nociceptive tests, such as the tail-flick or hot-plate test (Jensen 1986; Tung and 
Yaksh 1982), and intracerebral injection of morphine inhibits the firing of dorsal 
horn neurons that respond selectively to noxious stimuli (Bennett and Mayer 
1979; Du et al. 1984; Gebhart et al. 1989). Furthermore, the antinociceptive 
effects of systemic or intracerebral injection of morphine are attenuated by 
lesions of the brain stem or spinal cord (Barton et al. 1980; Basbaum et al. 
1976, 1977) and can be antagonized by IT injection of monoamine antagonists 
(Proudfit and Hammond 1981; Jensen 1986). However, there is contradictory 
neurophysiological evidence that indicates that intracerebral and ICV morphine 
decreases, rather than increases, descending controls to produce analgesia 
(Bouhassira et al. 1988; Dickenson and Le Bars 1987; Duggan et al. 1980). 
The authors’ results provide strong evidence in support of the hypothesis that 
both ICV morphine and DAMGO produce analgesia and suppression of spina! 
cord Fos immunoreactivity by increasing descending controls. 
To specifically test this hypothesis, Gogas and colleagues (1991) studied 
the effects of the administration of supraspinal opioids in animals that 
underwent bilateral lesions of the spinal cord pathway through which 
opioids exert their effect (see the dorsolateral funiculus [DLF]). They predicted 
that DLF lesions would totally block the opioid-mediated behavioral analgesia 
and the suppression of spinal cord Fos immunoreactivity. In fact, the dose 
of ICV DAMGO that produced 100-percent behavioral analgesia in normal 
animals (0.60 \ig) had no effect on either behavior or Fos immunoreactivity in 
animals with DLF lesions (figure 11). This finding supports the conclusion that 
supraspinal opioids produce their analgesic effects by increasing, rather than 
decreasing, the activity of descending control systems. This experiment again 
illustrates the advantage of monitoring large populations of neurons with Fos 
immunocytochemistry to answer questions that previously could be addressed 
only at the single-cell level. 
CONCLUSION 
The examples discussed in this report demonstrate the usefulness and validity 
of monitoring Fos expression to assess the activity of populations of CNS 
neurons. However, several important caveats need to be underlined when 
interpreting the results of these experiments. First, there is no unequivocal 
way of knowing whether a Fos-expressing neuron is, in fact, nociresponsive. 
This assumption is based on electrophysiological characterization of neurons 
in the different spinal cord laminae. Similarly, if a neuron does not express 
the Fos protein, one cannot conclude that the unlabeled neuron is not 
nociceptive. Also, since the function of the Fos protein in spinal cord neurons 
is not presently known, no conclusions can be drawn regarding the biological 
significance of a neuron expressing Fos immunoreactivity. In spite of these 
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