The role of serotonin in modulation of nociceptive reflexes.

Abstract

During the past fifteen years, a variety of evidence has accumulated which is consistent with the Brodie and Shore (1957) hypothesis that serotonergic neurons in the central nervous system serve a tropotrophic role (Hess, 1954) in inhibiting an animal’s response to diverse arousing stimuli (Harvey et al., 1975). This role for serotonin is, perhaps, most thoroughly documented in studies dealing with an animal’s response to painful stimuli. The results of numerous studies suggest that decreases in serotonergic activity result in hyperalgesia while increases produce analgesia (Harvey et al., 1975; Mayer and Price, 1976; Messing and Lytle, 1977). Thus one can assume that painful stimuli normally lead to increased activity within the serotonergic system which partially inhibits or diminishes the intensity of the nociceptive reflex. This view of the role of serotonin in determining an animal’s response to painful stimuli has resulted from the application of a wide variety of techniques for altering serotonergic function in the central nervous system and for assessing pain sensitivity. Such a convergent approach is important, since no single technique can be relied on to produce an alteration in serotonergic function without also having additional effects, some of which are known and others yet to be discovered. Similarly, since pain is not a unitary phenomenon, there is no a priori reason for assuming that serotonin should have an equivalent inhibitory effect on all nociceptive reflexes. In fact, since different nociceptive reflexes involve different portions of the central nervous system, it would be more surprising if some form of selectivity did not exist. Most investigators, including ourselves, have sometimes ignored these caveats by placing too great a reliance on a single procedure for altering serotonergic function or for assessing pain sensitivity. As a result the precise role of serotonin in determining an animal’s response to painful stimuli has recently been obscured by conflicting conclusions and apparently contradictory data. Accordingly, this paper will review the evidence concerning the role of serotonin in nociception, with special attention given to the means employed for altering serotonergic function and assessing pain sensitivity.