Bilateral bulbospinal projections to pudendal motoneuron circuitry after chronic spinal cord hemisection injury as revealed by transsynaptic tracing with pseudorabies virus.

Complications of spinal cord injury in males include losing brainstem control of pudendal nerve-innervated perineal muscles involved in erection and ejaculation. We previously described, in adult male rats, a bulbospinal pathway originating in a discrete area within the medullary gigantocellularis (GiA/Gi), and lateral paragigantocellularis (LPGi) nuclei, which when electrically microstimulated unilaterally, produces a bilateral inhibition of pudendal motoneuron reflex circuitry after crossing to the contralateral spinal cord below T8. Microstimulation following a long-term lateral hemisection, however, revealed reflex inhibition from both sides of the medulla, suggesting the development or unmasking of an injury-induced bulbospinal pathway crossing the midline cranial to the spinal lesion. In the present study, we investigated this pathway anatomically using the transsynaptic neuronal tracer pseudorabies virus (PRV) injected unilaterally into the bulbospongiosus muscle in uninjured controls, and ipsilateral to a chronic (1-2 months) unilateral lesion of the lateral funiculus. At 4.75 days post-injection, PRV-labeled cells were found bilaterally in the GiA/Gi/LPGi with equal side-to-side labeling in uninjured controls, and with significantly greater labeling contralateral to the lesion/injection in lesioned animals. The finding of PRV-labeled neurons on both sides of the medulla after removing the mid-thoracic spinal pathway on one side provides anatomical evidence for the bilaterality in both the brainstem origin and the lumbosacral pudendal circuit termination of the spared lateral funicular bulbospinal pathway. This also suggests that this bilaterality may contribute to the quick functional recovery of bladder and sexual functions observed in animals and humans with lateral hemisection injury.

Effects of 17beta-estradiol on responses of viscerosomatic convergent thalamic neurons in the ovariectomized female rat.

Ovarian hormones have been shown to exert multiple effects on CNS function and viscerosomatic convergent activity. Ovariectomized (OVX) female rats were used in the present study to examine the long-term effects of proestrus levels of 17beta-estradiol (EB) delivered by a 60-day time-released subcutaneous pellet on the response properties of viscerosomatic convergent thalamic neurons. In addition, avoidance thresholds to mechanical stimulation for one of the convergent somatic territories, the trunk, was assessed using an electro-von Frey anesthesiometer before and at the end of the 6-wk post-OVX/implant period prior to the terminal electrophysiological experiments, which were done under urethane anesthesia. Rats implanted with an EB-containing pellet, relative to placebo controls, demonstrated 1) altered thalamic response frequencies and thresholds for cervix and vaginal but not colon stimulation; 2) some response variations for just the lateral group of thalamic subnuclei; and 3) altered thalamic response frequencies and thresholds for trunk stimulation. Thalamic response thresholds for trunk pressure in EB versus placebo rats were consistent with the avoidance thresholds obtained from the same groups. In addition, EB replacement affected visceral and somatic thresholds in opposite ways (i.e., reproductive-related structures were less sensitive to pressure, whereas somatic regions showed increased sensitivity). These results have obvious reproductive advantages (i.e., decreased reproductive organ sensitivity for copulation and increased trunk sensitivity for lordosis posturing), as well as possible clinical implications in women suffering from chronic pelvic pain syndromes and/or neuropathic pain.

Effects of surgical induction of endometriosis on response properties of preoptic area neurons in rats.

Subfertility and severe pelvic pains are symptoms associated with endometriosis (ENDO), a common condition among women that is characterized by the growth of the uterine endometrium on the surface of organs within the pelvic region and abdominal cavity. The contribution of the CNS to symptoms associated with ENDO is not known. In the present study, the preoptic area (POA) of the hypothalamus was investigated, as this region of the forebrain is known to play an important role in the neuroendocrine control of the reproductive cycle, mating behavior, and antinociception. Female rats were either induced for ENDO by autotransplantation of uterine tissue (n=20) or uterine fat for surgical sham controls (n=11). Terminal extracellular electrophysiological recordings (urethane anesthesia) were conducted in the POA six weeks post-ENDO induction when the rats were in either the proestrus or metestrus stages of their estrous cycle. Significant differences were found between the ENDO versus SHAM groups of animals for the proportion of inhibitory responses as well as the percentage of neurons responding to stimulation of the abdominal branches of the vagus, which innervates portions of the female reproductive tract, including the ovaries. The endometriotic cysts were found to be significantly larger in proestrus rats (stage when hormones are elevated). These data demonstrate that the responses of POA neurons are influenced by the presence of endometriotic cysts in the abdominal cavity. Since the POA is known to be part of the neural circuitries that mediate nociception and fertility, any deviation from its normal activity under ENDO conditions could contribute to the constellation of symptoms that ensue.

Convergence of nociceptive information in the forebrain of female rats: reproductive organ response variations with stage of estrus.

Neurons in the preoptic area (POA) of the hypothalamus and the bed nucleus of stria terminalis (BST) play an important role in the neuroendocrine control of the reproductive cycle, mating behaviors and nociception. Single unit extracellular recordings were performed in the POA and BST region of 20 urethane anesthetized female rats during either the proestrus (elevated levels of estrogen/progesterone) or metestrus (low circulating hormones) stage of the estrous cycle. A total of 118 neurons in the POA and 65 neurons in the BST responded to the search stimuli, bilateral electrical stimulation of the viscerocutaneous branch of the pelvic nerve and/or sensory branch of the pudendal nerve (i.e., dorsal nerve of clitoris). Most of the neurons responding to the electrical search stimuli received a high degree of somatovisceral convergence, including inputs from the abdominal branches of the vagus, cervix, vagina, colon and skin territories on the perineum and trunk. Mean neuronal response thresholds for vaginal and cervical stimulation but not colon distention were significantly higher for animals tested during proestrus. Also, there was a shift in POA and BST neuronal responsiveness towards more inhibition and less excitation during proestrus for a variety of somatovisceral inputs. These data demonstrate that the changes in hormonal status affect the properties of POA and BST neurons, which likely relates not only to the functional importance of these inputs for reproductive behaviors but also for nociceptive processing as well.