Endometriosis Endometriosis is a chronic infl ammatory and painful condition defi ned as th e presence of uterine glands and stroma outside the uterus. Th ere is no clear understandin g as to how endometrio- sis causes pain but proposed explanations include prostaglan- din p roduction, cytokine production, and adhesion formation. Endometriosis lesions can be found anywhere within the abdomi- nal and pelvic cavity. Most lesions are seen on the ovaries, pe lvic walls and cul-de-sac, but can also be found on bowel, bladder, ureters, liver, lung, a nd scar tissue. Th ere are no laboratory tests or imaging studies diagnostic for endometrio sis, and thus adolescent endometriosis is diagnosed by laparoscopic visualization. Dysmenorrhea is a cyclic pain, and recurrent nociceptive input from painful periods each mo nth can lead to neuronal alterations at the level of the spinal cord and brain that persist throughout the menstrual cycle (Vincent et al., 2011 ). Studies in adults with dysmenorrhe a have demonstrated central nervous system changes similar to those seen in other chronic p ain conditions. Such changes include altered central processing of noxious stimuli (Vincent et al., 2011 ), metabolic and morphological changes in the brain as seen on imaging studie s (Tu et al., 2009 , 2010 ), alterations in hypoth- alamic \200\223pituitary \200\223adreno cortical axis function, and reduced qual- ity of life (Vincent et al., 2011 ). Dysmenorrhea is therefore a cyclic pain that appears to develop features of a chronic neuropathic pain condition over time. In adult women, the most common cause of chronic pelvic pain is endometriosis (Fauconnier a nd Chapron, 2005 ), estimated to aff ect 4% to 17% of post-menarchal females (Ranney, 1980 ). Population studies of endometriosis in adolescents are likely to underestimate its preva lence due to underreporting of symptoms and failure to diagnose. In adolescents who seek tr eatment for unexplained SECTION 4 pain in specific populations and diseases 300 chronic pelvic pain, there is a 47% prevalence rate of endometriosis found at time of lapar oscopy (Goldstein et al., 1979 ). Other studies have shown that 25% to 38% of adolescents w ith chronic pelvic pain who seek medical care and undergo laparoscopy have endometrio- sis (Kontoravdis et al., 1999 ; Vercellini et al., 1989 ). Empiric treat- ment with NSAIDs and oral contraceptives (for the treatment of dysmenorrhea as described earlier) can improve sy mptoms for many adolescents with chronic pelvic pain, but in cases where pain persists, gre ater than 70% of adolescents with chronic pelvic pain will be diagnosed with endometriosis (Laufer et al., 2003 ). In a more recent study, 97% of adolescents with persistence of pain on NSAIDs and combination hormonal therapy were found to have endometriosis on laparoscopi c evaluation (Opoku-Anane and Laufer, 2012 ). Th e increase in prevalence from 70% to 97% m ay be due to the improvement of optics of laparoscopes with digital imaging. ovarian cysts more frequently than controls without endometriosis (Ballard et al., 2008 ). Women experiencing these symptoms have a high risk of having endometriosis, especially if t hey experience more than one of these symptoms (Ballard et al., 2008 ). While ado- lescents may report similar symptoms as adults, 60% of adolescents with endometriosis report either abdominal or pelvic pain, and 90% report pain that occurs during menses (cyclic) as well a s pain that is continuous throughout the menstrual cycle (acyclic) (Laufer et al., 1997 ). Questioning adolescents about their menstrual history can iden- tify markers associated wit h endometriosis (Chapron et al., 2011 ). A positive family history of endometriosis in a fi rst-degree rela- tive (odds ratio (OR) = 3.2; 95% confi dence interval (CI): 1.2 \200\2238 .8) school absenteeism during menstruation (OR = 1.7; 95% CI: 1 \200\2233), and use of oral contraceptive pills for treating severe primary dys- menorrhea in girls under18 years (OR = 4.2; 95% CI: 1.8 \200\22310.0) are predictive for endometriosis (Chapron et al., 2011 ). Although commonly understood to be a disease of adult women, endometriosis can occur in ado lescents and in pre-menarchal girls as early as 8 years of age (Marsh and Laufer, 2005 ). A s endome- triosis is an estrogen-dependent disease, endometriosis should be considered in t he diff erential diagnosis of all females with abdomi- nal or pelvic pain once the benchmar k of thelarche has been met (Economy and Laufer, 1999 ; Lubianca et al., 1998 ). More typic ally, women are diagnosed during their childbearing years when they seek medical treatment for infertility. However, data from the Endometriosis Association indicate that two-thirds of adult women with endometriosis reported onset of pelvic symptoms during ado- lescence, w ith 38% reporting symptom onset before age 15 years (Ballweg, 2004 ). On average there is a delay of 9 years from onset of symptoms to diagnosis of endometriosis, with longer delays (8 \200\22310 years) diagnosing adolescents compared to women in their 30s (<2 years; Ballw eg, 2004 , Hadfi eld et al., 1996 ). Adolescents under age 15 years with chronic pelvic pai n saw an average of 4.2 doctors compared with women in their early 30s who saw an aver- age of 2.6 doctors before diagnosis or referral (Ballweg, 2004 ). Many women with endometriosis report a preponderance of gas- trointestinal symptoms and hav e received a previous diagnosis of IBS or pelvic infl ammatory disease (PID) which contribu tes to the delay in diagnosis of endometriosis in both adults and adolescents. In a consecu tive series of 355 women undergoing laparoscopy for suspected endometriosis, 90% of the wom en with histologically confi rmed endometriosis had gastrointestinal symptoms (bloat- ing c onstipation, diarrhea, nausea, vomiting). While bloating was the most frequent gastrointest inal symptom, reported by 83% of women, 71% also had other gastrointestinal symptoms (Marou n et al., 2009 ). Gastrointestinal symptoms are reported nearly as fre- quently as gynecolo gical symptoms in women with endometrio- sis (Maroun et al., 2009 ). Similarly, a national case \200\223control survey from the UK concluded that 45% of women with endometriosis had a record of abdominal pain and only 15% had a record of pelvic pain (Ballard et al., 2008 ) . Results from the same study also showed that women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS and six times more likely to receive a diagnosi s of PID than women without endometriosis (Seaman et al., 2008 ). Th ere is no data specifi c for adolescents. Th e associa- tion between endometriosis and PID or IBS was less strong aft er the diagnosis of endometriosis was made, and these authors suggest some misdiagnosi s among women with endometriosis, while pos- ing the possibility of comorbidity between end ometriosis and PID or IBS. Whether IBS coexists with endometriosis or is secondary to devel opment of visceral hyperalgesia due to this chronic infl amma- tory disease is not known. A ccordingly, endometriosis should be considered in the diff erential diagnosis of all female s with abdomi- nal or pelvic pain when a functional gastrointestinal disorder such as IBS i s considered once the benchmark of thelarche has been met (Economy and Laufer, 1999 ). Adolescent endometriosis can be a challenging diagnosis as signs and symptoms are oft en no n-specifi c for gynecological pathology and can diff er from those reported by adults ( Tab le 30.1 ). Adult women with endometriosis report gynecological symptoms of abdominopelvic p ain, severe dysmenorrhea, menorrhagia, irregu- lar menses, subfertility or infertility, and acute adnexal pain due to Table 30.1 Symptoms of adolescents with endometriosis Presenting symptoms Per cent Acyclic and cyclic pain 62.5 Acyclic pain 28.1 Laparoscopic fi ndings in adolescents also diff er from adults, and a prior \200\230negati ve \200\231 laparoscopy should not rule out the possibility of endometriosis if a surgeon o r gynecologist unfamiliar with the appearance of adolescent endometriosis lesions performed the pro- cedure. Under direct vision, endometriosis lesions in adolescents typically appea r as red and clear lesions and the more classic black or brown lesions are more commonly se en in adult women (Laufer et al., 2003 ). Th e clear lesions can be diffi cult to visualize without the use of specialized surgical techniques. Endometriomas, a col- lection of endom etriosis in the ovary, also commonly referred to as a \200\230chocolate cyst \200\231 are rarely seen in adolescents but have been Cyclic pain 9.4 Gastrointestinal pain 34.3 Urinary symptoms 12.5 Irregular menses 9.4 Vaginal discharge 6.3 Source: data from Laufer, M. et al., Prevalence of endometriosis in adolescent girls with c hronic pelvic pain not responding to conventional therapy, Journal of Pediatric and Adolesc ent Gynecology , Volume 10, Issue 4, pp. 199 \200\223202, Copyright 1997 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights rese rved. CHAPTER 30 chronic pelvic pain in children and adolescents 301 reported (Wright and Laufer, 2010 ). A high index of suspicion and knowledge of the diff er ences in presentation between adult women and adolescents is key to identifying and treatin g endometriosis. Th ere is lack of long-term data on follow-up of endometriosis treat- ment . One long-term follow-up study shows that with early diag- nosis and treatment, disease pr ogression may be retarded (Doyle et al., 2009 ) Acute exacerbations in endometriosis pain may be surgical or non-surgical and an eff ort sh ould be made to identify the cause of an acute increase in pain. Non-surgical causes of acu te pain fl ares include a missed or delayed oral contraceptive pill, change in absorption o f oral contraceptives due to medications, or change- over in hormonal therapy. Suspected ov arian torsion, tubal, or ovarian cysts, and adhesions require surgical evaluation. Close co mmunication with the patient \200\231s gynecologist is important to understanding the etiol ogy of episodic pain fl ares, and informs pain management. Th e pathogenesis of endometriosis remains unclear. Several theories have attempted to expl ain possible aetiologies, includ- ing developmental anomalies, retrograde menstruation, fai lure of endometrial cell apoptosis, immune and infl ammatory disease, and genetics (Bulun, 2009 ). Th ere is a 6.9% increased risk of endome- triosis of fi rst-degree relatives with endometriosis (Simpson et al., 1980 ). Other research suggests endometriosis, like migraine head- ache, is a neurovascular disease (Zhang et al., 2008 ), and indeed, compared to wome n without endometriosis, women with endome- triosis have an increased density of sensory ne rve fi bres in the peri- toneum and eutopic endometrium (Berkley et al., 2005 ; Tokushige e t al., 2006 ). Pelvic \202 oor dysfunction Pelvic fl oor dysfunction is being recognized more frequently as a cause of chronic pelvic pain in children and adolescents. In adults, pelvic fl oor dy sfunction is associated increasing age and parity, and structural or mechanical changes in the pelvis (Baessler et al., 2004 ; Kepenekci et al., 2011 ; MacLellan et al., 2000 ). Inju ry to the sac- rum, coccyx, pubis, and hip joints can be a cause of misalignment, tension, and infl ammation of the attached ligaments, muscles, and nerves in the pelvis. Pain syndro mes associated with pelvic fl oor dysfunction include interstitial cystitis/painful bladder syndrome (IC/PBS), chronic prostatitis/painful prostate syndrome (CP/PPS), vulvodynia, pro ctalgia fugax, coccyxdynia, piriformis syndrome, pudendal nerve entrapment, and others. Visceral hyperalgesia is a common fi nding in patients with endometriosis (Issa et al., 201 2 ). Th e role of chronic infl ammation in the development of visceral hyperalgesia and neu ropathic pain was the subject of a recent review of endometriosis pain mecha- nisms (Evans et al., 2007 ). Th e authors identifi ed research show- ing invasion of nociceptors into pe ritoneal endometriosis lesions and increased number of nerve terminals in endometriotic tis sue, as well as activation of nociceptors by infl ammatory mediators, sprouting of new noci ceptors, and activation of silent nociceptors present in normal endometrium and peritoneum (Anaf et al., 2006 ; Berkley et al., 2005 ; Tokushige et al., 2006 ). Th e authors speculat e that such nerve sprouting might be caused by increased levels of nerve growth factor (NGF ), since expression of NGF in endome- triotic tissue is reported to be higher than in eutop ic endometrium (Anaf et al., 2006 ; Tokushige et al., 2006 ). In children, pelvic fl oor tension myalgia is associated with void- ing or elimination dysf unction, and spasm of the pelvic fl oor mus- cles. Th e typical presentation in children is night time awakening with severe lower abdominal or perineal pain. Urodynamic studies oft en identify high urethral pressures without structural obstruc- tion of the outfl ow tract (Hoebeke et al., 2004 ). Conditions associ- ated with pelvic fl oor dysfunction have been s hown to respond well to biofeedback-assisted pelvic fl oor relaxation therapy (Li et al., 2 006 ). Increased signaling from visceral nociceptors to the spinal cord leads to sensitization of dorsal horn cells, convergence of visceral and somatic aff erent pathways, and alterations in neural modulation of inhibitory and excitatory pain pathways throughout the central nerv ous system due to neuroplasticity (Bajaj et al., 2003 ; Berkley, 2005 ). Over time, pain sp reads to other viscera (viscero-visceral hyperalgesia) and to the abdominal wall and back ( viscera-somatic hyperalgesia) with somatic symptoms of cutaneous hypersensitiv- ity to touc h, i.e. allodynia (Giamberardino et al., 2010 ). Chronic prostatitis/prostatic pain syndrome In adolescent males, CP/PPS is defi ned by symp toms of voiding dysfunction (frequency, urgency, split stream and sense of resid- ual urine ) and pain (testicular, penile, scrotal, pelvic or rectal) as well as ejaculatory pain or d iscomfort. Males rarely exhibit these symptoms before puberty (Hoebeke et al., 2004 ; Tripp et al., 2009 ). However, in a study of North American adolescent males aged 16 to 19 years , the prevalence of CP was found to be 8.3%, comparable to adults (Tripp et al., 2009 ). Un like adult CP, adolescents reported a preponderance of voiding symptoms, which led authors to con- clude that CP in adolescents is most likely due to pelvic fl oor dys- function (Li et al., 2006 ). Currently there is no cure for endometriosis and treatment is aimed at controlling progress ion of disease and pain relief. Guidelines from the American College of Obstetricians and G ynecologists (ACOG) for management of adolescent endometriosis pain are extrapolated from t he adult experience with endometriosis pain. Recommendations include surgical destruction a nd/or removal of visible lesions, hormonal suppression of ovulation and menstrua- tion, and anti-infl ammatory analgesics (ACOG, 2005 ). Surgical destruction of endometriosis and men strual suppressive therapy can retard disease progression (Doyle et al., 2009 ). Yet, these inter- ventions are variably eff ective and many adolescents continue to report pain despi te anti-endometriosis therapy. Managing chronic pelvic pain due to endometriosis is a multi disciplinary endeavor and communication among clinicians across disciplines, including pain medicine, gynecology, and psychology, is essential for good pain treatment outcomes. Interstitial cystitis/bladder pain syndrome IC/BPS is a condition frequently occurring with endometriosis and IBS, and can be a related cause of chronic pelvic pain. Characteristic s ymptoms of IC include urinary frequency and urgency, usually with pelvic pain and nocturia, in the absence of bacterial infection or any other identifi able pathology. In adults, it is estimated that 85% of patients with chronic pelvic pain may have symptoms of IC (Parsons and Albo, 2002 ). Th e incidence of IC in children and adolescents is not known. In adults , IC is being identifi ed more fre- quently with the use of the Interstitial Cystitis Sympt om Index, a symptoms questionnaire (Clemons et al., 2002 ), and an intravesical SECTION 4 pain in specific populations and diseases 302 potassium sensitivity test (PST; Chung et al., 2010 ). Th e PST is an offi ce-based test us eful for isolating the bladder as the source of pain and urgency symptoms. Potassium instil led into the bladder is a neuroirritant and causes an increase in pain symptoms. A posi- ti ve PST suggests increased permeability of the bladder urothelium and lends support to the d iagnosis of IC. Alternatively, instilling anesthetic solution may also aid in the diagnosis of IC. Th e diag- nosis is confi rmed by cystoscopy. If IC is detected, then the patient c an be treated for chronic pelvic pain of bladder origin. Urological therapy for IC has a hi gh rate of success and oft en is best treated in a multidisciplinary setting. On physical exam, evaluation of the spine and pelvis looking for posture, gait, symmetry, r ange of motion, and tenderness to pal- pation may reveal biomechanical alterations. Leg-len gth discrep- ancy and pathology of the spine or hip can be referred to the groin and pelvis . A sensory exam of the back and abdomen to determine the presence of allodynia or hyperalg esia can provide evidence of central sensitization and neuropathic pain. Pain of visceral o rigin and associated viscero-somatic convergence may present as a non- dermatomal area of h yperalgesia or allodynia over the abdomen or back. A dermatomal distribution of pain over the abdomen is suggestive of an intercostal or subco stal neuralgia, and may indicate pathology at any point along the nerve as it exits the spi nal canal. Palpation of the area may reveal proximal and distal radiation along the course of the nerve, known as Valleix phenomenon. Neuroimaging of the spine is indicated if more p roximal nerve involvement is suspected. Less commonly, tumor or herpes zoster is the cause. Assessment A careful history can help direct the workup and evaluation of patients with chr onic pelvic pain. Quality and location of pain can help determine whether pain symptoms ori ginate from viscera, are musculoskeletal, or from an entrapped nerve. Pain descriptors such as burning, aching, stabbing, spreading, or throbbing are common in patients with visceral hyperalgesia or neuralgia; inability to toler- ate any tight fi tting clothing and hyperse nsitivity of the abdominal wall or back to light touch or gentle pressure can indicate visc ero- somatic convergence with referred pain to the abdomen or back. In addition to asking a bout location, onset, and frequency of pain symptoms, questioning for temporal association with injury or trauma such as an occult pelvic fracture, or suspected slipped capital femor al epiphysis, hip, or back injury can identify treatable orthopedic conditions. Gastrointes tinal and urinary symptoms oft en coexist with other pelvic pathology. Abdominal cutaneous nerve entrapment syndrome (ACNES) or an intercostal neuralgia can be ov erlooked causes of chronic abdom- inopelvic pain. Th e abdominal wall is innervated by the anterior rami of the lower six thoracic nerves (T7 \200\223T12) and the fi rst lumbar nerve (L1 \200\223L2). Th oraco-abdominal nerves exit the spinal canal and terminate in posterio r, lateral and anterior branches, providing sen- sory innervation to the abdominal wall and overlying skin. Similarly, L1 to L2 subcostal nerve involvement (ilioinguinal/iliohypogast ric nerves) may present as vulvar or groin pain in girls or scrotal pain in boys. Terminal branches of these somatic nerves course through the lateral abdominal wall within a plane b etween the internal oblique and transversus abdominis muscles. Th e thoracic branches are a nchored at various points through fi brous attachments within the wall which can tether or trap the nerve along its course as it passes to the superfi cial layers. Th e anterior cuta neous branch of an intercostal nerve is most vulnerable to entrapment because it makes a ne arly 90-degree turn to enter a fi brous tunnel as it passes to the superfi cial tissues at the lateral border of the rectus abdominis mus- cle. A history of straining, coughing, or v omiting may be elicited as increased intra-abdominal pressure, intense muscle contraction, or blunt trauma to the abdominal wall can lead to nerve entrapment. Postoperatively, tracti on can be placed on the nerve by a scar. Obtaining a menstrual history and understanding norms for menstrual frequency, amount of bl eeding, and severity of pain is important in order to determine whether further gynecologic al investigation is needed when evaluating a patient referred for chronic abdominopelvic pa in. For example, irregular periods are considered the norm for young teens because of anovu lation; however, it is not well appreciated that during the early years aft er menarche, 90 % of cycles will be within the range of 20 to 45 days even during the fi rst gynecological year (Popat et al., 2008 ). Cycles outside of the range of 20 to 45 days are statistically uncommon, even in young girls, and deserve evaluation for potential treatable causes. On exam, one can look for a positive Carnett \200\231s sign. With the patient in the supine position, the examiner palpates along the lat- eral border of the rectus sheath and asks t he patient to attempt a sit up. As the patient tenses the abdominal wall muscles, if entrap ped, the anterior branch of the intercostal nerve becomes compressed between the examiner \200\231s fi nger and the taught abdominal muscles, resulting in worsening pain. If pain is from the viscera, tensing the muscles guards against more painful deeper palpation. Abdomi nal wall pain can be distinguished from visceral pain with a transversus abdominis plane (T AP) block, which numbs the abdominal wall. A rectus sheath block may relieve an abdominal c utaneous nerve entrapment; abdominal wall trigger points may have a similar pres- entation and can be identifi ed with careful palpation. A medication history may reveal that the patient is on an oral contraceptive pill. It is im portant to determine whether the pill was started for menstrual irregularities or pain, and note whether symptoms have improved since starting hormonal therapy. A family history of g ynecological disorders such as endometriosis, severe dysmenorrhea, or infertility can guide referral to an ado- lescent gynecologist. A patient with a positive family history of endo metriosis in a fi rst-degree relative has a 6.9% increased risk of endometriosis in compari son with a 1% risk in controls (Simpson et al., 1980 ). During the interview or exam, time should be set aside to speak confi dentially with the pa tient about sexual activity, history of phys- ical or sexual assault, and sexually transmit ted infections as infor- mation on these sensitive subjects may be withheld in the presence of parents or guardians. In a systematic review of risk factors in women with and without chronic pelvic pain, Lathe et al identifi ed a strong association between all types of chro nic pelvic pain and pelvic pathology, history of childhood abuse, and psychological morbidi ty in adults (Latthe et al., 2006 ). General approach to treatment ( Table 30.2 ) When acute infl ammatory pain is suspected, NS AIDs and opioid analgesics can provide good pain relief. It is known that non-ster- oidal a nti-infl ammatory analgesics are not as eff ective for treating neuropathic pain and viscer al hyperalgesia (Cruccu et al., 2007 ; CHAPTER 30 chronic pelvic pain in children and adolescents 303 Table 30.2 Approach to multidisciplinary treatment of pelvic pain in adolescents Patients benefi t from physical therapy as part of a multidiscipli- nary approach to treatm ent of chronic pelvic pain. Prolonged peri- ods of bed rest and compensatory postures can l ead to myofascial pain and deconditioning, adding to the overall level of pain-related disa bility. When the patient has become homebound and no longer participates in athletic or aft er school activities the rationale for functional restoration is evident. Aquatherapy, gen tle stretching, core and pelvic fl oor strengthening, and building endurance in a therapeut ic setting can be the fi rst steps toward re-engaging the patient in everyday activities. Medications NSAIDS Anticonvulsant Tricyclic antidepressants Tramadol/oxycodone Lidoderm patch Nerve blocks Trigger point injections Referred pain from the viscera, and viscero-somatic convergence of neural sensory pathways at the level of the spinal cord can result in allodynia and hyperalgesia of the abdominal w all. Transcutaneous electrical nerve stimulation (TENS) or topical application of a 5% lido caine patch (Lidoderm ) can provide additional pain relief when the abdominal wall or ba ck are tender. TENS involves stimulation of the skin using electrical currents at various p ulse rates (frequen- cies) and intensities in order to provide pain relief. A conventional TENS emits pulses between 50 and 120 Hz at a low intensity produc- ing a tapping or gentle buzzing sensation. It is speculated that TENS relieves pain by stimulating myelinated aff e rents, which in turn acti- vate segmental inhibitory pathways, thereby altering the body \200\231s abil- ity to receive or perceive pain signals. TENS units are the size of a small pager with attached electrodes that adhere to the skin at the site of pain. Th e units can be worn throughout the day, with the patient controlling the level of current for maximal comfort. Typically, physi- cal therapists will trial a TENS unit over the abdomen and make rec- ommendations for obtaining a unit for home use. Th e available data on high-frequency TENS suggest it is eff ective for the treatment of dysmenorrhea (Proctor et al., 2002 ; Wal sh et al., 2009 ). Transversus abdominis plane (TAP) Pudendal nerve Ganglion impar Physical therapy Aquatherapy Pelvic \202 oor retraining Core strengthening Endurance Flexibility TENS unit Biobehavioural therapies Cognitive behavioral therapy Biofeedback Guided imagery Treatment of depression and anxiety Assistance with school reentry Complementary and alternative therapies Acupuncture Th e use of acupuncture in managing painful periods is promising though data is limited. Fi ndings should be interpreted with caution due to the small number of studies and study part icipants. No signifi - cant adverse eff ects were identifi ed in this review (Smith et al., 2011 ). When indicated, abdominal wall trigger point injections and TAP blocks can provide temporary pain relief, and help establish a diagno- sis of abdominal wall neuralgia, a con sideration when treating patients with abdominal incisions/scars, abdominal wall adhesions, or when nerve entrapment is suspected. Pain that is localized to the perineum may respond to a pudendal nerve or ganglion impar block. Acupressure Th erapeutic massage Dworkin et al., 2007 ). Development of central sensitization and chronic neuropathic pain m ay explain why pain continues despite treatment with standard anti-endometriosis therapies. Neuropathic pain analgesics include tricyclic antidepressants and anticonvulsants. First-li ne agents most commonly used for treatment of neuropathic pain conditions include amitripty line and gabapentin, typically chosen based on side eff ect profi le as there is yet no dat a to support one class of drug over the other as far as pain relief effi cacy. Th ere is no data on the use of these drugs in patients with endometriosis. Conclusions Chronic pelvic pain is oft en described as abdominal pain in younger patients. Dysmenorrhea is more common in adolescents than adults and can be associated with changes i n the central nervous system and other chronic pain conditions due to neuroplasticity. Cent ral sensitization of visceral pain pathways can aff ect bowel and bladder function, and be associated with pelvic fl oor pain and dys- function, which may be improved with physical t herapy. In female adolescents with chronic abdominopelvic pain of undetermined etiology, it is important to have a high index of suspicion for endometriosis, especially when a prior diagnosis of IBS is present. Th e diagnosis of endometriosis is commonly delayed until adul t- hood though symptoms start during adolescence. Adolescents with endometriosis can report either cyclic or acyclic pain and present with a preponderance of gastrointestinal symptom s. Obtaining a full menstrual history is an important aspect of the evaluation of female ad olescents with chronic abdominopelvic pain. Complicating the treatment of chronic pelvic pain is the obser- vation that many adolescent s with endometriosis and persistent pain have symptoms of anxiety and/or depression. Psycho logical support to develop pain coping strategies and to treat associated symptoms of depre ssion or anxiety is part of a multidisciplinary approach to pain management. When medicatio n is initiated, the selective serotonin re-uptake inhibitor class of antidepressants is fre quently prescribed for depression and/or anxiety. When medi- cation for anxiety or depressi on is a consideration, therapeutic dos- ing of amitriptyline as a neuropathic analgesic in the treatment of endometriosis pain can be limited due to concern for increased risk of ser otonin syndrome. Additionally, many adolescents are con- cerned about weight gain, and have a history of IBS with constipa- tion, both of which can be exacerbated by a tricyclic anti depressant and ultimately lead to medication non-compliance. SECTION 4 pain in specific populations and diseases 304 Case example General physical and brief neurological examination revealed no abnormalities except for he r abdominal examination: her abdo- men was soft , non-distended, with decreased bowel sound s. Laparoscopic port sites located in the umbilicus, midline below the umbilicus, and left lower quadrant were well healed. Th e abdominal tenderness was diff use, but greatest over the left lower quadrant and periumbilical area. Light touch or superfi cial palpation cause d pain and she was unable to tolerate deep palpation. Carnett \200\231s test was negative. Abdominal examination otherwise was unremarkable. A 14-year-old-female who has been to the emergency department (ED) many times over the past year for recurrent fl are-ups of abdom- inal pain has received intravenous analgesia with ketorolac and morphine with transient relief. She has been thoroughly investigated for abdo minal pain by multiple specialists from gastroenterology and general surgery over the prece ding year. Th ese investigations included computed tomography scans, abdominal and pelvic u ltra- sounds, HIDA (hepatobiliary iminodiacetic acid) scan and gall bladder emptying studie s, and blood tests to rule out coeliac disease, infectious, and IBDs. Last year she underwe nt laparoscopic chole- cystectomy for presumed gallbladder dysfunction, and at the same tim e had her appendix removed pre-emptively. Th e procedure was uneventful but she continued t o report severe pain postoperatively. Repeated upper and lower endoscopies did not reveal a bnormali- ties. She is being treated for IBS and gastro-oesophageal refl ux dis- order. At the time of her most recent ED visit, she presented with periumbilical and left lower quadr ant pain which did not respond to repeated doses of intravenous morphine. Th e decision was made to admit the patient to the hospital for further evaluation of chronic abdominal pain and pain management. Diff erential diagnosis: \231 Visceral hyperalgesia due to central sensitization. \231 Viscero-somatic convergence and referred pain from viscera. \231 Abdominal cutaneous nerve entrapment (ACNE). \231 Intercostal (T7 \200\223T12) or subcostal (L1) neuralgia. Further history revealed that the patient had started taking oral contraceptives for irregu lar menses at the age of 13 years. She slept over a friend \200\231s house and forgot to ta ke her pill the day before her pain developed. Her mother had a history of heavy and painfu l periods and both of her maternal aunts were diagnosed with endometriosis when they underw ent laparoscopy as part of an infertility workup. Additional history revealed that her pediatrician has suggested she meet with a psychologis t because of depressed mood and school avoidance. Th e patient started high school this yea r and has missed many days of school due to pain. She has stopped play- ing soccer and chee rleading due to pain, activities she previously enjoyed. She has withdrawn from peers and s ocial activities. Th e patient spends most her time at home resting on the couch and worryi ng about undiagnosed serious illness. She feels that some healthcare providers no longer be lieve she has pain and view her as \200\230faking. \200\231 Sleep is diffi cult to initiat e and non-restorative. She will probably have to repeat ninth grade due to absences. Th is patient was referred to an adolescent gynecologist for evaluation. With her history o f persistent abdominopelvic pain while on an oral contraceptive and positive family history of endometriosis, this patient has a high chance of being diagnosed with endometriosis. At the time of laparoscopy she was found to have stage I endometriosis. Th e surgeon procee ded to cauterize visible lesions in the abdomen and pelvis. She was treated with a continuo us oral contraceptive (without breaks or placebos for suppression of menses), and was start ed on gabapentin for treatment of the neuropathic component of her pain symptoms. Over the next 2 to 3 months, she had several episodes of painful spotting. Her pain symptoms fl ared and did not respond to NSAIDs. Her gynaecolo- gist made some changes to her hormonal thera py to improve sup- pression of ovulation. She received a prescription for tramadol 25 to 50 mg every 8 h, with instructions to take no more than 3 to 5 days during the month. Th e patient describes periumbilical and left lower quadrant pain that is present all the t ime to a variable degree. Th e pain symptoms developed gradually over the past 18 months. S he cannot recall an inciting event or illness. Th e pain is described as a sharp, stab- bin g, and sometimes throbbing sensation that comes on randomly without obvious triggers. Any t ight-fi tting clothing over her abdo- men worsens the pain. Th e pain is always present, bu t can range in intensity from 5 to 10/10 on a numerical rating scale. Th e pain is not rela ted to food intake, bowel movements, or voiding, though sometimes these activities cause pa in to increase. Pain is some- times worse with menses but can occur any time of the month. She has occasional nausea but has not vomited. Bowel and bladder patterns have not changed. She has a history of constipation and is treated with Miralax . She has an upcoming app ointment with the Pain Treatment Clinic for evaluation of new low back pain. Subsequently, with the combination of hormonal suppression, NSAIDs, gabapentin, and occasio nal tramadol, her pain symptoms subsided. She was able to return to school and began to wor k with a psychologist, and started taking an antidepressant for her mood symptoms. One mont h aft er her surgery, the patient was able to return to school for two classes a day, and w ithin 2 weeks she was attending school full time, participating in gym class, and playing s oft ball with her freshman team. She still has occasional severe cramping, but her pain is manageable on her current regimen and does not interfere with her desired activities. Past medical history is signifi cant for menarche at age 11 years. Menses are irregular and she takes an oral contraceptive pill. She is followed by GI for IBS, diagnosed at age 12 y ears with asso- ciated GERD which is treated with Prevacid and constipation, treated wit h Miralax . Previous surgeries include laparoscopic cholecystectomy and appendectomy. Fa mily history reveals that her mother and aunts had diffi culty conceiving. References Alagiri , M. , Chottiner , S. , Ratner , V. , Slade , D. , and Hanno , P. M. ( 1 997 ). Interstitial cystitis: unexplained associations with other chronic disease and pain syndromes . Urology , 49 , 52 \200\22357. On physical exam she is very anxious, lying on her right side, and crying. Vital signs: hea rt rate 93/min, regular; respiratory rate 15/min, crying; blood pressure 115/65; room air S pO 2 = 100%. American College of Obstetricians and Gynecologists. ( 2005 ). ACOG Committee Opinion. Numb er 310, April 2005. Endometriosis in adolescents . Obstet Gynecol , 105 , 921 \200\223927. CHAPTER 30 chronic pelvic pain in children and adolescents 305 Kepenekci , I. , Keskinkilic , B. , Akinsu , F. , Cakir , P. , Elhan , A. H. , Erkek , A. B . , et al . ( 2011 ). Prevalence of pelvic fl oor disorders in the female population and th e impact of age, mode of delivery, and parity . Dis Colon Rectum , 54 , 85 \200\22394. Anaf , V. , Chapron , C. , El Nakadi , I. , De Moor , V. , Simonart , T. , and No l , J. ( 2006 ). Pain, mast cells, and nerves in peritoneal, ovarian, and deep infi ltrating endo metriosis . Fertil Steril , 86 , 1336 \200\2231343. Baessler , K. , Bircher , M. D. , and Stanton , S. L. ( 2004 ). Pelvic fl oor dysfunction Klein , J. R. , and Litt , I. F. ( 1981 ). Epidemiology of adolescent dysmenorrhea . in women aft er pelvic trauma . BJOG , 111 , 499 \200\223502. Pediatrics , 68 , 661 \200\223664. Bajaj , P. , Madsen , H. , and Arendt-Nielsen , L. ( 2003 ). Endometriosis is associated wi th central sensitization: a psychophysical controlled study . J Pain , 4 , 372 \200\223380 . Kontoravdis , A. , Hassan , E. , Hassiakos , D. , Botsis , D. , Kontoravdis , N. , and Crea tsas , G. ( 1999 ). Laparoscopic evaluation and management of chronic pelvic pain during ad olescence . Clin Exp Obstet Gynecol , 26 , 76 \200\22377. Latthe , P. , Mignini , L. , Gra y , R. , Hills , R. , and Khan , K. ( 2006 ). Factors predisposing women to chronic pelvic pain: systematic review . Br Med J , 332 , 749 \200\223755. Ballard , K. D. , Seaman , H. E. , De Vries , C. S. , and Wright , J. T. ( 2008 ). Can symp tomatology help in the diagnosis of endometriosis? Findings from a national case-control st udy \200\224Part 1 . BJOG , 115 , 1382 \200\2231391. Ballweg , M. L. ( 2004 ). Impact of endometriosis on women \200\231s health: comparative hi storical data show that the earlier the onset, the more severe the disease . Best Pract Res Clin Obstet Gynaecol , 18 , 201 \200\223218. Laufer , M. , Goitein , L. , Bush , M. , Cramer , D. , and Emans , S. ( 1997 ). Prevalence of endometriosis in adolescent girls with chronic pelvic pain not responding to conventiona l therapy . J Pediatr Adolesc Gynecol , 10 , 199 \200\223202. Berkley , K. J. ( 2005 ). A life of pelvic pain . Physiol Behav , 86 , 272 \200\223280. Be rkley , K. J. , Rapkin , A. J. , and Papka , R. E. ( 2005 ). Th e pains of endometriosis . Laufer , M. , Sanfi lippo , J. , and Rose , G. ( 2003 ). Adolescent endometriosis: diagnosi s and treatment approaches . J Pediatr Adolesc Gynecol , 16 , S3 \200\22311. Science , 308 , 1587 \200\2231589. Bulun , S. E. ( 2009 ). Endometriosis . N Engl J Med , 360 , 268 \200\223279. Campo , J. V . , Di Lorenzo , C. , Chiappetta , L. , Bridge , J. , Colborn , D. K. , Gartner , J. C. , e t al . ( 2001 ). Adult outcomes of pediatric recurrent abdominal pain: do they just grow ou t of it? Pediatrics , 108 , E1 .