RETICULAR FORMATION 1
RETICULAR FORMATION: ORGANIZATION
The reticular formation, RF, is the name for a group of
neurons found throughout the brainstem. Using the ventral
view of the brainstem, the reticular formation occupies
the central portion or core area of the brainstem from
midbrain to medulla (see also brainstem cross-sections in
Figure 65–Figure 67).
This collection of neurons is a phylogenetically old
set of neurons that functions like a network or reticulum,
from which it derives its name. The RF receives afferents
from most of the sensory systems (see next illustration)
and projects to virtually all parts of the nervous system.
Functionally, it is possible to localize different subgroups
within the reticular formation:
• Cardiac and respiratory “centers”: Subsets
of neurons within the medullary reticular formation
and also in the pontine region are
responsible for the control of the vital functions
of heart rate and respiration. The importance of
this knowledge was discussed in reference to
the clinical emergency, tonsillar herniation
(with Figure 9B).
• Motor areas: Both the pontine and medullary
nuclei of the reticular formation contribute to
motor control via the cortico-reticulo-spinal
system (discussed in Section B, Part III, Introduction;
also with Figure 49A and Figure 49B).
In addition, these nuclei exert a very significant
influence on muscle tone, which is very important
clinically (discussed with Figure 49B).
• Ascending projection system: Fibers from the
reticular formation ascend to the thalamus and
project to various nonspecific thalamic nuclei.
From these nuclei, there is a diffuse distribution
of connections to all parts of the cerebral cortex.
This whole system is concerned with consciousness
and is known as the ascending reticular
activating system (ARAS).
• Pre-cerebellar nuclei: There are numerous
nuclei in the brainstem that are located within
the boundaries of the reticular formation that
project to the cerebellum. These are not always
included in discussions of the reticular formation.
It is also possible to describe the reticular formation
topographically. The neurons appear to be arranged in
three longitudinal sets; these are shown in the left-hand
side of this illustration:
• The lateral group consists of neurons that are
small in size. These are the neurons that receive
the various inputs to the reticular formation,
including those from the anterolateral system
(pain and temperature, see Figure 34), the
trigeminal pathway (see Figure 35), as well as
auditory and visual input.
• The next group is the medial group. These
neurons are larger in size and project their
axons upward and downward. The ascending
projection from the midbrain area is particularly
involved with the consciousness system. Nuclei
within this group, notably the nucleus gigantocellularis
of the medulla, and the pontine reticular
nuclei, caudal (lower) and oral (upper)
portions, give origin to the two reticulo-spinal
tracts (discussed with the next illustration, also
Figure 49A and Figure 49B).
• Another set of neurons occupy the midline
region of the brainstem, the raphe nuclei,
which use the catecholamine serotonin for neurotransmission.
The best-known nucleus of this
group is the nucleus raphe magnus, which plays
an important role in the descending pain modulation
system (to be discussed with Figure 43).
In addition, both the locus ceruleus (shown in the
upper pons) and the periaqueductal gray (located in the
midbrain, see next illustration and also Figure 65 and
Figure 65A) are considered part of the reticular formation
(discussed with the next illustration).
In summary, the reticular formation is connected with
almost all parts of the CNS. Although it has a generalized
influence within the CNS, it also contains subsystems that
are directly involved in specific functions. The most clinically
significant aspects are:
• Cardiac and respiratory centers in the medulla
• Descending systems in the pons and medulla
that participate in motor control and influence
• Ascending pathways in the upper pons and midbrain
that contribute to the consciousness system
RETICULAR FORMATION 3
PAIN MODULATION SYSTEM
Pain, both physical and psychic, is recognized by the
nervous system at multiple levels. Localization of pain,
knowing which parts of the limbs and body wall are
involved, requires the cortex of the postcentral gyrus (SI);
SII is also likely involved in the perception of pain (discussed
with Figure 36). There is good evidence that some
“conscious” perception of pain occurs at the thalamic
We have a built-in system for dampening the influences
of pain from the spinal cord level — the descending
pain modulation pathway. This system apparently functions
in the following way: The neurons of the periaqueductal
gray can be activated in a number of ways. It is
known that many ascending fibers from the anterolateral
system and trigeminal system activate neurons in this area
(only the anterolateral fibers are being shown in this illustration),
either as collaterals or direct endings of these
fibers in the midbrain. This area is also known to be rich
in opiate receptors, and it seems that neurons of this region
can be activated by circulating endorphins. Experimentally,
one can activate these neurons by direct stimulation
or by a local injection of morphine. In addition, descending
cortical fibers (cortico-bulbar) may activate these neurons
(see Figure 46).
The axons of some of the neurons of the periaqueductal
gray descend and terminate in one of the serotonincontaining
raphe nuclei in the upper medulla, the nucleus
raphe magnus. From here, there is a descending, crossed,
pathway, which is located in the dorsolateral white matter
(funiculus) of the spinal cord. The serotonergic fibers terminate
in the substantia gelatinosa of the spinal cord, a
nuclear area of the dorsal horn of the spinal cord where
the pain afferents synapse (see Figure 32). The descending
serotonergic fibers are thought to terminate on small interneurons,
which contain enkephalin. There is evidence that
these enkephalin-containing spinal neurons inhibit the
transmission of the pain afferents entering the spinal cord
from peripheral pain receptors. Thus, descending influences
are thought to modulate a local circuit.
There is a proposed mechanism that these same interneurons
in the spinal cord can be activated by stimulation
of other sensory afferents, particularly those from the
touch receptors in the skin and the mechanoreceptors in
the joints; these give rise to anatomically large well-myelinated
peripheral nerve fibers, which send collaterals to the
dorsal horn (see Figure 32). This is the physiological basis
for the gate theory of pain. In this model, the same circuit
is activated at a segmental level.
It is useful to think about multiple gates for pain
transmission. We know that mental states and cognitive
processes can affect, positively and negatively, the experience
of pain and our reaction to pain. The role of the
limbic system and the “emotional reaction” to pain will
be discussed in Section D.
In our daily experience with local pain, such as a bump
or small cut, the common response is to vigorously rub
and/or shake the limb or the affected region. What we may
be doing is activating the local segmental circuits via the
touch- and mechano-receptors to decrease the pain sensation.
Some of the current treatments for pain are based upon
the structures and neurotransmitters being discussed here.
The gate theory underlies the use of transcutaneous stimulation,
one of the current therapies offered for the relief
of pain. More controversial and certainly less certain is
the postulated mechanism(s) for the use of acupuncture
in the treatment of pain.
Most discussions concerning pain refer to ACUTE
pain, or short-term pain caused by an injury or dental
procedure. CHRONIC pain should be regarded from a
somewhat different perspective. Living with pain on a
daily basis, caused, for example, by arthritis, cancer, or
diabetic neuropathy, is an unfortunately tragic state of
being for many people. Those involved with pain therapy
and research on pain have proposed that the CNS actually
rewires itself in reaction to chronic pain and may in fact
become more sensitized to pain the longer the pain pathways
remain active; some of this may occur at the receptor
level. Many of these people are now being referred to
“pain clinics,” where a team of physicians and other health
professionals (e.g., anesthetists, neurologists, psychologists)
try to assist people, using a variety of therapies, to
alleviate their disabling condition.