Department of Physiological Sciences, College of Veterinary Medicine, and University of Florida Brain Institute, University of Florida, Gainesville, Florida 32610-0144
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ABSTRACT |
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Hubscher, Charles H. and Richard D. Johnson. Effects of Acute and Chronic Midthoracic Spinal Cord Injury on Neural Circuits for Male Sexual Function. I. Ascending Pathways. J. Neurophysiol. 82: 1381-1389, 1999. Normal male reproductive function, particularly ejaculation, requires the integrity of urogenital sensory input and its ascending spinal projections. After midthoracic chronic spinal cord injury, sexual dysfunction occurs in both rats and humans. Neurons in the medullary reticular formation (MRF) are involved in the processing of bilaterally convergent sensory inputs from multiple cutaneous, mucocutaneous, and visceral regions of the body, including the penis and male urogenital tract. A variety of acute and chronic lesions were used to determine the midthoracic location of ascending spinal pathways conveying sensory input from the penis and male urogenital tract to MRF. A total of 371 single neurons were recorded in the MRF of 34 urethan-anesthetized mature male rats. Twenty-seven rats received a chronic T8 dorsal (DHx) or lateral (LHx) hemisection or contusion (Cx) injury 30 days before the terminal electrophysiological experiments. In addition, nine dorsal nerve of the penis (DNP)-responsive MRF neurons in seven intact control animals were tested completely both before and after various select acute spinal cord lesions. The chronic lesion data indicate that low and high threshold input from the penis (mucocutaneous) and male urogenital tract (visceral) ascend bilaterally within the dorsal quadrant at T8 as opposed to high threshold input from the hindpaws (cutaneous), which ascends unilaterally in the ventrolateral quadrant (VLQ). The acute lesion data indicate that the low-threshold information conveyed from the penis and male urogenital tract ascends in the dorsal columns, as opposed to the high-threshold nociceptive inputs that ascend bilaterally in the dorsolateral quadrant (DLQ). These results, as well as previous data on ascending projections from female reproductive organs within the dorsal columns and DLQ to other caudal brain stem nuclei, provide evidence for ascending pathways conveying nociceptive information centrally via the DLQ. This spinal gray-DLQ pathway(s) conveying information from mucocutaneous/pelvic/visceral territories therefore differs from the traditionally recognized spinal gray-VLQ pathway(s), which is known to convey nociceptive information from cutaneous regions of the body.
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INTRODUCTION |
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The peripheral sensory limb of the segmental
reflexes for erection and ejaculation is carried primarily by afferents
in the dorsal nerve of the penis (DNP) (Johnson 1988;
McKenna and Nadelhaft 1986
; Rampin et al.
1994
). Desensitization of the penis, produced by local
anesthesia or dorsal nerve section, causes an impairment of
reflexogenic erection, intromission, and ejaculation (reviewed in
Sachs and Meisel 1988
). The primary afferent population
in the DNP has been characterized (Johnson and Halata
1991
; Johnson and Murray 1992
;
McKenna and Nadelhaft 1986
; Nunez et al.
1986
; Steers et al. 1988
). Electrophysiological
techniques have been used to investigate single spinal cord
interneurons in the dorsal horn and intermediate zone of primarily
L6-S1 that receive input from these DNP afferents (Johnson 1989
). All of the
penile interneurons exhibit receptive fields on the penis that are
significantly larger than the receptive fields for single primary
afferent neurons, thereby demonstrating a central convergence of penile
sensory input. Almost all of the penile interneurons have receptive
fields on both sides of the body, and their electrical characteristics strongly suggest a monosynaptic input from both ipsilateral and contralateral DNP fibers (Johnson 1989
).
DNP afferents produce bilateral (crossed and uncrossed) reflex
facilitation of pudendal motoneurons. The synaptic efficacy of DNP
afferents and associated interneurons onto pudendal motoneurons is
reduced progressively over time in rats with chronic spinal cord
injuries (Johnson 1994). The enhanced erectile and
depressed ejaculatory reflexes in rats after midthoracic transection
and 30 days recovery (Hart and Odell 1981
; Mas et
al. 1987
; Sachs and Garinello 1979
) is likely
due to a loss of supraspinal influences. Thus the pudendal afferent
facilitation of ejaculation may require a brain stem loop, much like
the control of micturition (deGroat et al. 1981
).
Previous studies show that the nucleus reticularis gigantocellularis
and surrounding nuclei, located in the medullary reticular formation
(MRF), are likely involved in this supraspinal loop (Marson and
McKenna 1990; Marson et al. 1993
; Tanaka
and Arnold 1993
; Yells et al. 1992
). The MRF
contains many neurons responsive to bilateral DNP stimulation
(Hubscher and Johnson 1996a
). The majority of
these neurons are responsive to mechanical stimulation (majority
high-threshold) of the penis, especially the distal glans/cup region.
Almost half of the neurons also respond to bilateral pelvic nerve (PN)
stimulation and receive convergent inputs from several cutaneous
regions of the body outside the pelvic/pudendal nerve territory,
including the hindfeet, forefeet, and ears. Furthermore bilateral
electrical stimulation of specific DNP-responsive MRF subregions
suppress DNP-mediated pudendal motoneuron reflex discharges (Johnson and Hubscher 1998
) and activate sympathetic
fibers in the pudendal nerve (Johnson and Hubscher
1997
).
The location of the ascending and descending spinal projections
comprising the supraspinal loop between the lumbosacral ejaculatory circuitry and the MRF is unknown. In the present study, the spinal cord
location of ascending projections within the midthoracic white matter
was examined by recording MRF neurons either immediately or 30 days
after a variety of spinal lesions. Chronic lesions included dorsal
(DHx) or lateral (LHx) hemisection, or contusion injury (Cx; severe or
moderate). The data from animals with chronic hemisection lesions are
compared with the acute controls. Changes in receptive fields at or
above the level of lesion have been reported elsewhere for this same
group of animals (Hubscher and Johnson 1999).
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METHODS |
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Chronic spinal cord lesions
A total of 27 male Wistar rats (age of ~90 days) received one
of three types of spinal cord injury at T8: DHx,
LHx, or Cx. The T8 level of spinal cord was
chosen because it is rostral to the spinal reflex centers for erection
and ejaculation and it is caudal enough to ensure stability and
survivability of all groups of animals for the duration of the
experiment. The recovery period for each animal was 30 days. At the end
of the recovery period, each animal was anesthetized and the terminal
electrophysiological experiment performed according to the protocol
outlined in following text. Lesion surgeries were performed under
aseptic conditions. Each animal (~90 days of age) was anesthetized
with a mixture of ketamine (80 mg/kg ip) and xylazine (10 mg/kg ip). A
long-acting antibiotic (Flo-Cillin: 0.5 ml; Fort Dodge Laboratories,
Fort Dodge, IA) was administered before surgery. The spinal cord was exposed at the T8 level via removal of the
overlying T7 vertebral lamina. Hemisections (DHx
or LHx) were made through a longitudinal dural incision using a pair of
microdissecting scissors. The dura was closed with a pair of 10-0
monofilament sutures. Contusion of the spinal cord was performed using
a rapid compression of the T8 cord with a concave
probe having a radius and size matching the overlying lamina. The probe
was attached to a displacement-controlled mechanostimulator
(Chubbuck 1966) driven with a trapezoid waveform using
severe contusion parameters (1.9-2.0 mm, 5 s) modified from previously described protocols (Bresnahan et al. 1987
;
Theriault and Tator 1994
). Thrombin-soaked absorbable
gelatin sponge (Gelfoam) was placed into the vertebral defect.
The surrounding musculature and subcutaneous tissue were sutured in
layers with 4-0 monofilament. The skin was closed with Michel clips.
The animals recovered in a temperature-controlled environment while housed singly in plastic cages with wood chips. An analgesic (Buprenex) was administered as needed to alleviate postoperative discomfort. During the first postoperative day, the animals were encouraged to eat with apple slices. Throughout the recovery period the animals were tended to three times daily, 7 days a week. At these times, the animals were exercised, washed, and observed for evidence of infection or other complications, and the bladder expressed until reflex voiding function returned (6-12 days).
Surgical preparation for terminal electrophysiological experiments
Seven uninjured male Wistar rats at ~120 days of age were used
in the acute lesion experiments. The remaining 27 rats had a chronic
injury for 30 days before the terminal experiment. Using our previously
described protocol (Hubscher and Johnson 1996a), each
animal was anesthetized with urethan (1.2 g/kg ip). Supplements were
given as needed. The common carotid artery, jugular vein, and trachea
were intubated for the purposes of blood pressure monitoring,
intravenous infusion route, and facilitation of respiration, respectively. Body temperature was maintained at 37°C through an
esophageal thermistor and circulating water heating pad/body coils. The
ventilatory state was monitored with an end tidal
pCO2 monitor designed for rodents. Mean blood
pressure was maintained at
75 mmHg throughout the experiment.
The head was clamped in a stereotaxic holder and the brain stem exposed
as previously described (Hubscher and Johnson 1996a). The ventral aspect of the pelvic region was swung caudally by pivoting
the hindquarters around the axis through the hip pins and tying the
tail in an upward direction. This positioning allowed the penis,
ventral abdomen, and perineum to be exposed for stimulation. Specially
fabricated bipolar silicon-cuff microelectrodes were placed bilaterally
around the dorsal nerve of the penis (DNP), pelvic nerve (PN), and the
proximal cut end of the deep perineal (motor branch of the
pudendal) nerve (see experimental setup in Fig. 1 of Hubscher and
Johnson 1996a
).
Electrophysiological recordings
Glass-coated platinum-plated tungsten microelectrodes with a
20-µm exposed tip (Merrill and Ainsworth 1972)
attached to a stepping microdrive were used as previously described
(Berkley et al. 1993a
; Hubscher and
Berkley 1994
; Hubscher and Johnson 1996a
). Two
microelectrodes were set for bilateral penetration of the MRF, in the
same anterior/posterior plane and equidistant to the midline. Four
stereotaxic equivalent tracks in the "hottest" DNP/PN responsive
MRF region (see Fig. 1A in Hubscher and Johnson 1999
) was searched for neurons responsive bilateral stimulation of the DNP, as well as pinching of the ears. Ear pinch (unilateral; alternating between left and right sides) was applied as infrequently as possible (every 200 µm and/or when a spontaneously active neuron was encountered) to reduce potential sensitization/tissue damage. Note
that the search protocol was altered from being just bilateral DNP
stimulation (Hubscher and Johnson 1996a
) due to the loss
(or potential loss) of DNP inputs below the level of lesion after chronic spinal cord injury. The ear was chosen because the input pathway enters the CNS above T8 (lesion level) and, in
intact controls, almost all DNP-responsive MRF neurons respond to
pinching of the ears (Hubscher and Johnson 1996a
).
Acute spinal cord lesions
After the characterization of the last DNP-responsive MRF neuron
in each of the seven uninjured animals, a partial
T7-T8 spinal cord lesion
was made with microscissors, and the response characteristics were
redetermined (Berkley and Hubscher 1995). This process
was repeated with each of three additional lesions, all placed at different rostrocaudal sites in the
T7-T8 spinal cord to
facilitate postmortem acute lesion reconstruction. A typical sequence
is illustrated in Fig. 1. In two animals,
simultaneous unit recordings from both electrodes allowed for study of
two units through the lesioning process.
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Histology
At the end of the experiment, the animal was euthanatized with
an anesthetic overdose and perfused transcardially with 0.9% saline
followed by 10% formalin. The block of brain stem tissue containing
the recording sites was removed and stored overnight in a 10%
formalin/30% sucrose solution. Recording sites were visualized in
50-µm vibratome sections stained with cresyl violet and reconstructed under light and dark field illumination (Paxinos and Watson
1997). The perfused spinal cord was analyzed histologically
(paraffin sections) for confirmation of acute or chronic lesion extent. Spinal cord tissue sections were stained with both luxol fast blue and
cresyl violet (Kluver-Barrera stain).
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RESULTS |
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Acute spinal cord lesions
A total of nine DNP-responsive neurons were tested in the
uninjured rats (n = 7) before and after acute
midthoracic spinal lesions. Before a lesion was made, three of the MRF
neurons tested had excitatory responses to gentle stroking [a
low-threshold (LT) stimulus] and pinching [high-threshold (HT)
stimulus] of the glans penis. After an acute lesion, which included
the dorsal columns (see Fig. 2,
left), LT responses were eliminated; high-threshold (HT)
responses remained. Bilateral lesions, which included the dorsal
lateral quadrant (DLQ; see Fig. 2, right) were necessary for
elimination of the HT DNP responses (see example in Fig. 1). However,
MRF neuronal responses remained for bilateral pinching of the toes
(except in a few cases where the lesion encroached on the ventrolateral
quadrantVLQ: see left side of lesion and responses in Fig. 1) as well
as bilateral pinching of the ears and forepaws.
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Chronic spinal cord lesions
A total of 27 male rats received a midthoracic spinal cord lesion
30 days before terminal electrophysiological experiments. The results
of these experiments relative to the presence or absence of responses
from convergent territories originating from regions below the level of
injury onto single MRF neurons are summarized in Table
1 and described in more detail in the
following text. A total of 362 single neurons responded to bilateral
DNP and/or ear stimulation. Neurons responding to bilateral DNP
stimulation were found among the LHx (83%), DHx (30%), and moderate
Cx (83%) groups. The effects of these chronic lesions on the responses of cutaneous convergent territories located at or above the level of
injury are presented elsewhere (Hubscher and Johnson
1999).
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CHRONIC CONTUSION INJURIES.
The MRF of 10 rats was searched for neurons responsive to bilateral
electrical stimulation of the DNP and gentle pressure of the ears 30 days after Cx injury. Histological examination of the spinal cords at
the epicenter of the Cx injury revealed severe damage in 6 of the 10 cases studied (see typical example in photomicrograph Fig.
3A). In the six rats with
severe Cxs, no DNP-responsive neurons were found. However, many
neuronal responses were found for stimulation of the ears
(n = 66), and the majority responded to more gentle
levels of stimulation than had been observed in intact controls
(Hubscher and Johnson 1996a). A typical example of
responses is shown in Fig. 4. No
responses were found for bilateral PN stimulation or the toes of the
hindfeet (pinch), which were tested frequently in addition to the
search stimuli (i.e., bilateral DNP and ears).
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CHRONIC DORSAL HEMISECTIONS. The MRF of nine rats was searched for neurons responsive to bilateral electrical stimulation of the DNP and gentle pressure of the ears 30 days after T8 DHx. Histological examination of the spinal cord sections at the epicenter of the lesion revealed five of nine cases where the DHx was complete bilaterally; i.e., the lesion extended down to or just beyond the dorsal limit of the ventral quadrant on both sides of the cord. In the five animals with complete DHxs (see typical example in Fig. 3C), many MRF neuronal responses were found for stimulation of the ears (n = 79) but only a few responses remained (7%) for bilateral DNP and bilateral PN stimulation and their respective peripheral territories. Unlike the chronic contusion injuries, however, responses remained for pinching of the toes of the hindfeet bilaterally (see example in Fig. 5). In the four cases with incomplete DHxs, many ear responsive single MRF neurons also were found (n = 43); however, the majority of these (70%) responded to bDNP stimulation, which is why the overall value shown in Table 1 is so high.
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CHRONIC LATERAL HEMISECTIONS. The MRF of eight rats was searched for neurons responsive to bilateral electrical stimulation of the DNP and gentle pressure of the ears 30 days after lateral T8 hemisection. Histological examination of the spinal cord sections at the epicenter of the lesion revealed three cases where the lesion was complete unilaterally and did not encroach on the contralateral dorsal columns or spinal gray matter. In two other cases, the lesion was complete unilaterally but in addition impinged on the contralateral dorsal columns and spinal gray. For the remaining three cases, which also were complete unilaterally, the lesion again impinged on the contralateral dorsal columns and spinal gray, but in addition a portion of the contralateral white matter was damaged (1 typical example is shown in Fig. 3D). However, regardless of these histological differences, all eight animals with complete or overlateral chronic hemisections had many MRF neurons 30 days postinjury that responded to both ipsilateral and contralateral stimulation of the DNP and PN. These MRF neuronal responses occurred regardless of whether their brain stem location was ipsilateral or contralateral to the side of the lesion.
Overall, both the number of DNP-responsive neurons and their response properties did not differ significantly from intact controls throughout equivalent tracks (see Table 1 and example in Fig. 6). However, differences in degree of convergence and magnitude of responses were observed between LHx animals and intact controls. For example, DNP-responsive MRF neurons did not respond to pinching the toes of the hindpaw that was contralateral to the side of the lesion, regardless of MRF neuronal location (i.e., ipsilateral or contralateral to the lesion). Also, the magnitude and duration of MRF neuronal responses was greatest for bilateral peripheral nerve stimulation (of the DNP and PN), as was the case for intact controls (Hubscher and Johnson 1996a
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DISCUSSION |
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The results of the present study demonstrate the presence of MRF neuronal responses to inputs from the male genitalia after either a chronic LHx or a moderate Cx injury (i.e., with at least 1 spared lateral rim of white matter) and the absence of these responses after either a severe chronic Cx injury or a complete chronic DHx. When taken together, the results suggest that the ascending spinal projections originating from the male genitalia are bilateral and are located within the dorsal quadrant at the midthoracic level of the spinal cord. The results of these chronic lesion experiments were confirmed with select acute lesions, which showed the small number of LT penile inputs to the MRF projected rostrally via the dorsal columns versus the more numerous HT inputs that projected bilaterally within the DLQ.
The present study also demonstrates the presence of bilateral inputs
from cutaneous/mucocutaneous/visceral territories innervated by either
the DNP or PN to MRF neurons on both sides of the brain stem after an
LHx. Whereas cutaneous inputs from previously responsive territories
caudal to the spinal cord injury were only maintained from the side
ipsilateral to the lesion (i.e., for toes of the hindfoot),
mucocutaneous/visceral inputs were maintained from both sides of the
body, although there was a predominance from the side ipsilateral to
the lesion. When taken together, the results indicate a truly bilateral
system from the penis and male urogenital tract in which information
about noxious stimuli applied to mucocutaneous and visceral tissues is
conveyed via spinal dorsal horn neurons on both sides of the spinal
cord and ascends bilaterally through the DLQ at the midthoracic level
of the spinal cord to synapse, either directly or indirectly, onto MRF
neurons on both sides of the brain stem (see summary diagram in Fig.
7 and further discussion in the following
text). In addition, these results confirm and expand on a previous
report investigating central projections originating from female
reproductive organs (Berkley and Hubscher 1995;
Hubscher and Berkley 1995
); i.e., that the classical
"pain pathways" within the VLQ are not the only neurons through
which nociceptive information can be conveyed centrally.
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Dorsal nerve of the penis-responsive MRF neurons
Responses of MRF neurons to inputs from the male genitalia via the DNP were eliminated after chronic DHx and after acute dorsal quadrant lesions. The MRF responses from both the left and right DNP were not eliminated after an acute unilateral lesion of the dorsal quadrant at the midthoracic level of spinal cord or after chronic LHx, although the magnitude and/or duration of the majority of MRF neuronal responses was greater from the DNP that was located ipsilateral to the LHx. These results indicate that the projections from the lumbosacral spinal cord originating from the DNP are bilateral with a contralateral predominance.
Pelvic nerve-responsive MRF neurons
Chronic bilateral DHx eliminated MRF neuronal responses to bilateral electrical stimulation of the PN. In contrast, chronic LHx failed to eliminate MRF neuronal responses on either side of the brain stem. Although these neurons responded to stimulation of the PN's innervating both sides of the body, there was a definite contralateral predominance; i.e., MRF neurons (on either side of the brain stem) responding mostly to the PN ipsilateral to the LHx, although the largest magnitude and/or duration of response was to bilateral PN. These results, when taken together, indicate that unilateral spinal projections in the DLQ at midthoracic spinal cord conveys information from both PNs (with a contralateral predominance) and that the projections are crossed and uncrossed above the lesion.
MRF inputs from skin
Chronic severe Cx was the only injury to eliminate bilateral responses to noxious mechanical stimulation of the skin of the hindlimb (such as pinching the toes of the hindfoot). Responses to cutaneous territories were lost unilaterally after either a chronic LHx or cases where only a lateral rim of white matter remained (i.e., after a chronic moderate Cx injury). In addition, unlike the loss of responses to stimulation of the male urogenital tract after a chronic DHx, MRF neuronal responses remained for stimulation of the distal hindlimb skin (i.e., for regions that responded in intact controls). These results, when taken together, indicate that unilateral spinal-MRF projections in the VLQ at the midthoracic level convey information primarily from contralateral distal hindlimb cutaneous regions.
Location of ascending pathways
DORSAL NERVE OF THE PENIS. Although the majority of MRF responses to stimulation of the penis were elicited by firm pressure or pinch, a small number of neurons was excited by both stroking and pinching the penis. An acute bilateral lesion of the dorsal columns eliminated responses to stroking the penis, whereas the responses to pinching were maintained (and only eliminated after a subsequent bilateral DLQ lesion). These results suggest that the LT-DNP inputs are conveyed centrally via the dorsal columns, whereas the HT-DNP inputs are conveyed bilaterally within the DLQ. The results from the acute lesion experiments are consistent with those of the chronic ones, where a complete DHx eliminated all MRF neuronal responses to DNP stimulation, further evidence that these projections ascend bilaterally within the DLQ.
PELVIC NERVE.
Because the chronic DHx lesions included both the DLQ and dorsal
columns, it is uncertain which of these pathways contains rostral
projections from the PNs. Previous studies suggest that the central
projections of nociceptive inputs from visceral territories ascend via both pathways. These findings are different from an independent LT and HT pathway (dorsal column and DLQ, respectively), as
determined for the penis, i.e., mucocutaneous tissue (Johnson and Halata 1991) innervated by the DNP. The existence of
ascending projections conveying visceral PN inputs within one or both
pathways is likely dependent on one or more factors. Possibilities
include the type of stimulus (mechanical, thermal, and chemical), the type of tissue and its function, the tissues embryonic origin, the
location of the dorsal horn interneurons (laminae and/or spinal level),
and the location of the target nucleus in the brain stem. In support of
the importance of both dorsal column and DLQ pathways, neurons in the
nucleus gracilis failed to respond to uterine distention and colorectal
distension [conveyed centrally primarily via hypogastric and pelvic
nerves, respectively (Berkley et al. 1993b
)] after an
acute lesion of the dorsal columns (Al-Chaer et al.
1996
; Berkley and Hubscher 1995
). However, the
same lesions did not eliminate noxious inputs from the cervix and
vaginal canal (Berkley and Hubscher 1995
) [i.e., those
organs whose DRG supply is located primarily at the lumbosacral spinal
level (Berkley et al. 1993b
)]. Similar to inputs from
the male genitalia, noxious inputs from the cervix and vaginal canal to
the caudal brain stem in female rats were eliminated with an acute
bilateral DLQ lesion, although the neuronal response properties were
affected by a prior lesion of the dorsal columns (Berkley and
Hubscher 1995
).
SKIN.
The presence of cutaneous receptive fields (e.g., on both hindfeet)
after a chronic DHx confirms previous work on acute-lesioned animals
(reviewed by Willis and Coggeshall 1991), indicating
that mechanical nociceptive information conveyed from the skin ascends within the VLQ to MRF (either directly or indirectly). The data obtained from the chronic LHx group of animals also confirms that the
ascending pathways from skin are primarily from the contralateral side
of the body, once again being consistent with early studies demonstrating a predominantly unilateral pathway composed of dorsal horn cells that project across the midline and then ascend rostrally. However, because neurons on both sides of the MRF respond to unilateral inputs from the skin (as was the case after LHx), there is both a
crossed and uncrossed projection above the level of injury. The point
at which the information crosses the midline (for inputs from skin and
the male urogenital tract) is not yet known (Fig. 7).
Ascending pathways: direct or indirect?
The results of the present study indicate that central projections
originating from the male genitalia, conveyed rostrally from
lumbosacral dorsal horn cells to MRF, are located in the DLQ. At the
present time, it is unclear whether these projections reach the MRF
directly or indirectly via one or more synaptic contacts in other
regions of the brain. There is little evidence in the literature that
would strongly support or refute either of the two possibilities. For
example, the location of direct spinoreticular projections ascending in
the white matter of the rat spinal cord is unknown, with the exception
of one anatomic study that used large bulbar injections of horseradish
peroxidase to demonstrate the loss of retrogradely labeled
L4-L6 cells around the
central canal after a VLQ lesion at T12
(Nahin et al. 1986). The evidence from that study
relative to the present one in terms of consistency or the lack of is
inconclusive because the lesions appeared to encrouch on the ventral
portion of the DLQ, the lesions were at T12
(T7/T8 in the present
study) and there is evidence for a dorsal shift of axons as they ascend
rostrally (Willis and Coggeshall 1991
), and the study
focused on cells adjacent to the central canal, which are some of many
dorsal horn neurons to project directly on neurons in the MRF
(Chaouch et al. 1983
; Menetrey et al.
1980
) and respond to bilateral DNP (Johnson
1989
). There is also evidence for the existence of several
different ascending pathways within the DLQ of the rat, any of which
could provide indirect projections to MRF and thus may convey both
mucocutaneous and visceral information. Such pathways include a
spinomesencephalic pathway (McMahon and Wall 1983
;
Zemlan et al. 1978
) and a spinohypothalamic pathway
(Kostarczyk et al. 1997
).
Chronic versus acute data
The acute multilesion data yielded valuable information regarding immediate changes in MRF neuronal response status to a variety of peripheral inputs. Such information included ascending penile inputs in both the dorsal columns and DLQ (i.e., due to the loss of LT penile responses after dorsal column lesions and HT responses after DLQ lesions) and the need for a bilateral lesion to eliminate mucocutaneous and visceral responses. The chronic lesion data yielded valuable information regarding long-term changes in responses of MRF neurons to peripheral inputs after different kinds/extents of spinal cord injury. The results from these studies, also at the midthoracic level of spinal cord, were consistent with those after acute lesions, with one exception being that a slightly deeper DLQ lesion was necessary to eliminate MRF responses to stimulation of the DNP bilaterally. This chronic lesion depth, as depicted in Fig. 7, is likely to be more accurate because a large number of neurons were sampled post lesion (vs. 1 neuron being followed pre- and postacute lesion). A second exception is the presence of LT penile fields after chronic moderate Cx, which damages the dorsal columns (see Table 1; not depicted in Fig. 7).
Functional implications
The MRF is a multifunctional zone, with multiple ascending
and descending inputs and outputs. In general, a nociceptive pathway from the male genitalia ascending via the DLQ to MRF may on one hand be
part of a control mechanism for reflexive reactions to noxious stimuli
(including modulation of ejaculatory reflexes) and/or be a relay for
the ascending control of cortical arousal leading to perceptions of
pain (Jones 1995; Peterson 1979
). Similar studies are now under way in the thalamus, which contains many neurons
responsive to DNP stimulation (Hubscher and Johnson
1998
). A loss of thalamic responses after a bilateral DLQ
lesion would be more indicative of a role in the neural mechanisms that
underlie the perception of noxious stimuli to mucocutaneous and
visceral tissues, such as those that occurs under a variety of
pathological conditions (for example, see review by Wesselmann
et al. 1997
).
Relative to spinal cord injury and its effects on ejaculatory
responses, the presence of DNP-responsive neurons in the MRF, which
contains neurons that project to and modulate the lumbosacral circuits
for ejaculatory responses (Johnson and Hubscher 1998), suggests that these sensory neurons are part of a spino-bulbo-spinal circuit important for proper coordination of perineal muscle
contractions. Bilateral disruption of this ascending sensory pathway in
the midthoracic spinal cord likely contributes to the loss of
ejaculatory ability after chronic spinal cord injury in animals
(Mas et al. 1987
) and humans (Seftel et al.
1991
), although the chronic lesions in the present study also
disrupted the descending projections from MRF to the lumbosacral spinal
cord, which are also contained in the DLQ at the
T8 spinal level (Hubscher and Johnson
1996b
).
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ACKNOWLEDGMENTS |
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We thank V. Dugan and R. Odama for excellent technical assistance. This study was supported by the American Paralysis Association, the Brain and Spinal Cord Rehabilitation Trust Fund of Florida and National Institute of Neurological Disorders and Stroke Grant NS-35702.
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FOOTNOTES |
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Address for reprint requests: C. H. Hubscher, Dept. of Physiological Sciences, University of Florida, Gainesville, FL 32610-0144.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 1 April 1999; accepted in final form 18 May 1999.
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REFERENCES |
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