Pain in animals is defined as “an aversive sensory experience caused by actual or potential injury that elicits progressive motor and vegetative reactions, results in learned avoidance behavior, and may modify species-specific behavior, including social behavior” [3]. Animals cannot verbally rate their pain intensity, quality, or location, nor can they communicate the impact of emotion on pain. Instead, researchers infer the presence of pain from abnormal behaviors that are (hopefully) unique to the experimentally induced nociceptive state. The difficulty in measuring an animal’s emotional or cognitive responses to pain suggests that we are largely using nociceptive models, rather than true pain models [4]. However, just because we can’t measure something doesn’t mean it isn’t there. Nevertheless, the word pain will be used throughout this chapter.

Pain can be typified as spontaneous or provoked, depending on whether or not it is elicited by exogenous stimulation. Many existing animal models of pain are limited in their duration; chronic, spontaneous pain–the most clinically relevant form–has proved particularly difficult to model in animals [5]. Pain conditions can also be visceral or somatic in nature. Visceral pain originates from the internal organs contained within the chest and abdomen, and it is characterized by increased autonomic reactivity, emotional salience, and diffuse pain that may be referred to other visceral or somatic tissue that shares common innervation at the level of the spinal cord [6]. Referred pain is perceived in areas distal from the site of injury that receives common spinal input as the region where pain originates [7, 8]. The majority of animal models of pain conditions associated with dyspareunia are visceral in nature, including uterine inflammation, vaginal and uterine distension, endometriosis, and abdominal pain (including cystitis and colitis).

In animal models, behavioral responses may reflect the location of the pain in the case of somatic tissue (e.g., withdrawal of a heated hind paw), whereas visceral pain may be manifested as referred somatic pain [7]. Patterns of pain behavior can increase in frequency or magnitude with higher levels of noxious stimulation. Abnormal behaviors that show temporal correspondence with tissue injury or inflammation are thought to reflect injury-specific pain, although the correlation may not be strong. For visceral pain in particular, the absence of behavior may be indicative of pain, as evidenced by reduced mobility or motivation to engage in normal activity [9]. In addition, estrous cyclicity may significantly impact some behaviors [10], but many indices of behavioral pain show equal variability when male versus female animals are used [11]. Empirical validation that a behavior is specific to pain is often achieved via the administration of known analgesics, such as nonsteroidal anti-inflammatory drugs, lidocaine, or morphine.

Ureteral Calculosis

Women with dysmenorrhea, or painful menstruation, often report dyspareunia and are more likely to experience urinary calculosis (kidney stones). Based on this comorbidity, animal models of ureteral calculosis (UC) may in-directly induce dyspareunia, although this link has never been formally tested.

The first detailed behavioral characterization of UC-induced visceral pain was conducted by Giamberardino’s laboratory [12]. Within a day of implantation of an artificial stone into the left ureter, rats displayed a variety of spontaneous pain behaviors including stretching, hunched back, abdominal/flank licking, flank muscle contractions accompanied by ipsilateral inward hindlimb motions, lower abdominal squashing (against the floor), and the adoption of a supine position with the left hindlimb retracted into the abdomen. These behaviors slowly decreased in frequency and duration over four days postimplantation. Rats with frequent visceral pain behaviors were more likely to vocalize to electrical stimulation of the ipsilateral oblique muscles, indicative of referred pain. These behaviors are similar to the protracted abdominal stretching observed in early visceral pain models [13, 14]. Pain behaviors were reduced with intraperitoneal 5 mg/kg/day morphine. Giamberardino’s model established a typology for abnormal pain behaviors associated with visceral pain that would be replicated or modified by the majority of subsequent abdominal visceral pain models.

Based on preliminary human evidence linking dysmenorrhea, endometriosis, and UC [15], Giamberardino and colleagues [16] developed a dual rat model of endometriosis with UC to investigate whether abdominal pain behaviors found in either condition are enhanced by the comorbidity. Animals with endometrial autografts plus stone implantations showed significantly longer bouts of pain behavior compared to stone implantation only or sham groups. Although all animals developed some referred hyperalgesia caused by the presence of a ureteral stone, the endometriosis + UC group displayed the greatest magnitude of referred pain as indicated by reduced vocalization threshold in response to electrical stimulation of the left oblique muscles.

Uterine Inflammation

Wesselmann and colleagues [17] characterized pain behavior associated with uterine inflammation in the rat. The pain behaviors they examined were based on the Giamberardino model of UC [12]. To induce inflammation, 10% mustard oil and a mineral oil vehicle were injected into the uterine lumen, and pain behaviors were videotaped for seven days postsurgery. Of animals receiving uterine inflammation, 79% displayed prolonged periods of spontaneous pain behavior, with behavior frequency peaking two days after surgery. Dramatic individual differences were found in the frequency and duration of pain behaviors, and animals with uterine inflammation showed reductions in overall mobility. Of animals displaying spontaneous pain behavior, 66% also showed referred muscle hypersensitivity in the lower back and flanks that actually outlasted the occurrence of spontaneous pain behaviors.