Women with complete spinal cord injury: a phenomenological study of sexual experiences.

This study examines psychosocial, emotional, and relationship aspects of sexuality in the lives of 15 women who sustained complete spinal cord injury (SCI) between the levels of T6 and L2. Phenomenological interviews were organized to chronologically sequence events with the intention of describing the trajectory of sexuality in women with complete SCI. A set of themes emerged from postinjury data that were labeled cognitive-genital dissociation, sexual disenfranchisement, and sexual rediscovery. Broadening the scope of the research beyond the physiological offers insight as to the interplay between the mind and sexual response and guidance for educational and therapeutic interventions.

Naltrexone-induced augmentation of sexual response in men.

BACKGROUND: To ascertain the role of endogenous opioids in sexual response, naltrexone, an opiate receptor antagonist, was administered to men, and its effect on selected self-report measures of sexual response to masturbation was recorded. METHODS: The data are based on results from 20 healthy, sexually active (alone or with a partner) men, aged 20-29 years, who ingested naltrexone (25 mg/day x 3) or placebo in a randomized, double-blind crossover design. There was at least a 14-day interval between drug and placebo treatment. Between 18 and 22 h after the most recent dose of drug or placebo, subjects viewed sexually explicit videos in privacy for 2 h. They were instructed to masturbate and have as many orgasms as desired. The following three different self-report measures of their responses were recorded: number of orgasms; intensity of sexual arousal, and orgasmic intensity. RESULTS: Under the naltrexone condition, the volunteers experienced a significantly greater mean number of orgasms (3.4 +/- 0.2 SEM) than under the placebo condition (2.6 +/- 0.3). The total number of orgasms was 67 under the naltrexone condition and 51 under the placebo condition. At the first orgasm, the measure of intensity of arousal was significantly greater in the naltrexone (3.9 +/- 0.2) than placebo (3.4 +/- 0.2) condition, and the measure of orgasmic intensity was significantly greater in the naltrexone (3.7 +/- 0.2) than in the placebo (3.0 +/- 0.3) condition. CONCLUSIONS: The present study provides evidence that endogenous opioids modulate orgasmic response and the perceived intensity of sexual arousal and orgasm in men. The findings suggest that naltrexone could be clinically useful in cases of inhibited sexual desire and erectile dysfunction.

Evidence that oxytocin is an endogenous stimulator of autonomic sympathetic preganglionics: the pupillary dilatation response to vaginocervical stimulation in the rat.

Vaginocervical mechanostimulation (VS) was shown previously to release oxytocin within the spinal cord and to induce pupillary dilatation. In the present study, (a) injection of oxytocin directly to the spinal cord (10 or 25 microg intrathecally [i.t.] in 5 microl saline) induced pupillary dilatation when observed 1 min after the end of the injection and (b) injection of an oxytocin receptor antagonist ([d(CH2)5-Tyr (Me)2-Orn8]-Vasotocin [OTA]; 25 microg i.t. in 5 microl saline) significantly attenuated the pupillary dilatation response to VS, when VS was applied 3 min after the end of the injection. Since activation of autonomic sympathetic preganglionic neurons in the thoracic spinal cord produces pupillary dilatation, we propose that oxytocin is a central nervous system neurotransmitter that stimulates these neurons directly, or perhaps indirectly, and thus is a mediator of VS-produced pupillary dilatation.

Combined c-fos and 14C-2-deoxyglucose method to differentiate site-specific excitation from disinhibition: analysis of maternal behavior in the rat.

On the basis of evidence that 14C-2-deoxyglucose (2-DG) autoradiography indicates activity at axonal terminals, whereas c-fos immunocytochemistry indicates activity of neuronal cell bodies, we combined these techniques in adjacent histological brain sections to assess excitatory and disinhibitory synaptic relations in selected sites in female rats in which maternal behavior was elicited by natural parturition, sensitization (7- to 10-day cohabitation with foster pups), or hysterectomy. All individuals in these three groups expressed maternal behavior immediately before 2-DG injection. Controls were non-maternal virgins. Parturient and Hysterectomized groups: elevation (compared with controls) in both 2-DG and c-fos activity in medial preoptic area (MPOA) indicated an increase in its input and output activity, i.e., an excitatory interaction; the MPOA was previously shown to be critical for maternal behavior. Sensitized group: a decrease in 2-DG activity of vomeronasal nuclei (bed nucleus of the accessory olfactory tract, BAOT, and medial amygdala, ME, replicating our previous study) and an elevation in c-fos activity, jointly indicate disinhibition of these nuclei, that were previously shown to modulate pup-chemostimulation-induced sensitization. All other sites showed evidence of excitatory input-output relationships (i.e., joint increase in both 2-DG and c-fos activity), e.g., bed nucleus of the stria terminalis (BNST), lateral habenula (LHAB), central gray (CG), thalamus (THAL), septum (SEPT), and ventral tegmental area (VTA). The present study demonstrates the feasibility of measuring 2-DG and c-fos activity jointly in adjacent sections of the same brain, thereby providing evidence to distinguish between localized excitation and disinhibition.

Analgesic synergism between AP5 (an NMDA receptor antagonist) and vaginocervical stimulation in the rat.

Vaginocervical stimulation (VS) releases multiple neurotransmitters into superfusates of the spinal cord; these can stimulate both nociceptive (e.g., glutamate, and glycine acting at the NMDA site), and antinociceptive (e.g., GABA, norepinephrine, 5-HT, and glycine acting at the strychnine-sensitive receptor) systems. Although the balance between these two opposing systems can determine the nature, magnitude, and duration of the response to VS, the characteristic prevailing response to VS is analgesia. We hypothesized that by counteracting the nociceptive component of this system, the magnitude and duration of the response to VS would be augmented. In the present study, the NMDA receptor antagonist AP5 [10 microg injected intrathecally (i.t.)] significantly increased the magnitude and duration of the analgesia (measured as tail flick latency to radiant heat) produced by VS (200 g force). At several time points the analgesic effect of AP5 combined with VS was greater than the sum of the effects of AP5 and VS separately, suggesting that they act synergistically. We propose that AP5 potentiates the analgesic effect of VS by two mechanisms: (a) antagonizing the putative pain-producing action of glutamate and glycine acting jointly at the NMDA receptor, and consequently, (b) permitting the unimpeded expression of the analgesic action of inhibitory neurotransmitters released by VS (e.g., glycine at the strychnine-sensitive receptor, and GABA).

Love as sensory stimulation: physiological consequences of its deprivation and expression.

For the present purpose, love is defined as one's having stimulation that one desires. The nature of the stimulation can range on a continuum from the most abstract cognitive, to the most direct sensory, forms. Thus, this definition of love encompasses having an emotional bond with a person for whom one yearns, as well as having sensory stimulation that one desires. We address some of the physiological and perceptual consequences both of having, and of not having, love. We propose a neural mechanism by which deprivation of love may generate endogenous, compensatory sensory stimulation that manifests itself as psychosomatic illness. In addition, we propose a neuroendocrine mechanism underlying sexual response and orgasm. The latter includes vaginocervical sensory pathways to the brain that can produce analgesia, release oxytocin, and/or bypass the spinal cord via the vagus nerve. We present evidence of the existence of non-genital orgasms, which suggests that genital orgasm is a special case of a more pervasive orgasmic process. Through recent studies, the mechanisms and manifestations of love and its deprivation are becoming better understood. The better is our understanding of love, the greater is our respect for the significance and potency of its role in mental and physical health.

'Complete' spinal cord injury does not block perceptual responses to genital self-stimulation in women.

BACKGROUND: A priori hypothesis: vaginal and/or cervical self-stimulation will not produce perceptual responses in women with "complete" spinal cord injury (SCI) at or above the highest level of entry of the hypogastric nerves (T10-12) but will produce perceptual responses if SCI is below T-10. DESIGN: Women with complete SCI were assigned to a group with "upper" (T-10 and/or above) (n = 6) or "lower" (below T-10) (n = 10) SCI; uninjured women (n = 5) constituted a control group. Perceptual response to vaginal and/or cervical self-stimulation was quantified as magnitude of analgesia to calibrated finger compressive force. SETTING: Rutgers, The State University of New Jersey, Human Physiology Laboratory, College of Nursing, Newark. PARTICIPANTS: Consecutive samples of first 16 of 34 women with SCI who responded to nationwide advertisements, met inclusion criteria, and volunteered; control group was the first 5 respondents. INTERVENTION: Vaginal or cervical (cervix uteri) self-stimulation applied for 12 minutes, interspersed with non-stimulation periods, while measuring analgesia. MAIN OUTCOME MEASURE: Quantify analgesia magnitude to vaginal or cervical self-stimulation. RESULTS: Significant analgesia was produced in the uninjured group and the group with lower SCI, supporting the hypothesis. Unexpectedly, significant analgesia was also produced in the group with upper SCI. Women in the group with upper SCI also experienced menstrual discomfort, awareness of vaginal and/or cervical stimulation per se, and orgasms. CONCLUSIONS: (1) Genitospinal visceral afferent pathways function in the women in the group with upper SCI, although unrecognized by the American Spinal Injury Association criteria, and/or (2) there exists a functional genital afferent pathway that bypasses the spinal cord and projects directly to the brain, which we propose to be via the vagus nerves.

Cardiovascular responses to vaginocervical stimulation in the spinal cord-transected rat.

The present study ascertained whether increases in heart rate (HR) and systolic blood pressure (SBP) produced by vaginocervical stimulation (VS; 500 g force) persist in the unanesthetized rat after chronic spinal cord transection at selected levels. Three groups were used: spinal cord transection at T7 (n = 10) or L5 (n = 10) or a sham-operated control group (Sh, n = 10). In the Sh group, VS increased significantly both HR, by 95 +/- 14.3 beats/min (bpm) (22 +/- 3.7% above baseline), and BP, by 37 +/- 5.7 mmHg (37 +/- 7.7% above baseline), confirming earlier findings. In the T7 group, VS significantly decreased HR by 107 +/- 21.4 bpm (27 +/- 4.1% below baseline) and increased BP by 41.3 +/- 12.9 mmHg (32 +/- 8.3% above baseline). In response to VS, HR increased in every rat in the Sh group and decreased in every rat in the T7 group. In the L5 group, VS failed to significantly affect HR or BP. In the present study, specific levels of spinal cord transection produced differential HR and BP responses to VS in the rat. A model is presented addressing the component responses of autonomic dysreflexia that can occur, contingent on the level of spinal cord injury, in women during parturition or sexual intercourse.

Solution structure of vasoactive intestinal polypeptide (11-28)-NH2, a fragment with analgesic properties.

An 18-residue-long fragment of vasoactive intestinal polypeptide [VIP(11-28)-NH2] that is known to be analgesic was synthesized by solid-phase t-Boc methodology on a 4-methylbenzhydrylamine resin. Circular dichroism spectroscopy gave evidence that the peptid acquires about 60% helical structure in 50/50 methanol/phosphate buffer, pH 6.0, and 65% (+/-5%) helicity in 80/20 methanol/phosphate buffer pH 7.0, A 2.0 mM solution of VIP (11-28) NH2 in 80% methanol, 20% phosphate buffer pH 7.0 was subjected to 2-dimensional nuclear magnetic resonance (NMR) studies The NMR results suggested formation of an extended helical structure extending from residue 11 to 27 essentially the same region found to be helical in a VIP(1-28)-NH2 and log. This finding suggests that the sequence required for analgesia assumes a helical structure at the receptor.

Antinociceptive action of vaginocervical stimulation in rat spinal cord: 2-DG analysis.

Using [14C] 2-deoxyglucose (2-DG) autoradiography with computerized densitometric analysis, unilateral foot pinch was found to significantly increase the relative optical density in laminae I and II of the ipsilateral, compared to the contralateral, spinal cord at lumbar 5 (L5). However, during vaginocervical mechanostimulation applied concurrently with the unilateral foot pinch, no comparable difference was observed. No response to foot pinch was observed in other laminae of the spinal cord at L5, and no effects comparable to the above were observed at L3. These findings indicate that vaginocervical mechanostimulation suppresses neural responses to noxious foot pinch stimulation selectively at the laminae I and II level of the spinal cord at L5, but not at L3.

Vagotomy blocks responses to vaginocervical stimulation after genitospinal neurectomy in rats.

To ascertain whether any effects of vaginocervical stimulation (VS) are mediated by the vagus nerve, all known afferent nerves from the reproductive tract to the spinal cord were transected and the rats were tested for residual responses to VS. After combined bilateral transection of the pelvic, hypogastric, and pudendal nerves (NX), the following responses to VS were greatly reduced or abolished: lordosis to flank-perineum palpation, leg extension, immobilization, and blockage of both tail withdrawal to radiant heat and leg withdrawal to foot pinch. However, after these nerve cuts, the following persisted as significant residual responses to VS: 1) analgesia [measured as increase in vocalization threshold (VOCT) to tailshock], 2) pupil dilatation (PD), and 3) increase in heart rate (HR). Subsequent bilateral subdiaphragmatic vagotomy (VX) significantly reduced the magnitude of PD and abolished the analgesia. By contrast, VX produced no significant effect on the HR increase to VS. The above findings provide evidence that brain-mediated responses to vaginocervical stimulation can be elicited via the vagus nerves.

Brain-mediated responses to vaginocervical stimulation in spinal cord-transected rats: role of the vagus nerves.

The present study was designed to ascertain whether the vagus nerves convey functional sensory activity from the reproductive tract in rats. Previously, vaginocervical mechanostimulation (VS) was shown to increase pupil diameter (PD) and the threshold of vocalization to tail shock (Voc-T). These responses were attenuated but not abolished by combined bilateral transection of the 'genito-spinal' nerves (i.e. pelvic, hypogastric and pudendal). Subsequent bilateral vagotomy further reduced or abolished the residual responses. In the present study, spinal cord transection above the known level of entry of the genito-spinal nerves was combined with bilateral vagotomy. In ovariectomized rats, after spinal cord transection at thoracic 7 (T7X), lumbar 5 (L5X) levels, or sham surgery (Sh), responses to VS were measured, the vagus nerves were then transected bilaterally, and responses to VS were again measured. VS significantly increased Voc-T and PD after sham procedure or spinal cord transection at either level. Subsequent bilateral vagotomy abolished the VS-induced increase in PD in the T7X group. Due to low survival rate, the effect of vagotomy on Voc-T could not be determined. Consequently, we performed a second experiment. In non-ovariectomized rats, VS significantly increased PD but reduced Voc-T in the T7X group compared to the Sh group, and subsequent bilateral vagotomy abolished both responses. These findings provide evidence that, in the rat, the vagus nerves provide a functional sensory pathway from the reproductive tract directly to the medulla oblongata of the brain, bypassing the spinal cord.

Brain 2-deoxyglucose levels related to maternal behavior-inducing stimuli in the rat.

Levels of [14C]2-deoxyglucose (2-DG), measured autoradiographically, in the medial preoptic area (MPOA), were higher during natural parturition with concurrent maternal behavior than in non-pregnant non-maternal controls, whereas levels in the vomeronasal system were lower in virgin rats made maternal by cohabitation with young than in control and parturient rats. Previous studies have shown that lesions of MPOA disrupt maternal behavior, whereas lesions of vomeronasal structures stimulate it, and that an increase in 2-DG levels is indicative of an increase in firing activity in neuron terminals. Consequently, the present findings suggest that maternal behavior can be induced by: (a) an increase in parturition-generated sensory stimulatory input to the MPOA in response to mechanostimulation of the birth canal, and (b) a separate chemosensory vomeronasal pathway whose activity is reduced cohabitation with young, thereby disinhibiting maternal behavior.

Inhibition of withdrawal responses by pelvic nerve electrical stimulation.

In urethane-anesthetized rats, the compound action potential of the pelvic nerve was found to consist of three different waves, two in the A delta fiber and one in the C-fiber range of conduction velocity. Electrical stimulation of the pelvic nerve produced a complete inhibition of the withdrawal response to noxious foot pinch or foot compression. The electromyographic (EMG) activity of the contralateral posterior biceps muscle was used to record the withdrawal response. The withdrawal response inhibition was related to the duration and the frequency of electrical stimulation. Low (5-10 Hz) and high (100-300 Hz) frequencies were ineffective in inhibiting the withdrawal response, whereas intermediate frequencies (20-80 Hz) produced a complete inhibition of the withdrawal response. Short (300 ms) trains of stimulation inhibited the withdrawal response only during the stimulation period. Longer trains of stimulation (500 ms-10 s) produced long-lasting inhibition of the response to noxious stimulation. The inhibition persisted for up to 20 s after the end of electrical stimulation of the pelvic nerve. A delta fiber stimulation was adequate to inhibit the withdrawal response in most (15 out of 17) of the animals. However, A delta plus C-fiber stimulation was needed to inhibit the response to noxious stimulation in two animals. In addition to inhibiting the response to noxious stimulation, pelvic nerve electrical stimulation reflexively activated abdominal muscles. On the basis of present findings using electrical stimulation, it can be suggested that, in the rat, A delta and C-visceral afferents of the pelvic nerve mediate the analgesic effect of vaginocervical probing pelvic and A delta afferents the contraction of abdominal muscles in the fetus-expulsion reflex.

Pelvic neurectomy blocks oxytocin-facilitated sexual receptivity in rats.

The effect of bilateral pelvic, hypogastric, or pudendal neurectomy on oxytocin-induced facilitation of lordosis behavior was examined in ovariectomized, estrogen, and progesterone primed female rats. Oxytocin-induced facilitation of lordosis behavior was significantly decreased following bilateral pelvic, or combined bilateral pelvic and hypogastric neurectomy. Hypogastric only or pudendal only neurectomy had no effect on the facilitation of lordosis behavior after systemic administration of oxytocin. These results suggest that the integrity of the pelvic nerve is necessary and sufficient to mediate the stimulatory effects of systemically administered oxytocin on receptivity.

Momentary analgesia produced by copulation in female rats.

To assess possible changes in nociception during copulation in estrous rats, electric shocks that were 20% suprathreshold for eliciting vocalization in response to tail shock (STS), were applied to the tail before the initiation of copulation and, thereafter, coincident with the onset of mounting bouts by the male (Experiment 1). Females vocalized significantly less during non-intromittive mounts (M; P < 0.001), intromissions (I; P < 0.001), and ejaculation (E; P < 0.01) than before the initiation of copulation. In order to assess the importance of vaginal stimulation (VS) by penile insertion during mating, in Experiment 2 30% STS were applied 300-400 ms after the initiation of mounting to ensure that the stimuli fell within the period of penile insertion occurring during I and E. M failed to significantly inhibit vocalizations to 30% STS. By contrast, both I and E markedly inhibited vocalizations in response to STS. This effect was transitory since subjects (Ss) vocalized to nearly all 30% STS when delivered 15 s after I or E. Copulatory analgesia (CA) was abolished by the bilateral transection of the pelvic and hypogastric nerves but not by the transection of the pudendal nerve (Experiment 3). The magnitude of CA was calibrated by determining the doses of morphine sulfate (MS) required to produce similar decrements in vocalization to STS. The analgesic effects of I and E were equivalent to more than 10 mg/kg and 15 mg/kg, respectively, of MS (Experiment 4). Pelvic-hypogastric neurectomy, but not pudendal neurectomy, also significantly reduced the effect of VS on facilitating lordosis, inducing immobilization and hind leg extension, and blocking the withdrawal reflex to foot pinch (Experiment 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Vaginocervical stimulation attenuates hindpaw shock-induced substance P release into spinal cord superfusates in rats.

The present study was designed to elucidate the mechanism in the spinal cord by which vaginocervical stimulation (VS) attenuates responses to noxious stimulation. This was accomplished by testing the hypothesis that VS reduces noxious stimulation-induced release of substance P at the level of the spinal cord. Noxious foot shock significantly increased the release of substance P (measured using radioimmunoassay) into superfusates of the lumbosacral spinal cord region in urethane-anesthetized rats. VS applied concurrently with foot shock significantly attenuated the release of substance P compared to the foot shock-only condition. In addition, substance P levels were significantly lower after the VS-only condition than after the no stimulation or foot shock-only conditions. These findings indicate that VS may produce analgesia, at least in part, by suppressing the release of substance P within the spinal cord.

Release of amino acids into regional superfusates of the spinal cord by mechano-stimulation of the reproductive tract.

Based on pharmacological evidence that inhibitory amino acids mediate vaginocervical mechano-stimulation produced analgesia (VSPA), we hypothesized that inhibitory amino acids would be released endogenously in the spinal cord in response to vaginocervical mechano-stimulation (VS). This hypothesis was tested by HPLC analysis of the amino acid content of 5-min superfusates of the spinal cord before, during and after VS (400 g force applied against the cervix) in urethane-anesthetized rats. Utilizing an in vivo push-pull superfusion method, artificial cerebrospinal fluid was continuously superfused over the spinal cord through the intrathecal space surrounding the sacral-lower thoracic region. In addition, concentrations of amino acids in the superfusate were measured in response to KCl stimulation (increasing the superfusion medium from 3.4 to 40.0 mM KCl to produce non-specific depolarization), and noxious hind paw mechano-stimulation (pinching the hind paw to produce a sustained flexor response in ipsilateral hind leg). There was a significant increase in the concentration of Gly, Tau, Asp, Glu and Lys in the superfusate in response to VS (n = 8) and to KCl (n = 8), but not to hind paw stimulation (n = 5). Also, GABA concentrations increased in response to KCl, and the concentration of Ala, Ser, Gln, Thr, Arg and Phe increased in response to VS, however, GABA levels were sometimes below the limits of detection. In contrast, there was no significant change in any amino acid concentration in response to hind paw pinch stimulation, and VS did not significantly affect the concentrations of Tyr, His, Ile, Leu, Met, Trp or Val. The present findings support our hypothesis that VS releases inhibitory amino acids in the spinal cord. Moreover, other amino acids, including 'excitatory' amino acids, are released into the superfusate. The profile of amino acid release in response to VS differs from that in response to paw pinch or KCl administration.

Expression of c-fos protein in lumbosacral spinal cord in response to vaginocervical stimulation in rats.

The pattern of vaginocervical stimulation-evoked expression of the proto-oncogene c-fos in lumbar 5-sacral 1 segments of the spinal cord of ovariectomized adult rats was mapped using immunocytochemistry. A calibrated force of mechanostimulation was applied to the vaginal cervix of experimental animals and to the perineum of control animals while they were gently restrained. The number of cells expressing c-fos was significantly greater in the experimental than the control animals in laminae I, IV, V-VI and X. The implications of the present findings for elucidating the spinal pathways mediating the various behavioral, neuroendocrine and autonomic effects of vaginocervical stimulation (VS) are discussed.