Central mechanisms in the control of penile erection: Current theory and research

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Editorial
Central mechanisms in the control of penile erection: current theory and
research
Few aspects of normal physiology have fascinated and
captivated the popular imagination as much as penile erec-
tion. Beyond its obvious significance for copulation, the
erect phallus has served as a near-universal symbol of
male fertility, strength and sexual vigor in most cultures
throughout history. Scientific and professional interest in
the topic increased dramatically during the 1990’s,
however, driven in part by recognition of the widespread
prevalence of erectile disorders in the general population
[5,9], as well as the discovery of new drugs for the treatment
of erectile dysfunction (ED) [4,6,10,13]. Noting the poten-
tially devastating psychological effects of this disorder on
many men and their sexual partners, a special “consensus
conference” on the topic was convened by the National
Institutes of Health in 1992 [11]. Among the major recom-
mendations of this conference was the need for more basic
research on the physiological mechanisms of penile erec-
tion, particularly in regard to the neurovascular and hormo-
nal underpinnings. Significant progress has occurred
recently in understanding the local hemodynamic and
neurochemical processes involved in erection, specifically
the role of nitric oxide and other local neurotransmitters on
vasodilation and smooth muscle relaxation in the penile
corpora [1,3,14]. However, less attention has been given
to the role of central mechanisms, despite abundant clinical
examples of the importance of CNS disorders in the etiology
of ED [2,8,16]. Similarly, centrally-acting drugs have been
increasingly implicated in the etiology and/or treatment of
sexual disorders generally, including ED [7,12,15,17].
With these considerations in mind, a special invited
conference was convened on the topic of central mechan-
isms in the control of erection in Chicago, Illinois, in
December, 1998. This conference brought together, for
the first time, an international panel on the central neural
control of erection, comprising researchers and clinicians
involved in basic science and applied aspects of the
topic.
1
Six invited papers were presented at this meeting,
each covering specific aspects of central neural control:
neuroanatomy, neurophysiology, neurochemistry, and clin-
ical conceptualization and treatment of ED. The charge for
each presenter was to review existing theory and data in his
particular area of expertise, to identify key research ques-
tions and issues, and to propose new theoretical or research
models as needed. Extended panel discussions accompanied
each presentation. Following the meeting, presenters were
invited to revise and update their presentations for final
publication. The resulting papers make up the content of
this special supplement. The conference was funded by an
unrestricted educational grant from TAP Pharmaceuticals,
and was co-chaired by H. Padma-Nathan, I. Goldstein and
R. Rosen.
Despite obvious differences in focus and orientation
among the presenters, several broad generalizations
emerged from the formal presentations and subsequent
panel discussions. These were briefly as follows:
1. A spinal generator system exists for the control of erec-
tion that can be activated by the pudendal, pelvic and
possibly the hypogastric nerve afferents. The spinal
system is under inhibitory and excitatory modulatory
control from the brain. Ascending pathways modulate
activity or level setting of the supraspinal sites as well.
These ascending and descending pathways modulate the
spinal generator system at the level of the spinal inter-
neurons found in the intermediolateral column and dorsal
interneurons. However, there may exist direct suprasp-
inal projections to spinal efferents in addition to these
intermediary neurons. The neuroanatomical organization
of these pathways is described in detail in Steers’ paper in
this volume.
2. The central anatomical structures or networks involved in
the mediation of erection include the prefrontal cortex,
hippocampus, amygdala, hypothalamus, midbrain, pons
and medulla. Supraspinal sites that project directly to the
spinal cord generator include the paraventricular nucleus
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BIOBEHAVIORAL
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1
Panelists included: John Bancroft, MD, Indiana University; Francois
Giuliano, MD, Faculte de Medecine Paris SUD; Irwin Goldstein, MD,
Boston University, Jeremy Heaton, MD, Queens University; Ronald
Lewis, MD, Medical College of Georgia; Tom Lue, MD, University of
California at San Francisco; Kevin McKenna, Ph.D., Northwestern Univer-
sity Medical School; Harin Padma-Nathan, MD, University of Southern
California; Raymond Rosen, Ph.D., Robert Wood Johnson Medical School;
Benjamin Sachs, Ph.D., University of Connecticut; R. Taylor Segraves,
MD, Case Western Reserve; and William Steers, MD, University of Virgi-
nia School of Medicine.

(PVN), the locus coeruleus, nucleus paragigantocellu-
laris (NPGi), parapyramidal reticular formation, raphe
magnus, raphe pallidus, A5-adrenergic cell group and
Barrington’s nucleus. At least some of the supraspinal
anatomical centers and pathways involved in the control
of erection are organized in distributed (or parallel) form,
rather than hierarchically.
3. Among the major neurotransmitters involved in the
supraspinal control of erection are dopamine, norepi-
nephrine, serotonin, oxytocin, glutamate, and other
neuropeptides and hormones. Dopamine, in particular,
has localized activity in the PVN and medial preoptic
area and is excitatory to oxytocinergic pathways that
project to the spinal erection generator. Norepinephrine
receptors in the locus coeruleus are similarly involved in
the central activation of sexual arousal, whereas seroto-
nin (5-HT
2
) receptors in the NPGi have a largely inhibi-
tory role. Steroid hormones (testosterone, estrogen) serve
as important neuromodulators of these effects, in ways
that are not fully understood at present. The peripheral
nerve supply, including the pelvic/cavernous, pudendal/
dorsal penile, and hypogastric nerves, are generally
mixed in neurotransmitter type, in contrast to the tradi-
tional conceptualizations of these nerves as sympathetic
vs. parasympathetic, or somatic vs. autonomic. The role
of specific neurotransmitters is reviewed by Giuliano and
Rampin, and McKenna.
4. The neurophysiological processes and mechanisms of
penile erection vary depending upon the specific envir-
onment or stimulus context in which sexual arousal takes
place. Based upon these findings, a new classification
system has been proposed to replace the traditional clas-
sification of erections as “psychogenic” or “reflexo-
genic”. This issue is addressed in depth in the
accompanying paper by Sachs, who also raises questions
about the current taxonomy of ED.
5. Central excitation and inhibition of sexual arousal may
be conceptualized at a psychological, as well as a neuro-
physiological level. Based upon recent questionnaire
findings from large samples of sexually functional and
dysfunctional males, one excitatory and two central
inhibitory factors have been postulated. These factors
have been correlated with neurophysiological findings
in a series of studies reviewed by Bancroft and
Janssen in this volume. This paper also provides a
reconceptualization of the role of psychological
processes in ED.
6. Finally, centrally active pharmacological agents are in
development for the management of ED and other sexual
disorders. Apomorphine, a combined D
1
/D
2
agonist, has
been extensively studied as a pro-erectile agent in both
human and animal studies, as described by Heaton.
Results of recent studies in men with erectile dysfunction
show the drug to be moderately effective and generally
well tolerated. Other centrally active agents are in devel-
opment and will undoubtedly play an increasingly
important role in the future management of sexual disor-
ders in men and women.
In summary, exploration of central mechanisms in the
control of penile erection is an exciting, challenging and
growing area of neuroscience research. Each of the papers
in this collection provides fresh insights to old questions
about the nature and significance of penile erection in
human and non-human species. In addition to increasing
our understanding of the underlying mechanisms and
processes of sexual response, the implications of the
research reviewed here hold promise for developing novel
therapeutic alternatives for the treatment of common sexual
disorders. Many questions remain to be addressed in this
rapidly evolving research area, as one of the important
goals of the conference was to identify key issues and ques-
tions for further study. We hope that the accompanying
papers will serve as a stimulus to further basic and applied
research on this highly relevant and largely under-
researched topic.
References
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Raymond C. Rosen
Benjamin D. Sachs
Department of Psychiatry,
Robert Wood Johnson Medical School,
675 Hoes Lane,
Piscataway, NJ 08854-5635, USA
E-mail address: rosen@umdnj.edu
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