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Biomedical subjects

H Akil

Publications and source records attributed to H Akil.

At least 289 records · Page 16Linked to original sources
PubMed1977

Pain reduction by electrical brain stimulation in man. Part 1: Acute administration in periaqueductal and periventricular sites.

Acute studies performed in five patients indicate that electrical stimulation of the brain could be a powerful tool for the reduction or control of intractable pain. While chronic or spontaneous pain could be relieved by stimulation of the periaqueductal gray matter, the accompanying side effects render it impossible to stimulate this site regularly. On the other hand, stimulation of medial thalamic sites, particularly medial to the nucleus parafascicularis, yielded good relief of chronic pain at parameters which did not cause many undesirable side effects. The same parameters also produced inhibition of acute pain in two of the five patients.

Aged↗
PubMed1977

Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter.

Electrical stimulation of the periventricular gray matter is an effective means of relieving several types of pain without destruction of neural tissue. The effects are long lasting, often bilateral, and with judicious use do not appear subject to adaptation. However, sustained uninterrupted stimulation for several hours does lead to a reversible decrease in effectiveness. Side effects from stimulation are minimal and cause little or no untoward emotional changes. The results are discussed in terms of activation of an endogenous pain inhibitory mechanism that involves naturally occurring opiate-like factors such as the enkephalins and endorphins.

Adult↗
PubMed1976

Antagonism of stimulation-produced analgesia by naloxone, a narcotic antagonist.

Analgesia produced by focal electrical stimulation of the brain is partially reversed by the narcotic antagonist naloxone. The absence of complete reversal does not appear to be caused by inadequate doses of naloxone since doses higher than 1 milligram per kilogram of body weight did not increase the antagonism. It is suggested that stimulation-produced analgesia may result, at least in part, from release of an endogenous, narcotic-like substance, such as that recently reported by other investigators.

Analgesia↗
PubMed1975

Monoaminergic mechanisms of stimulation-produced analgesia.

The roles played by the cerebral monoamines (dopamine, noradrenaline and serotonin) in stimulation-produced analgesia (SPA) have been investigated in the rat employing the tail flick test. SPA was elicited through bipolar electrodes chronically implanted in the mesencephalic periaqeductal gray matter, an area previously shown to yield potent and reliable analgesic effects. Four approaches were used to alter transmission in monoamine pathways. (1) Depletion of monoamines by administration of tetrabenazine (TBZ), p-chlorophenylalanine (PCPA), alpha-methyl-para-tyrosine (AMPT), or disulfiram. (2) Replacement of depleted monoamine stores by appropiate precursors (5-HTP or L-DOPA) in combination with a peripheral decarboxylase inhibitor. (3) Potentiation of monoamine systems by administration of precursors to previously untreated animals or by administration of a dopamine receptor stimulator, apomorphine. (4) Blockade of catecholamine receptors by haloperidol or of dopamine receptors by pimozide. These four approaches yielded internally consistent results. Depletion of all 3 monoamines (TBZ) led to a powerful inhibition of SPA. Original levels of SPA were restored by injection of either 5-HTP or L-DOPA. Specific depletion of serotonin (PCPA) caused a reduction in SPA, whereas elevation of serotonin levels (5-HTP) caused an increase in SPA. Dopamine receptor blockade (pimozide) decreased SPA, whereas the precursor (L-DOPA) and a dopamine receptor stimulator (apomorphine) increased SPA. On the other hand, selective depletion of noradrenaline (disulfiram) caused an increase in SPA; and at a time when noradrenaline levels are depressed and dopamine levels are elevated (AMPT + L-DOPA), SPA was seen to be particularly enhanced. thus, dopamine and serotonin appear to facilitate SPA, whereas noradrenaline appears to inhibit it. When a general catecholamine receptor blocker (haloperidol) was employed, SPA was diminished, suggesting that the influence of dopamine in SPA is greater than that of noradrenaline. Most of the drugs used in this study significantly altered SPA at doses which left baseline tail flick latency unaffected. It would appear, therefore, that SPA has a neural substrate at least partly independent of that underlying baseline pain responsiveness. Consideration is given to various ascending and descending monoamine system as possible component paths in this neural substrate of SPA. Finally, the present results are discussed in relation to studies by others on the site and mechanism of morphine's analgesic action. Some striking parallels between SPA and morphine analgesia are noted. These suggest the existence of a common pain-inhibitory system in the brain activated by morphine and by focal electrical stimulation.

5-Hydroxytryptophan↗
PubMed1971

Analgesia from electrical stimulation in the brainstem of the rat.

Stimulation at several mesencephalic and diencephalic sites abolished responsiveness to intense pain in rats while leaving responsiveness to other sensory modes relatively unaffected. The peripheral field of analgesia was usually restricted to one-half or to one quadrant of the body, and painful stimuli applied outside this field elicited a normal reaction. Analgesia outlasted stimulation by up to 5 minutes. Most electrode placements that produced analgesia also supported self-stimulation. One placement supported self-stimulation only in the presence of pain.

Aggression↗
PubMedDate not supplied

Pulse-chase studies of the POMC/beta-endorphin system in the pituitary of acutely and chronically stressed rats.

Experiments were carried out to determine whether stress induces biochemical changes in the pro-opiomelanocortin (POMC) system in anterior (AL) and intermediate-posterior lobe (IPL) of rat. In a series of pulse-chase experiments, acute stress led to an increase in POMC biosynthesis and shorter half-life in AL. However, when the animals were chronically stressed, the AL no longer exhibited increased POMC synthesis. On the other hand, in the IPL, acute stress did not produce any biochemical changes, but chronic stress led to an increase in POMC synthesis and shorter half-life. These data suggest that AL and IPL are affected by acute and/or chronic exposure to stress in opposite directions and that the POMC system in AL may play an important role in stress-induced analgesia.

Acute Disease↗
PubMedDate not supplied

The signal peptide of pro-opiomelancortin: validation of a specific radioimmunoassay.

The N-terminus portion of the POMC leader sequence (signal peptide) was synthesized, and an antiserum was raised against it. A radioimmunoassay was developed which is effective at a dilution of 1:500,000, and sensitive at less than 1 fmole/tube. Since leader sequences often exhibit structural homologies, and since synthetic peptides are not readily available, we resorted to an unusual procedure to establish specificity. This involved extraction of pituitary RNA, cell-free translation to produce the pre-prohormones, and purification by B-END and signal antibody affinity columns. The eluates were then tested by SDS gel electrophoresis and by multiple immunoprecipitations. All results showed that the signal antibody captured a single molecular species, approximately 30,000 in MW, which was also captured by the B-END column, and was immunoprecipitable by B-END and ACTH antisera. It therefore appears that this antibody selectively measures the POMC leader sequence and should be valuable in measuring the newly synthesized pre-prohormone.

Amino Acid Sequence↗
PubMedDate not supplied

Dynorphin is located throughout the CNS and is often co-localized with alpha-neo-endorphin.

The opioid peptide dynorphin has been described as widely distributed in CNS when measured by RIA. Our previous immunohistochemical studies have only demonstrated dynorphin cells as those containing AVP. We now report the specific localization of dynorphin throughout the neuraxis. Further, dynorphin and alpha-neo-endorphin have been co-localized to the same magnocellular neurosecretory cells in hypothalamus. We report agreement with the findings of others and extend them to include a cell group in dorsomedial hypothalamus, further strengthening the association between dynorphin and alpha-neo-endorphin.

Animals↗
PubMedDate not supplied

Plasma beta-endorphin-like immunoreactivity, self reported pain perception and anxiety levels in women during pregnancy and labor.

Plasma Beta-endorphin (B-END) immunoreactivity was measured in 19 men, 16 women at midcycle, and ten pregnant women at various points in their pregnancies. There is a significant difference between the levels measured in males and females (t = 3.74, df = 31, p = .0007). Pregnant women demonstrated a steady increase in plasma Beta-End-like immunoreactivity between second and third trimester and through labor. The levels dropped rapidly postpartum. The material being measured is predominantly B-end-sized. Psychological studies indicate that these changes are not strongly correlated with pain perception or self-reported anxiety levels.

Adult↗
PubMedDate not supplied

Peptide F (pro-enkephalin fragment): radioimmunoassay, and stress-induced changes in adrenal.

Utilizing a nine amino-acid (Asp-Glu-Leu-Tyr-Pro-Leu-Glu-Val-Glu) non-enkephalin containing fragment of Peptide F from the pro-enkephalin molecule, a radioimmunoassay was developed. Extraction of bovine, rat, and guinea pig adrenomedullary preparations demonstrated this fragment to be present and apparently partially conserved across species. In rats, acute inescapable foot-shock stress led to a significant decrease of the immunoreactive material in the adrenal medulla. Chronic daily stress for two weeks resulted in an inability of the adrenals to alter F levels upon subsequent stress. The existence of F-like immunoreactivity and its alteration by environmental manipulation, suggest that it may play a unique physiological role.

Adrenal Medulla↗
PubMedDate not supplied

Increase in delta, but not mu, receptors in MSG-treated rats.

Neonatal treatment of rats with Monosodium Glutamate (MSG) has been demonstrated to destroy cell bodies of neurons in the arcuate nucleus including the brain beta-endorphin (B-END) system. The effects on opiate receptors of the loss of B-END is unknown. Seven to nine month old rats treated with MSG on the first two postnatal days and litter matched untreated control rats were decapitated and their brains dissected into several regions. Opiate receptor assays were carried out with [3H] morphine (mu receptor ligand) and [3H] DADL (delta receptor ligand) for each brain region for both MSG-treated and control rats simultaneously. Scatchard plot analyses showed a selective increase in delta receptors in the thalamus only. No corresponding change in mu receptors in the thalamus was found. The cross-competition IC50 data supported this conclusion, showing a loss in the potency of morphine in displacing [3H] DADL in the thalamus of MSG treated rats.

Animals↗