Sympathetic nervous system and chronic bladder pain: a new tune for an old song

Abstract

Chronic bladder pain (CBP) patients present with pelvic pain or discomfort during bladder filling, for at least a period of 6 months, which may be accompanied by lower urinary tract symptoms such as frequency, nocturia, and urgency. However, both the etiology of CBP and pathophysiological mechanisms are not well described. A number of clinical and basic animal model findings support involvement of sympathetic nervous system in chronic pain syndromes such as CBP. Examples include sympathetic overactivity and high plasma or urinary catecholamine levels that have a high correlation with nociceptive symptoms. In this review, we explored the current evidence in support of the involvement of sympathetic overactivity in CBP. As bladder inflammation often occurs among subgroups of CBP patients, we discuss the possible role of sympathetic nervous system in mastocytosis as well examples examples of animal models that further support the involvement of sympathetic dysfunction in CBP. As there is substantive evidence for cross-organ sensitization in the pelvis can lead to co-morbidity of genitourinary and gastrointestinal dysfunctions, we also include how sympathetic dysfunction may play a role in a number of co-morbid chronic pain syndromes.

Keywords: Chronic bladder pain (CBP); nociceptors; stress; sympathetic nervous system.

Figure 1

Graph bar showing the mean values of the variation of the standard deviation of the P wave interval of healthy subjects (control) and patients with chronic bladder pain (CBP). Adapted from Charrua et al. [2015] (5).

Figure 2

Graph showing a significant correlation between the percentage of decrease of pain intensity (%∆VAS; if more than two) and the percentage of decrease of urinary noradrenaline (%∆Noradrenaline), at 1-month follow-up (n=16).

Figure 3

Graph bar showing mean values of number of mast cell infiltration per square millimetre of urinary bladder mucosa. Animals subcutaneously receiving 2.5 mg of PHE per kg of body weight (PHE 2.5 mg/kg, n=4), for 14 days, presented more mast cells than control animals (**, P<0.01, n=4). Pre-treatment with 75 mg CAP before the PHE treatment (PHE 2.5 mg/kg + CAP, n=4) reverse the PHE induced mast cell infiltration. PHE, phenylephrine; CAP, capsaicin; *, P<0.05.