ELSEVIER Brain Research 656 (1994) 52-58

BRAIN RESEARCH

Research report

Momentary analgesia produced by copulation in female rats

P. Gdmora a, C. Beyer a,,, G. Gonzfilez-Mariscal a, B.R. Komisaruk b '~ Centro de Im,estigaci6n en Reproduccidn Animal, CINVESTA V-Unit'ersidad Aut6noma de Tlaxcala, Apartado Postal 62,

Tlaxcala, Tlax. 90,000, Mexico ~' Institute of Animal Behauior, Rutgers Unil,ersity, 101 Warren St., Newark, NJ 07102. USA

Accepted 24 May 1994

Abstract

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-intromit- tive 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 ocurring 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 l 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 ! 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). Pelvic-hypogastric neurectomy also significantly reduced sexual receptivity, as indicated by a reduction in the number of I that the females in this group received.

Key words: Nociception; Pain; Analgesia; Copulation; Female sexual behavior; Pelvic nerve; Pudendal nerve; Hypogastric nerve; Mount; Intromission; Ejaculation

1. Introduction

The analgesia produced by vaginocervical mechano- st imulation in the rat has been analyzed from neu- roanatomical [4], neurophysiological [13], pharmacolog- ical [9,18,19,23], and behavioral [13] perspectives [14]. However, l ittle is known regarding the natural counter- part, if any, of this form of analgesia. It has been reported that vaginal self-st imulation in women in- duces analgesia [26], and anecdotal reports suggest that sexual activity attenuates pain percept ion in women. Nonetheless, no systematic study on the possible ef- fects of female copulat ion on nociception has yet been made. Therefore, in the present study we explored in female rats whether the vaginal st imulation produced

* Corresponding author. Fax: (52) (246) 23164.

0006-8993/94/$07.00 1994 Elsevier Science B.V. All rights reserved SSDI 0006-8993(94)00657-X

by the intromissions (I) and ejaculation (E) occurring during copulat ion induces analgesia. The possible role of afferent activity coming from the vagino-cervical region in the product ion of copulatory analgesia (CA) was then tested by selective neurectomies. Finally, the relative magnitude of CA was assessed by comparing it against a dose- response curve of morphine sulfate (MS).

2. Materials and methods

2.1. Experiment 1: Determination qf CA in female rats

2.1.1. Animals Subjects (Ss) were adult Wistar female rats (200-250 g b.wt.).

They were maintained in a reversed 14 h light:10 h dark cycle (lights off at 12.00 h) at a temperature of 23-24C. They were provided with

P. Gdmora et al. /Brain Research 656 (1994) 52-58 53

rat pellets (Purina) and water ad libitum. Four Ss were housed/cage. They were bilaterally ovariectomized (ovx) under ether anesthesia and given an i.m. injection of 100,000 IU penicillin after the opera- tion. Three weeks later Ss were injected s.c. with: 10 /xg estradiol benzoate (EB; Sigma, St. Louis, MO; in 0.1 ml sesame oil), followed by 5 p.g EB 24 h later and 2 mg progesterone (P; Sigma; in 0.1 ml sesame oil) 24 h after the last EB injection. Sexual receptivity was tested 4 h after P by placing females inside a round (50 cm diameter) Plexiglas arena together with a vigorous, sexually experienced male. Females received ten mounts by the male and only those showing a lordosis quotient [LQ = (number of lordosis/number of mounts)x 100] of at least 80 were used in this experiment. All observations were performed during the dark phase of the cycle under dim red light illumination.

2.1.2. Measurement of vocalization threshold A sexually receptive female was placed inside a round Plexiglas

arena (50 cm diameter) and was allowed to adapt for 5 min. A pair of electrodes was then attached to the tail and connected to a DC stimulator (Coulbourn Model E 13-51) via a rotatory connector, as described previously [8]. The characteristics of the stimuli were: 1 ms pulses, 50 Hz, 300 ms train duration. Vocalization threshold to tail shock (VTTS) was determined by increasing the current in steps of 0.1 mA until the rat vocalized and then decreasing the current in steps of 0.1 mA until vocalization ceased. This process was repeated three times and the six inflection points thus obtained were averaged to provide an estimate of VTTS.

2.1.3. Protocol 1 This study investigated if nociception was modified in receptive

females (n = 22) while they were mounted by the male. Before copulation ten shocks of 20% intensity above threshold (suprathreshold shocks, STS) were delivered at 10-s intervals and the number of vocalizations thus elicited was recorded. A vigorous, sexually experienced male rat was then introduced into the arena and allowed to copulate with the female. A single 20% STS was given to females at the onset of each mounting train. These were classified as: non-intromittive (M), I or E depending on their well- established motor characteristics. The percentage of STS that elicited vocalization following M or I across the whole copulatory series was calculated post hoc for each animal, and the percentage of Ss vocalizing after a single E (n = 11) was also determined. Thus, the timing of shocking and the total number of shocks each female received was determined by the male's behavior, rather than by a predetermined schedule since the experimenter delivered each shock upon initiation of the mounting train. Thus, the experimenter did not know if the mounting train would result in a M, an I or an E. With this stimulation schedule electric shocks fell between 100-150 ms after initiation of the event. Sexually unreceptive females (ovx and treated only with oil; n= 10) were also used and tested as the sexually receptive Ss to determine if mounting trains elicited analge- sia in anestrous females.

isons. The effect of a single E on nociception was determined by comparing the occurrence of vocalization to the last STS delivered BC with that observed immediately after E. A sign test was used for this comparison [21].

2.2. Experiment 2: Effect of vaginocervical stimulation during intromis- sions and ejaculation on CA in female rats

2.2.1. Animals Adult Wistar female rats (200-250 g b.wt.), housed as described

above, were ovariectomized under ketamine (70 mg/kg)+rompun (0.1 mg/kg) anesthesia. Two weeks later they received EB (10 /xg/day) for 4-5 days until they showed an LQ of at least 60. Progesterone was not administered in this experiment.

This experiment was performed to ascertain the importance of vaginal stimulation (VS) by penile insertion during copulation for inducing CA. Stimuli of higher intensity than in Experiment 1 (30% above baseline) were used to have a control condition in which electric shocks (10 shocks delivered 10 s apart) induced above 95% of vocalizations (before initiating copulation) and to ascertain whether a greater difference between the effects of I vs. E would become evident. Sexually receptive females (n = 18) were introduced into a round Plexiglas arena and allowed to adapt for 5 min, as described above. Polygraphic analysis of the motor copulatory pattern in the male rat has shown that the average duration of the I pattern is 314 ms and that penile insertion, which occurs between 200-250 ms after the initiation of thrusting, lasts an average of 410 ms [1,16]. On the other hand, penile insertion during the E pattern usually occurs between 200-400 ms after the initiation of thrusting and lasts for over 1 s [1,16]. Therefore, to insure that shocks coincided with VS (i.e. with penile insertion), a delay (300-400 ms) was introduced between the initiation of the behavioral events and the shocking. The percentage of shocks that elicited vocalizations during M and I in a copulatory series was established and the percentage of Ss vocalizing during E was also determined. The number of M and I each female received across the copulatory series as well as the occurrence of lordosis in response to these events was also determined. In order to control for spontaneous fluctuations in nociception a STS was deliv- ered 15 s after the occurrence of the behavioral event and its corresponding shock.

2.2.2. Statistical analysis The effect of M and I on nociception was assessed by comparing

the proportion of 30% STS that elicited vocalization BC vs. the proportion observed when females were receiving I from the male. A paired t-test was used for these comparisons. The effect of E on nociception was assessed by comparing the percentage of Ss that vocalized to the last STS delivered BC vs. the proportion of Ss responding to the shock delivered during E. A sign test was used for these comparisons [21]. Similar comparisons were made between the values obtained during I and E and those obtained after shocks were delivered 15 s later.

2.1.4. Protocol 2 This study tried to determine if the analgesia induced by M, I or

E out-lasted the performance of these events. Thus, in an independ- ent group of animals (n = 8) a single 20% STS was delivered 10 s after each M, I or E across the whole copulatory series and the occurrence of vocalizations was determined as in Protocol 1 (section 2.1.3).

2.1.5. Statistical analysis The effect of M and I on nociception was assessed by comparing

the proportion of 20% STS that elicited vocalization before copula- tion (BC) vs. the proportion observed when females were receiving M or I from the male. A paired t-test was used for these compar-

2.3. Experiment 3: Effect of selective neurectomies on CA

This study explored the effect of transecting the pelvic and hypogastric or the pudendal nerves on the occurrence of CA. All 18 Ss tested in Experiment 2 underwent surgery, under ketamine/ rompun anesthesia, as follows: (1) Pelvic-hypogastric neurectomy (n = 6): a 5 cm midline incision was made and the hypogastric nerves were visualized at the site in the mesentery where they diverge toward the midline from the ureters, near the site where the ureters pass dorsal to the uterine horns. A 1 cm segment of the nerve was removed bilaterally. The pelvic nerve of each side was then visualized by locating the site at which it crosses over the internal iliac vein. Using a fine hook, the

54 P. G6mora et al. /Brain Research 656 (1994) 52-58

pelvic nerve on each side was lifted away from the vein and a 0.5 cm segment was cut away. The abdominal muscle was then sutured and wound clips closed the abdominal skin incision. (2) Pudendal neurectomy (n = 6): following the midline incision the pudendal nerve was visualized dorsal to the pelvic nerve at the site where it crosses over the internal iliac vein. A 0.5 cm segment of the nerve on each side was then removed and the abdominal muscle and skin were sutured as above. (3) Sham neurectomy (n = 6): all three nerves (pelvic, hypogastric and pudendal) were visualized as in the previous groups but were not cut. The abdominal muscle and skin were sutured as above. One week after surgery all females received EB as in Experiment 2 to induce sexual receptivity. Nociception was assessed across the copu- latory series by using the same experimental paradigm described in Experiment 2. The number of M and I each female received across the copulatory series as well as the occurrence of lordosis in response to these events was also determined.

2.3.1. Statistical analysis The effect of I and E on nociception and the impact of selective

neurectomies was assessed as in Experiment 2.

2.4. Experiment 4: Comparison of the magnitude of CA against mor- phine-induced analgesia

2.4.1. Animals All 18 Ss used in the previous experiment continued receiving the

daily estrogen treatment and were tested 1 week after the end of Experiment 3.

The incidence of vocalizations to ten 30% STS (delivered 10 s apart) was determined immediately before and 30 min after injecting morphine sulfate (MS; Sigma; i.p. in 0.07-0.25 ml of saline) at one of the following doses: 0, 5, 10 or 15 mg/kg. These four groups included animals from the three neurectomized groups of Experi- ment 3. 24-48 h later the experiment was repeated with the same animals but allotting them, at random, to different groups. No female received the same dose of morphine twice. Final data were obtained from eight animals in each dose of MS.

2. 4.2. Statistical analysis The analgesic effect provoked by the different doses of MS was

assessed by comparing the proportion of 30% STS that elicited vocalization in the control group (0 mg/kg MS) and in each of the groups that received a particular dose of MS. A t-test for two independent means was used for these comparisons.

2.5. Experiment 5." Effect of neurectomies on the occurrence of uaginocervical-stimulated reflexes

2.5. l. Animals All 18 Ss used in the previous experiment continued receiving the

daily estrogen treatment to maintain their sexual receptivity and were tested 1 week after the end of Experiment 4.

All females received artificial vaginocervical stimulation with a glass rod as described previously [10,13] and the occurrence of the following reflexes was assessed: immobilization, hind leg extension, blockage of the withdrawal to foot pinch and intensity of lordosis (rated on a scale of 0 to 4 as described by Komisaruk and Diakow [11]).

2.5.2. Statistical analysis A sign test [21] was used to assess the effect of neurectomies on

the incidence of sexual reflexes. A t-test for two independent means was used to compare the differences in the intensity of lordosis between sham-operated and neurectomized groups.

3. Resu l t s

3.1. Experiment 1

Fig. 1 shows that the application of 20% STS to receptive females (primed with EB + P) before copula- tion-induced vocalization in 73 _+3% of the cases (mean +_ S.E.M.). Vocalization was reduced to 30 +_ 6% and 9 _+ 4% (P < 0.001) when shocks were given at the onset of M and I, respectively. I were significantly more effective than M for inducing analgesia (P < 0.01). E did not provoke a stronger analgesic effect than I, 9% of Ss vocalizing to the single STS applied during E (P < 0.01). The proportion of vocalizations increased to 55 _+ 6% responses when shocks were given 10 s after these events. This reduction in vocalization was not statistically different from precopulatory values. Anestrous Ss (ovx rats given only oil) failed to display lordosis and showed no difference in the percentage of vocalizations before copulation and during M (data not shown).

3.2. Experiment 2

Fig. 2 shows that females made receptive with re- peated injections of EB and given 30% STS vocalized in nearly all cases (99%) before copulation. A signifi- cant (P < 0.02) reduction in vocalization was observed when STS were delivered during the intromittive phases of I (21% of STS) and E (23% of STS). By contrast, no inhibition of vocalization was noted when shocks were administered during M (86% _+ 4%) or 15 s after the occurrence of I (99 + 2%) or E (98 _+ 3%).

lOO

90

~ 80

~ 70 o 60

z 50 o ~ 40 N ~ 30 <

U o 20

o

&

T 22 22 I 22 I

i i i

BC M I

Fig. 1. Effects of mating on nociception in ovariectomized (ovx), sexually receptive rats primed with estradiol benzoate + progesterone. The percent of vocalizations to 20% suprathreshold shocks (STS) applied to the tail was determined before copulation (BC; 10 shocks, 10 s apart) and while females were receiving mounts (M) or intromis- sions (I) from the male (one shock/event). Data show means plus standard error. Numbers in bars indicate number of subjects in the corresponding condition, e, p < 0.001 vs. value BC.

P. G6mora et al. / Brain Research 656 (1994) 52-58 55

100

01 1--

8O tR 0 1,3

0 ~- 60 O3 Z 0 ~- 40 20,

lO

0 EJACULATION

0 ; ,0

MORPHINE SULFATE (mg/Kg)

Fig. 4. Comparison of the magnitude of copulatory analgesia with that induced by morphine sulfate (MS). The percent of vocalizations to 30% suprathreshold shocks (STS) was determined, in the same animals appearing in Figs. 2 and 3, 30 min after the i.p. injection of MS: bold line (mean+S.E.M.). Superimposed on this line are the mean nociception values of all animals in Fig. 2 before copulation, while receiving I and immediately after E. * P < 0.05; *** P < 0.005 vs. 0 mg/kg MS.

3.3. Experiment 3

Fig. 3 shows the effect of selective neurectomies on CA. The analgesic effect provoked by I and E in sham-operated Ss was also observed in animals that underwent pudendal neurectomy but not in those sub- jected to pelvic-hypogastric neurectomy. Thus, while vocalization occurred in only 26 10% and 18 7% of cases after I in sham-operated and pudendal neurec- tomized Ss, respectively, animals subjected to pelvic-

100

m 80

~ so 7

o 40 &

N

N 2o

0 BC I E

[ ISHAM ~PUDENDAL NEURECTOMY

~PELVIC+HYPOGASTRIC NEURECTOMY

Fig. 3. Effect of selective neurectomies on copulatory analgesia (CA). Nociception was assessed as in Fig. 2 1 week after females had undergone sham-surgery (n = 6), pudendal neurectomy (n = 6) or pelvic + hypogastric neurectomy (n = 6). Note that pelvic + hypogastric neurectomy abolished CA. Data show means plus stand- ard error. * P < 0.05; ** P < 0.002; & P < 0.001 vs. value BC.

hypogastric neurectomy vocalized in 92 5% of cases. The corresponding figures observed during E were 0% and 0% vs. 100%. As in intact Ss the analgesic effects of I and E were transitory, since they were observed only during, but not 15 s after, these events in sham- operated and in pudendal-neurectomized animals (data not shown).

3.4. Experiment 4

Fig. 4 shows the magnitude of the analgesia induced by the i.p. injection of morphine sulfate (MS) as a function of dose. The percent vocalizations observed after applying 30% suprathreshold shocks to ovx EB- primed females injected with 0, 5, 10 or 15 mg/kg MS were 90 ___ 6, 69 + 15, 42 + 14 and 15 + 12, respectively. By comparison, the magnitude of the analgesia induced by I was similar to that produced by the dose of 15 mg/kg MS and E induced a more intense analgesia than that provoked by this dose of MS.

3.5. Experiment 5

Fig. 5 shows that vaginocervical stimulation (VCS) elicited, in all sham-operated and pudendal neurec- tomized Ss, immobilization, hindlimb extension and blockage of leg withdrawal after foot pinch. By con- trast, in the group subjected to pelvic-hypogastric neurectomy, the percent of Ss showing these responses was reduced to 40, 20 and 0% (P < 0.05), respectively. Fig. 6 shows that the intensity of the lordosis induced by flank palpation combined with VCS was signifi- cantly reduced in the pelvic-hypogastric neurectomized group (P < 0.05).

56 P. G6mora et al. / Brain Research 656 (1994) 52-58

1 O0

80

60

40

20

IMMOBILITY

(3 Z

Z 0 Q.

n~

m

i

HINDLIMB EXTENSION

m

BLOCKAGE OF LEG WITHDRAWAL

Fig. 5. The percent of subjects (Ss) that showed immobility, hindlimb extension and blockage of leg withdrawal was determined in estrogen primed sham-operated (open bars), pudendal neurectomized (hatched bars) and pelvic + hypogastric neurectomized (cross-hatched bars) rats after vaginocervical stimulation. * P < 0.05 vs. sham-oper- ated group.

Pelvic-hypogastric neurectomy also modified some aspects of female sexual behavior. Ss received a signifi- cantly lower number of I after neurectomy than before the operation (4.8 + 0.9 vs. 10.5 _+ 1.5; P < 0.05). By contrast, no significant change in the number of I received was observed in sham-operated Ss (8.8 _+ 1.2 vs. 9.7_+ 2.6) nor in those that underwent pudendal neurectomy (7.7 + 1.2 vs. 8.7 2.8). None of the surgi- cal procedures significantly modified the number of M that females received across the copulatory series (data not shown). The lordosis quotient observed before and after neurectomies was also unmodified in all three groups (sham group, 66_+ 7 vs. 59 7; pudendal neurectomy group, 60 +_ 7 vs. 56 _+ 4; pelvic-hypogastric

3.5

3 .0

2.5 (3 z

2 .0

(/3 03 0 1.5

IZ 0

1 .0

0 .5

0 .0

T i FLANK PALPATION FLANK PALPATION

+VCS

Fig. 6. The intensity of lordosis provoked by flank palpation alone and combined with vaginocervical stimulation (VCS) was determined in estrogen primed sham-operated (open bars), pudendal neurec- tomized (hatched bars) and pelvic+hypogastric neurectomized (cross-hatched bars) rats. * P < 0.05 vs. sham-operated group.

neurectomy group, 50_+ 6 vs. 57_+ 10; pre- vs. post- surgery values, respectively).

4. Discussion

During copulation, the female rat receives intense cutaneous and genital stimulation from the male [17]. The pattern of stimulation received by the female during copulation varies both quantitatively and quali- tatively among the diverse motor copulatory patterns, i.e. M, I or E [1,16]. Results in Experiment l suggest that M induce a significant analgesia in the female rat. The detailed analysis carried out by Moralf and Beyer [16] of the motor pattern and penile-vaginal interac- tions during M shows that the penis contacts the vagina only occasionally during this event. Therefore, the tac- tile stimulation on the perineum, abdomen and flanks of the female resulting from the male's pelvic thrusting and palpation may play a role in inhibiting nociceptive information. These somatic areas are innervated by the pudendal and several sensory nerves [17]. Another factor that could be involved in the analgesia observed during M is the propioceptive inflow resulting from the performance of lordosis. This could explain why non- receptive females, though receiving the same pattern of sensory stimulation from the mounting male as estrous Ss, failed to show analgesia. The fact that M-induced analgesia was no longer evident in Experiment 2, when shocks of higher intensity were used, suggests that this effect is weaker than the analgesia provoked by either I or E. This difference in analgesia is most likely medi- ated through the VS ocurring during the performance of I and E. Thus, during both events, intense and prolonged VS results from penile insertion. Alterna- tively, it is possible that given the duration of M, most shocks fell past this event. The fact that in Experiment 3, E was slightly more effective than I in inhibiting vocalization to STS may be due'to the fact that VS during E is much more prolonged than during I, and that it involves rhythmic stimulation (around 20 Hz) due to intravaginal pelvic thrusting. Moreover, the copulatory plug and seminal fluid at E could provide additional mechano-stimulation (including cervical) to enhance the intensity of CA,

The present findings, therefore, agree with previous reports where VCS with a glass rod induces analgesia in female rats [3,10,12]. This analgesia outlasts VCS since it persists for a prolonged period after cessation of the stimulus. In contrast to artificial vaginocervical analgesia, CA was short-lasting, abruptly declining upon cessation of the behavioral event. Thus, when shocks were applied 10-15 s after the performance of M, I or E, analgesia was no longer evident. The temporal char- acteristics of CA in the female suggest that it is medi- ated by spinal interneurons releasing inhibitory neuro-

P. G6mora et al. /Brain Research 656 (1994) 52-58 57

transmitters (e.g. GABA, glycine, norepinephrine or serotonin) rather than by neuromodulators, like opi- atergic peptides which exert more prolonged effects on the excitability of spino-thalamic neurons. The momen- tary analgesia associated with copulation may have the function of blocking the potentially noxious stimulation generated by vigorous male stimulation, which could otherwise interfere with the progression of copulation. On the other hand, artificial VCS, but not CA, besides activating the release of inhibitory neurotransmitters [2,15,18,19], also brings into play the release of neuro- modulators (e.g. enkephalins, noradrenaline) which in- hibit nociceptive information for a more prolonged time [9,23]. Therefore, the natural counterpart of artifi- cial vaginocervical analgesia may be that of parturition [7,20,25], in which an analgesic effect is biologically advantageous.

Previous studies from us and others have reported that CA also occurs in male rats [8,24]. However, in contrast to females, CA in males outlasts the perfor- mance of M, I and E and is cumulative, i.e. the intensity of analgesia increases across the copulatory series [8]. This difference in the temporality and inten- sity of CA between males and females suggests the operation of different neural mechanisms for triggering and maintaining CA in each sex. It is possible that this difference may not be strictly sexually dimorphic but, rather, behaviorally dimorphic. That is, CA in males may have particular characteristics because it ensues from the display of M, I and E rather than from the fact that it occurs in a male. Consequently, it is possi- ble that females that display M and the patterns of I or E (e.g. after treatment with testosterone in adulthood or as a consequence of neonatal androgenization) may express a 'male-type' analgesia (i.e. long-lasting and cumulative). Future studies should assess this possibil- ity.

Pelvic-hypogastric (but not pudendal) neurectomy significantly reduced the analgesic effect of I and prac- tically abolished the analgesia provoked by E. These data coincide with the report that hypogastric neurec- tomy partially blocked the analgesia observed during pregnancy [6], and support the idea that these two types of analgesias ensue from VCS. Aside from antag- onizing CA, pelvic-hypogastric neurectomy interfered with motor reflexes (i.e. immobilization, hind limb ex- tension, lordosis posture, and blockage of leg with- drawal after foot pinch) provoked by VCS, consistent with the findings of Cunningham et al. [4]. These data, combined with the fact that pelvic neurectomy reduces mating-induced prolactin release [22], antagonizes cop- ulation-induced ovulation [27], disrupts paced mating [5], and reduces vaginocervical analgesia (as measured by vocalization threshold and tail-flick latency [4]), suggest that motor, sensory, endocrine, and proceptive aspects of female copulation are modulated by afferent

signals arising in the pelvic region and travelling in the pelvic-hypogastric nerves.

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