Biomedical subjects

Steven F Maier

Publications and source records attributed to Steven F Maier.

77 records · Page 5Linked to original sources

PubMed1994

Acute and conditioned hyperalgesic responses to illness.

It has been argued that pain functions to facilitate recovery from injury and/or illness by stimulating recuperative behaviors. If this is the case, then hyperalgesia might be expected to be part of the constellation of adaptations that occur during sickness. The present series of studies tested two agents that induce illness (lithium chloride and bacterial cell-wall endotoxin (lipopolysaccharide)) to determine their acute effects on pain responsivity in rats. Both agents produced hyperalgesia as measured by the tail-flick and formalin tests. This enhanced responsivity appears to be specific to pain since (a) no enhanced response was observed to a non-painful stimulus (6 g von Frey hairs), and (b) the effect could not be accounted for by changes in tail skin temperature. In addition, a conditioned taste aversion paradigm was used to examine the possibility that illness-induced hyperalgesia could be conditioned to a novel taste (saccharine). This procedure was successful in producing a conditioned hyperalgesia which was comparable in magnitude and duration to acute illness induced pain facilitation. Taken together, this series of studies suggests that such pain facilitation might have adaptive functions similar to those ascribed to other illness-induced behaviors.

Animals↗

PubMed1982

Controllability, coping behavior, and stress-induced analgesia in the rat.

Exposure to painful or stressful stimuli produces an analgesic reaction which can persist for 1-2 h post-stress. In the typical stress-induced analgesia study the subject is not permitted to alter or exert control over the aversive event to which it is exposed. That is, its behavior affects neither the duration or intensity of the event. The experiments reported here attempted to determine whether this inability of the subject to control the aversive event is an important determinant of stress-induced analgesia, or whether simple exposure to painful events is a sufficient condition for its production. In the first experiment rats were given either escapable electric shocks (the subject's behavior could terminate the shock), equal amounts of inescapable shock, or no shock. Tail-flick to radiant heat was assessed 30 min later. The group given inescapable shock was strongly analgesic, while the group given an equal amount of escapable shock was only mildly analgesic. Thus the controllability of the shock or the availability of a coping response determined the antinociceptive reaction which followed. The second experiment revealed that this differential effect of controllability on tail-flick responding is masked, shortly after the end of the shock session, by a transient analgesic effect of shock which is not sensitive to the controllability dimension. The implications of these results for stress-induced analgesia and the activation of opioid systems are discussed.

Adaptation, Psychological↗

PubMedDate not supplied

Glial activation and pathological pain.

Pain is a sensation we have all experienced. For most of us, the pain has been temporary. However, for patients with pathological pain, the pain experience is unending, with little hope for therapeutic relief. Pathological pain is characterized by an amplified response to normally innocuous stimuli, and an amplified response to acute pain. Pathological pain has long been described as the result of dysfunctional neuronal activity. While neuronal functioning is indeed altered, there is significant evidence showing that exaggerated pain is regulated by the activation of astrocytes and microglia. In exaggerated pain, astrocytes, and microglia are activated by neuronal signals including substance P, glutamate, and fractalkine. Activation of glia by these substances leads to the release of mediators that then act on other glia and neurons. These include a family of proteins called "proinflammatory cytokines" released from microglia and astrocytes. These cytokines have been shown to be critical mediators of exaggerated pain. Some patients with pathological pain also report "extra-territorial" and/or "mirror" image pain. That is, exaggerated pain is experienced not only in the area of trauma. In extra-territorial pain, pain is also perceived as arising from neighboring healthy tissues outside of the site of trauma. In the rare cases of mirror-image pain, such pain is perceived as arising from the healthy, corresponding body part on the opposite side of the body. New data suggest that activation of astrocyte communication via gap junctions may mediate such spread of pain. While traditional therapies for pathological pain have focused on neuronal targets, the following review describes glia as newly recognized mediators of exaggerated pain, and as new therapeutic targets. Moreover, the glial-neuronal interactions discussed here are likely not exclusive to pain, but rather are likely to play significant roles in other behavioral phenomena.

Animals↗

PubMedDate not supplied

Modulation of the locomotor properties of morphine and amphetamine by uncontrollable stress.

We have recently demonstrated that exposure to a single session of inescapable shock (IS), but not to identical amounts and distributions of escapable shock (ES), increases the rewarding properties of morphine, as measured by conditioned place preference (CPP). Interestingly, we also found that exposure to IS has no effect, or even interferes with amphetamine CPP. The present study explored whether the potentiating effect of IS on morphine reward, but not amphetamine reward, would generalize to the locomotor properties of these drugs. The locomotor response to morphine and amphetamine was measured 120 h following exposure to either IS or home cage control (HCC) treatment. On test day, the activity of all subjects was measured for 1 h before and 3 h after drug administration. The results demonstrated that exposure to IS potentiated the locomotor response to morphine, while having no effect on the response to amphetamine. An additional study investigated whether the effects of IS on the locomotor properties of morphine were sensitive to stressor controllability, by comparing the influence of IS, ES, or control treatment. Again, IS potentiated the locomotor properties of morphine, while exposure to ES and control treatment had no effect.

Amphetamine↗

PubMedDate not supplied

"Brain-specific" nutrients: a memory cure?

OBJECTIVE: We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E). RESULTS: In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. CONCLUSIONS: In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.

Acetylcarnitine↗