Mechanisms of Opioid-Mediated 
Antinociception: Correlation of Fos 
Expression and Behavior 
Kathleen R. Gogas, Jon D . Levine , and Allan /. Basbaum 
INTRODUCTION 
Recent studies have emphasized the utility of monitoring the expression of 
immediate early genes (lEGs) to map functionally relevant pathways in the 
central nervous system (CNS) (Hunt et al. 1987; Morgan et al. 1987; Sager 
et al. 1 988). The authors’ laboratory has been studying the expression of the 
c -fos gene to characterize the circuitry underlying the transmission of noxious 
(i.e., painful) information into the spinal cord (Menetrey et al. 1989; Presley 
etal. 1990; Gogas et al. 1991). Despite the rapid growth of this new field, 
many questions are still unsettled as to the appropriateness of c -fos message 
or Fos protein as a marker of neuronal activity and as to the stimulus specificity 
of Fos expression. Thus, the goals of this chapter are twofold. First, it will be 
discussed how the expression of c -fos can be used in the author’s system to 
identify which populations of spinal cord neurons are activated by noxious 
stimulation and to evaluate the effects of known analgesics on noxious 
stimulus-evoked Fos expression. Second, the question of stimulus specificity 
will be addressed by comparing the pattern of c -fos expression produced by 
nonnoxious as well as noxious stimuli. 
SPINAL CORD NOCICEPTIVE CIRCUITRY 
The authors’ analyses of the expression of the c -fos gene has been done 
primarily in the spinal cord dorsal horn. This region is the first CNS site for the 
transfer of nociceptive (i.e., pain) messages from the periphery and, thus, plays 
a key role in nociception. The dorsal horn has been divided on cytoarchitectural 
grounds into several discrete laminae, numbered I through VI from dorsal to 
ventral. High threshold (i.e., nociceptive) myelinated A-6 and unmyelinated C 
primary afferent fibers carry nociceptive information from the periphery to the 
dorsal horn; A-6 fibers synapse on neurons in lamina I, the outer portion of 
lamina II, and lamina V; C-fibers predominantly synapse on neurons in laminae 
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