The Future of Abdominal and Pelvic Pain Management

• Treat

(1) specific pain conditions/diseases

(2) disease interactions

(3) pain per se

Specialist treatment of each identified condition comprises multiple approaches, e.g., pharmacological, surgical, behavioral, physical therapy, and interventional pain management measures. It is not the aim of this paper to describe a protocol for each condition, which is referred to in specific chapters of this book. However, it must be underlined that in each specialty field a multimodal management regimen has been shown to provide better results than a single modality intervention and should always be preferred [30,33].

In the case of multiple identified diseases as the basis of abdominal and pelvic pain, an important element in the therapeutic approach to the patient is to try to identify common treatments, i.e., useful for more than one condition, as happens when targeting common pathophysiological mechanisms. One example is provided by the overactivity of mast cells that is an established concept in pain of neuropathic origin [14,31] but has also been documented in several visceral diseases manifesting with pain at abdominal and pelvic level. In patients with IBS, for instance, rectal hypersensitivity is associated with the presence and activation of mast cells in the mucosa [52]. In BPS/IC a high number of intravesical mast cells has been found [35], while the presence of increased activated and degranulating mast cells has also been shown in deep infiltrating endometriosis [3,49]. These observations provide the rationale for the use of compounds that down-regulate mast cell activity, such as the endogenous cannabimimetic and anandamide analogue N-palmitoyl-ethanolamine (PEA), in various abdominal and pelvic pain conditions. PEA has indeed been shown to significantly attenuate the effects of experimentally induced visceral hyperalgesia in rats, i.e., NGF/turpentine-induced bladder hyperalgesia: bladder hyper-reflexia, referred thermal somatic hyperalgesia and c-fos expression in the spinal cord [15,16]. In recent preliminary research studies in an animal model of viscero-visceral hyperalgesia from experimental endometriosis plus ureteral calculosis in female rats, prolonged administration of PEA has also proven to reduce mast cells overexpression at the level of the endometrial lesions, in parallel with a reduction of the behavioral indices of abdominal and pelvic pain and referred hyperalgesia [22, Giamberardino et al, 2014, unpublished observation]. In humans, promising results of the adjuvant use of PEA (combined with transpolydatin) have also been shown in the treatment of pain from endometriosis [13,28].

Down-regulation of mast cell activity thus appears a useful complementary approach to treatment of abdominal and pelvic pain of different origins.

Treatment of Pain Disease Interactions

Viscero-Visceral Interactions

In cases of suspected viscero-visceral hyperalgesia, treatment of one of the two visceral diseases has positive therapeutic repercussions on the other, as shown by clinical controlled studies [25]. Dietary treatment of IBS also relieves spontaneous and referred symptoms from dysmenorrhea and hormonal treatment of dysmenorrhea also relieves direct and referred intestinal pain/hyperalgesia in patients with IBS-dysmenorrhea co-morbidity. Similarly, stone expulsion promoted by extracorporeal shock-wave lithotripsy relieves dysmenorrhea symptoms and hormonal treatment of primary dysmenorrhea or laser treatment of endometriosis lesions in secondary dysmenorrhea also relieves urinary direct and referred pain symptoms in patients with dysmenorrhea and urinary calculosis comorbidity [25,27].

It is interesting to note that VVH also takes place when one of the two visceral diseases is latent with respect to spontaneous pain, e.g., women with silent endometriosis (i.e., endometriosis not giving rise to pelvic pain, discovered by chance at laparoscopy performed for infertility reasons) plus urinary calculosis present more urinary pain episodes and enhanced referred lumbar muscle hyperalgesia than women with calculosis only. In this case it has been shown that laser treatment of endometriosis produces a reduction of the urinary pain [25].

Viscero-Muscular Interactions

The relationship between myofascial trigger points and visceral pain is complex. On one hand a number of primary TrPs in abdominal and pelvic muscles, formed because of microtraumatic events, can give rise to pain mimicking visceral pain syndromes. It is the case of TrPs at various levels in the rectus abdominis, which can mimic the pain of dysmenorrhea or of appendicitis, or that of pain in the lateral abdominals, mimicking urinary pain [20,48].

On the other hand, visceral pain from various diseases of internal organs can produce the formation of secondary trigger points in the referred pain area, which can persist in time and be responsible for the persistence of the visceral-like pain even after the visceral focus has been eliminated. It has been shown, for instance, that 22% of patients with urinary calculosis who have spontaneously eliminated the stone still present colic-like symptoms and 88% of them still have residual lumbar muscle hyperalgesia 3 years after stone elimination. Physical examination of the referred area in these cases reveals the presence of trigger points, developed as a consequence of the visceral process, whose stimulation reproduces the typical visceral pain attack and whose extinction with local treatment reverts the visceral pain symptomatology. It has also been shown that 39% of patients with painful endometriosis who have been subjected to laser removal of lesions continue to experience spontaneous pain and 96% of them still present residual abdominal muscle hyperalgesia 1 year afterwards. Physical examination of the referred area in these cases reveals the presence of secondary trigger points whose stimulation reproduces the typical spontaneous pain and whose extinction with local treatment attenuates the visceral pain symptomatology [32,53].

Recent clinical studies have shown the implications for therapy of these viscero-muscular interactions in the case of multiple, though not contemporary, visceral pain syndromes in the same patient. The impact of previous urinary calculosis on pain from endometriosis has been investigated. It has been shown that women with endometriosis who had previously suffered from urinary colics from calculosis but had spontaneously eliminated the stone a long time prior to examination showed viscero-visceral hyperalgesia by presenting more painful menstrual cycles and referred muscle hyperalgesia from the uterus than women with dysmenorrhea from endometriosis without previous urinary calculosis. Physical examination in these women showed the presence of active TrPs in the lumbar region whose stimulation reproduced a colic-like pain. Local therapy of these TrPs was able to reduce the dysmenorrhea pain and also the referred hyperalgesia from the uterus in a prospective 6-month study. Other studies in women with urinary calculosis and previous endometriosis showed similar results. Women with recurrent urinary colics from calculosis who had previously suffered from endometriosis, subsequently cured by laser ablation of lesions, presented more numerous and intense urinary colics and more marked referred lumbar muscle hyperalgesia than women with calculosis only (i.e., without previous endometriosis). Physical examination of the rectus abdominis in the lower abdominal quadrants in co-morbid women showed the presence of active myofascial trigger points whose stimulation reproduced the typical uterine pain perceived at the time of active endometriosis. Local extinction of these TrPs with anesthetic injection produced a significant reduction of the urinary pain and of referred lumbar muscle hyperalgesia in a prospective 6-month study [Giamberardino et al, 2014, unpublished observation].

The presence of myofascial trigger points in a referred pain area from an internal organ can thus modify pain perception not only from that organ but also from other neuromerically connected organs [20].

Abdominal and Pelvic and Extra-Abdominal and Extra-Pelvic Interactions

Abdominal and pelvic pain occurring in the context of fibromyalgia [FS] or headache at a high frequency of crises (H) may significantly improve with effective specific pharmacologic prophylaxis of these conditions [17

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