Are opioid-sensitive neurons in the rostral ventromedial medulla inhibitory interneurons?

mu-Opioid agonists frequently activate output neurons in the brain via disinhibition, that is, by inhibiting "secondary cells," which results in disinhibition of "primary cells," considered to be output neurons. Secondary cells are generally presumed to be inhibitory interneurons that serve only to regulate the activity of the output neurons. However, studies of the opioid-sensitive neurons in the rostral ventromedial medulla, a region with a well-documented role in nociceptive modulation, indicate that the opioid-inhibited neurons in this region (termed "on-cells" when recorded in vivo) have a distinct functional role that parallels and opposes the output of the subset of RVM neurons that are activated following opioid administration, the "off-cells." The aim of the present study was to analyze the relative timing of on- and off-cell reflex-related firing in the rostral ventromedial medulla to help determine whether on-cells are likely to function as inhibitory interneurons in this region. On- and off-cells display complementary firing patterns during noxious-evoked withdrawal: off-cells stop firing and on-cells show a burst of activity. If on-cells are inhibitory interneurons mediating the off-cell pause, the on-cells would be expected to begin their reflex-related discharge before the off-cells cease firing. To examine this we recorded activity of on- and off-cell pairs during heat-evoked paw or tail withdrawal in lightly anesthetized rats. For each cell pair, we measured the onsets of the off-cell pause and the on-cell burst. Contrary to what would be expected if on-cells were inhibitory interneurons, off-cells typically ceased firing before on-cells began reflex-related firing, with a mean 481 (+/-69) ms lag between the final off-cell spike and the first on-cell spike. This suggests that on-cells do not mediate the off-cell pause, and points instead to presynaptic mechanisms in opioid-mediated disinhibition of medullary output neurons. These data also support an independent role for on-cells in pain modulation.

Prostaglandin E2 in the medial preoptic area produces hyperalgesia and activates pain-modulating circuitry in the rostral ventromedial medulla.

Prostaglandin E2 (PGE2) produced in the medial preoptic region (MPO) in response to immune signals is generally accepted to play a major role in triggering the illness response, a complex of physiological and behavioral changes induced by infection or injury. Hyperalgesia is now thought to be an important component of the illness response, yet the specific mechanisms through which the MPO acts to facilitate nociception have not been established. However, the MPO does project to the rostral ventromedial medulla (RVM), a region with a well-documented role in pain modulation, both directly and indirectly via the periaqueductal gray. To test whether PGE2 in the MPO produces thermal hyperalgesia by recruiting nociceptive modulating neurons in the RVM, we recorded the effects of focal application of PGE2 in the MPO on paw withdrawal latency and activity of identified nociceptive modulating neurons in the RVM of lightly anesthetized rats. Microinjection of a sub-pyrogenic dose of PGE2 (50 fg in 200 nl) into the MPO produced thermal hyperalgesia, as measured by a significant decrease in paw withdrawal latency. In animals displaying behavioral hyperalgesia, the PGE2 microinjection activated on-cells, RVM neurons thought to facilitate nociception, and suppressed the firing of off-cells, RVM neurons believed to have an inhibitory effect on nociception. A large body of evidence has implicated prostaglandins in the MPO in generation of the illness response, especially fever. The present study indicates that the MPO also contributes to the hyperalgesic component of the illness response, most likely by recruiting the nociceptive modulating circuitry of the RVM.

Multilevel performance probability: a meta-analytic integration of expectancy and self-efficacy.

A meta-analysis of one approach to measuring expectancy and self-efficacy was conducted. Although used for over 25 years, this measure has yet to be named or integrated across the two theoretical domains. We proposed to label this measure a Multilevel Performance Probability and conducted a meta-analysis. The search for empirical tests of expectancy and self-efficacy using this procedure yielded 16 studies with ratings which could be subjected to meta-analysis. Five studies with 8 tests were taken from expectancy studies and 11 studies with 47 tests from studies of self-efficacy. In total, the analyses involved 7,444 subjects across 55 tests of the Multilevel Performance Probability to performance relationship. Examination of the measure as a predictor of performance gave a mean r of .51 (p<.001) which is in the same direction and larger than values from other meta-analyses conducted within each of the two theoretical domains (rs of .21 and .38).