrosine, haloperidol, zimelidine, methysergide, p-chlorophenylalanine produced no significant effect on potentiated opiate analgesia. Pseudo-cocaine (dextro-cocaine), which is several-fold less potent than cocaine as an inhibitor of noradrenaline and dopamine reuptake in the CNS, had no significant effect on opiate analgesia. Analgesia produced by low doses of baclofen, a GABA agonist, was also not potentiated by cocaine. This study suggests a predominant role for noradrenaline in the stereospecific potentiation of opiate analgesia by cocaine.
Pain 1987 Jan
PMID:Stereospecific potentiation of opiate analgesia by cocaine: predominant role of noradrenaline. 382 92

A newly developed synaptosomal model was used to evaluate the in vivo effects of the GABA-elevating drugs aminooxyacetic acid (AOAA, 30 mg/kg i.p.) and valproic acid (VPA, 200 mg/kg i.p.) on GABA levels in nerve endings of 11 brain regions in rats as a function of time after administration. The data obtained were compared with the magnitude and time course of the effects of both drugs in rats on body temperature, pain response and against seizures induced by electroshock, pentylenetetrazol and 3-mercaptopropionic acid. Following AOAA, maximum increases in synaptosomal GABA levels of brain regions were observed 6 hr after administration. At this time, GABA was significantly elevated up to 300% over control values in synaptosomal fractions from all 11 regions. However, the hypothermic and antinociceptive effects of the drug as well as its anticonvulsant action against electroshock and pentylenetetrazol induced seizures were maximal 1 hr after injection and had vanished after 6 hr, i.e. at the time of maximum GABA increases in synaptosomes. The only pharmacological effect of AOAA which paralleled the time course of the synaptosomal GABA elevation was the attenuation of seizures induced by 3-mercaptopropionic acid. Following VPA, the effect on synaptosomal GABA levels was much more rapid in onset and significant increases were already determined 5 to 30 min after administration. Significant increases of up to 80% over control values were found in synaptosomal fractions from olfactory bulb, frontal cortex, hippocampus, hypothalamus, tectum, substantia nigra and cerebellum. In contrast to AOAA, the time course of the synaptosomal GABA increases, at least in some regions, was similar to the time course of VPA's antinociceptice effects and its anticonvulsant effects in the three seizure models studied. The data may suggest that AOAA and VPA increase different pools of GABA within nerve terminals, only one of which is involved in GABA-mediated neurotransmission.
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PMID:In vivo effects of aminooxyacetic acid and valproic acid on nerve terminal (synaptosomal) GABA levels in discrete brain areas of the rat. Correlation to pharmacological activities. 392 47

Previous studies have demonstrated the GABAergic system in the hippocampus to be a major controlling factor in the reversal of learned helplessness by antidepressants. In the present work, animals in which learned helplessness (LeH) was induced by exposure to uncontrollable electric shock demonstrated a decreased depolarization-induced release of GABA relative to controls, and an increased release of hippocampal glutamate. Injection of bicuculline but not glutamate into the hippocampus produced a behavioral state identical to that induced by uncontrollable shock, but had no influence on pain sensitivity. When flux through the "small" hippocampal pool of GABA was determined, chronic treatment with imipramine or iprindole, but lorazepam or chlorpromazine elevated this measure. These three findings along with those of prior experiments, suggest a controlling role for GABA in the learned helplessness model of depression.
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PMID:GABAergic modulation of learned helplessness. 611 82

The effects of benzodiazepine (mainly diazepam) on the following central action of narcotic analgesics were tested: antinociceptive action (Randall-Selitto and hot plate tests), hypermotility, inhibition of methylphenidate stereotypy, catalepsy. Diazepam, in doses not affecting the pain threshold markedly potentiated morphine, codeine, etorphine, pentazocine and fentanyl antinociception. Hypermotility produced by morphine and fentanyl was inhibited by pretreatment with chlordiazepoxide, diazepam and clonazepam. Diazepam potentiated the inhibitory effect of opiates on methylphenidate-induced stereotyped gnawing in mice and increased the catalepsy induced by morphine and fentanyl in rats. In all experiments the effects of diazepam were suppressed by the substances which impair GABA-ergic neurotransmission: bicuculline and picrotoxin. Obtained results indicate that benzodiazepine potentiate the antinociceptive and cataleptogenic effects of opiates and their inhibitory influence on methylphenidate stereotypy. However, these drugs antagonize locomotor hyperactivity in mice. All these actions seem to be related to facilitation of GABA-ergic neurotransmission by benzodiazepines.
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PMID:Effect of benzodiazepines on the central action of narcotic analgesics. 613 69

The effect of the intrathecal administration of midazolam 0.5-1.0 mg in 1-2 ml of physiological saline solution, has been observed on responses evoked in renal sympathetic nerves by supramaximal electrical stimulation of radial and tibial nerves. In artificially ventilated dogs anaesthetized with alpha-chloralose, the intrathecal administration of midazolam caused a marked depression of reflexes evoked from the tibial nerve but had no effect on either spontaneous sympathetic activity or reflexes evoked by radial nerve stimulation. Neither the small amount (1-2 microliters) of benzyl alcohol, present as a preservative (administered intrathecally), nor midazolam 1 mg kg-1 i.v. caused any significant depression of the evoked somato--sympathetic reflexes. The effects of intrathecal midazolam were reversed by the benzodiazepine antagonists Ro 15-1788 1 mg kg-1 i.v. and Ro 15-3505 1-2 mg kg-1 i.v. but not by naloxone 2 mg i.v. It is suggested that the antinociceptive effect of locally applied midazolam could be the result of a non-opioid GABA-mediated system which may have implications in the management of pain.
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PMID:Depression of nociceptive sympathetic reflexes by the intrathecal administration of midazolam. 613 38

The influence of naloxone (a narcotic antagonist), bicuculline (a GABA antagonist), phentolamine (an alpha-blocking agent), propranolol (a beta-adrenergic blocking agent), haloperidol (a dopaminergic blocking agent), methysergide (a serotonergic blocking agent) and atropine (a muscarinic blocking agent), on the antinociceptive effects induced by carbamazepine, baclofen, pentazocine and morphine, were investigated with a new antinociception test, using the trigeminal pain induced by application of bradykinin onto the tooth pulp of the rat. The antinociceptive effect of carbamazepine was significantly inhibited by bicuculline, phentolamine, propranolol and haloperidol but not by naloxone, methysergide and atropine. The effect of baclofen was significantly reduced by naloxone, bicuculline, propranolol and atropine but not by phentolamine, haloperidol and methysergide. The antinociceptive actions of pentazocine and morphine on trigeminal pain were significantly reduced by naloxone and phentolamine, and by naloxone alone, respectively. These results suggest the involvement of different neurotransmitters in the antinociceptive effects of the four analgesic drugs on trigeminal pain induced by bradykinin.
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PMID:Neurotransmitter-blocking agents influence antinociceptive effects of carbamazepine, baclofen, pentazocine and morphine on bradykinin-induced trigeminal pain. 614 40

Physiological events involved in nociception and pain perception are examined. Substance P could be a primary afferent transmitter of certain nociceptive information. Transmission of this information can be modulated within the spinal cord by intrinsic and descending mechanisms. The intrinsic mechanism involves inhibitory opiate effects within substantia gelatinosa. Centres for descending systems are located in medulla and periaqueductal gray matter. They are activated by exogenous narcotic agonists, and by regional connections. Descending inhibitory pathways are serotonergic and noradrenergic. GABA and glycine are also possibly involved in antinociception. Narcotics have been shown to produce analgesia when administered to the intrathecal or epidural spaces of humans. These routes are still experimental. The place of clinical modification of transmitter system is discussed, but no conclusions or recommendations can be made at this early stage.
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PMID:Pharmacology of pain and analgesia. 615 88

Substance P is present in numerous organs (salivary glands, trachea, pancreas, kidneys, bladder and prostate) and in various parts of the central and peripheral nervous system, notably substantia nigra, hypothalamus, pineal body and dorsal horn of the spinal cord. It is a potent stimulant of salivary secretion and intestinal motility, a vasodilator in muscles and fatty tissues and an inhibitor of insulin release. Its main role, however, lies in the transmission of pain, where it seems to act as neuromodulator. Released when nociceptive fibers are activated at the same time as the fast-acting neuromediator, it enhances and prolongs the effects of the latter. Opiates inhibit its release. In addition, substance P is present in the excitatory neurones of the corpus striatum-substantia nigra pathway, which also has GABA-containing inhibitory neurones, and this pathway is known to modulate the dopaminergic nigra-striatum pathway. The global function of substance P, therefore, seems to keep the central nervous system in a state of alert through activation of the cerebral cortex and assistance in the transmission of pain.
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PMID:[Substance P]. 616 77

The spinal nociceptive system is the target of various pain depressing agents. It is capable to function without control from the brain. It is activated by tissue damage which, by excitation of nociceptive afferents, evokes activity in axons ascending to the brain (sensory nociceptive response) and in spinal reflex pathways (motor and autonomic responses). The prototype of an analgesic agent, morphine, suppresses nociceptive responses by binding to opiate receptors; it imitates the effect of the transmitter(s) released from endorphinergic neurones. Pentobarbital and diazepam reduce nociceptive (and non-nociceptive) responses by acting on the GABA receptor complex; both drugs facilitate the effect of the transmitter GABA which mediates presynaptic inhibition in the spinal cord. Pentobarbital may produce its effects by an additional action on postsynaptic neurone membranes. Clonidine depresses nociceptive responses, probably by imitating the action of the inhibitory transmitter, noradrenaline. Substance P acts as a "synaptic modulator"; it may facilitate or inhibit nociceptive responses. Ceruletide and cholecystokinin octapeptide depress nociceptive motor responses but do not affect the nociceptive sensory response. This indicates that motor and sensory responses of the spinal nociceptive system are not rigidly linked together. With the help of appropriate drugs, it is possible to manipulate them separately.
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PMID:Pain-depressing agents and the spinal nociceptive system. 620 17


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