IC and the Autonomic Nervous System
The topic I wanted to dive further into, which will be ongoing for me, is the correlation to the autonomic nervous system (ANS) and interstitial cystitis (IC), painful bladder syndrome (PBS) and chronic bladder pain (CBP). IC and other bladder conditions is proposed to have causes such as infection, autoimmunity, toxic substances in the urine and psychological causes (Zeybek et al., 2007). The morphological criteria for IC include mononuclear inflammation, mucosal hemorrhage, deficiencies in the mucosal layer of the bladder, epithelial disruption in the mucous layer of the bladder, and epithelial disruption and increased mast cells in the urothelium (Zeybek et al., 2007). Patients with these disorders present with pelvic pain or discomfort during bladder filling, for a period of at least 6 months, often accompanied with urinary tract symptoms such as frequency, nocturia, and urgency. One of my clients asked me “how can I heal my autonomic nervous system?” I have to be honest, it was a new area for me toe explore, so the timing of this course was appropriate. I really liked the material Regalla collaborated for this course. According to Regalla, the autonomic nervous system consists of select parts of the central nervous system (CNS) and peripheral nervous system, and I believe these are a huge piece to the etiology of IC. The ANS regulates housekeeping functions of the body such as regulating temperature, heart rate, respiration, blood pressure and smooth muscles and glands inside our body. The sympathetic nervous system regulates blood pressure and norepinephrine is the messenger; the parasympathetic nervous system activates the heart rate, promotes urination and intestinal defecation and acetylcholine (ACH) is the messenger.
What was interesting to me is the characteristics of autonomic dysfunction among the IC population. For example, dysregulation of the adrenomedullary hormone system (AHS), can lead to high or low blood pressure, postural hypotension or orthostatic intolerance (OI). OI is a sudden drop in blood pressure when an individual stands up from a sitting, squatting, or supine position. I used to recall having a pretty severe case of OI, and in some circumstances, I lost my balance or fainted! I also have always had pretty low blood pressure, 95/60, and so do many of my clients. The second form of OI that some of my clients complain about is postural tachycardia syndrome (POTS) which is a form of OI where their heart rate will increase without fainting. I believe I also experienced this at some points in my life as well. “Consequences include symptoms such as fragile blood pressure, high blood pressure, orthostatic intolerance, low blood pressure, low pulse rate, fainting, and cardiac arrhythmias, anxiety, and a sense of being wired and tired” (Regalla, n.d). Many people with IC also suffer from various forms of adrenal dysfunction, as evidenced when we run Dutch hormone tests. I often see low overall cortisol, sometimes high metabolized cortisol (due to high stress) but low free cortisol. In addition, the symptoms often represented in the adrenal fatigue setting include fasting than normal heart rate at rest, anxiety, feeling wired but tired, heart palpitations at rest, fragile blood pressure, insomnia, dizziness, and low blood sugar (Regalla, n.d.). “It is likely that such ANS dysfunction is triggered by AHS activation as a compensatory response to adrenal fatigue. Thus, dysfunction of the ANS is secondary in nature” (Regalla,n.d.). However, since some clients will demonstrate normal to high blood pressure with faster heart rates, blood pressure alone is not an accurate gauge of the overall clinical picture without consideration of the detailed history of the patient. Dysfunction of the ANS is called dysautonomia, which can be either primary or secondary, clinical or sub-clinical. All presentations of ANS involve the mind and body because every emotion a person feels includes some body function through the ANS. This makes IC very much a mind-body disorder, and a crucial area that needs to be addressed in every IC healing program.
What does the literature say?
I wanted to take this opportunity to review some things I found in literature about this topic. To date, several studies have assessed various aspects of the ANS in a variety of painful disorders. Some examples include heart rate variability in fibromyalgia or irritable bowel syndrome or heart rate and blood pressure change to bladder filling in IC/PBS (Chelimsky et al., 2012). Interesting, the current findings indicate that ANS structure in these patients does not differ from that of healthy matched females with IC/PBS, suggesting that observed ANS differences more likely relate to functional, not structural abnormalities (Chelimsky et al., 2012). “ The observed increase in the baseline heart rate, as well as a trend for increased heart rate after 10 min upright, support a tentative conclusion of an abnormality in ANS responsiveness and function, rather than any structural change in the autonomic fibers or connections themselves” (Chelimsky et al., 2012). The issue is, studies on the role of ANS in patients with IC/PBS are scarce. However, the few that exist demonstrate increased heart rate variability, and in some cases, increased baseline heart rate at rest compared to healthy controls. Heart rate variability is defined as the difference in duration between successive heartbeats, measuring the autonomic nervous system’s ability to modify heart rate in response to neurophysiological changes (Williams et al., 2015). The heart rate in healthy humans is influenced by physical, emotional, and cognitive activities, and physiological oscillations that lead to variable beat-to-beat fluctuations in HR is known as HRV (Tyagi & Cohen, 2016). In addition, there has been evidence of increased resting diastolic blood pressure as well as increased anxiety in patients with IC/PBS. Therefore, it seems plausible that there is an abnormality of sympathetic/parasympathetic balance rather than a structural change in the ANS function of these patients. These findings require confirmation with a larger cohort, but suggest that ANS structure is not different in subjects with IC/BPS when compared to highly screened healthy subjects.
A number of clinical and basic animal model findings support involvement of sympathetic nervous system as well in chronic pain syndromes involving the bladder. Sympathetic overactivity is evidenced by increased plasma or urinary catecholamine levels that are correlated with painful perceptions (nociceptive symptoms) (Charrua, Pinto, Birder, & Cruz, 2015). Bladder inflammation is also involved in some subgroups of patients with PBS, which is theorized to be due to the possible role of mastocytosis with the sympathetic nervous system. “Typical pathological findings include bladder inflammation, mast cell accumulation in the bladder wall and urothelial thinning or disruption” (Charrua et al., 2015).
It is not to say there are no morphological changes in the urothelium. Often times changes such as urothelial thinning, decreased urothelial cell cohesion and loss of the GAG layer leads to the common belief that the condition is linked to increased permeability of the urothelium. The increased permeability can potentially contribute to diffusion of urine constituents into the bladder wall which can induce inflammation, mast cell accumulation and activation of nociceptive fibers (Charrua et al., 2015). “The leaky urothelium, whatever the cause, is expected to self-perpetuate bladder inflammation and nociceptive fibers activation” (Charrua et al., 2015). Exposure to various forms of stress can induce mast cell proliferation and activation, with urothelial damage to the bladder (Zeybek et al., 2007). Mast cells release inflammatory mediators such as histamine, proteases, prostaglandins, leukotrienes and cytokines.
In addition, IC/PBS is often associated with other painful conditions such as fibromyalgia, IBS and CFS, which is theorized to also involve the sympathetic nervous system. Williams et al (2015) indicated that 60% of IC patients have greater sympathetic tone and greater reactivity to stress than healthy controls. They report increased symptoms during stress. “The stress response involves physiological adaptation to stimuli perceived as physically or emotionally threatening with activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis, immune system and various other physiologic and psychological effects (Williams et al., 2015)”. Findings are consistent with reports of increased symptoms, pain and urgency with voiding by acute mental stressors, which are associated with the sympathetic effects on the inflammatory processes in IC patients that has been documented (Williams et al., 2015).
What can you do about it?
Interestingly, there are ways to ameliorate stress induced physiological responses of the urinary bladder, which is an area I would like to research in more depth. One that I have always coached my client with is in regards to exercise, particularly yoga. Yoga practices, including meditation, relaxation, yoga postures, breathing, and integrated practices, appear to improve autonomic regulation and enhance vagal dominance as reflected by HRV measures (Tyagi & Cohen, 2016).” Although the mechanism by which yoga influences autonomic activity is not well understood, some yoga practices appear to directly stimulate the vagus nerve and enhance parasympathetic output leading to parasympathetic dominance and enhanced cardiac function, mood, and energy states, as well as enhanced neuroendocrine, metabolic, cognitive, and immune responses”(Tyagi & Cohen, 2016). Interestingly, the bidirectional flow of the vagus nerve can allow for interactions between areas of the brain such as the amygdala, prefrontal cortex, and the peripheral organs as well as mediating cognitive and emotional responses as well. “Heart rate variability, therefore, appears well placed to reflect the emotional and cognitive influences on organ function and the mind-body integration that occurs with many yoga practices by directly linking the input and output of the central nervous system” (Tyagi & Cohen, 2016). It should be pointed out that some yoga practices can increase heart rate while some meditation associated with slow breathing can lower heart rate. “This may be due to slow breathing being an active process that is associated with heightened attention and an increased metabolic rate while meditation is a passive practice that is associated with diminished attention and reduced metabolic rate” (Tyagi & Cohen, 2016). The ability of yoga to influence autonomic function has been the subject of numerous studies that suggest that yoga practices reduce autonomic arousal and assist with a wide range of stress-related disorders. Yoga practices have also been reported to reduce anxiety and induce relaxation. While at least some of the stress-relieving effects of yoga may be related to altered autonomic arousal, clinical improvements with yoga are not necessarily reflected by changes in HRV. For example, yoga practices are reported to reduce HR, without corresponding changes in HRV. Improvements in quality of life, flexibility, and mood with various yoga practices are also reported despite no change in HRV. “It may be that many of the positive effects of yoga on autonomic function are due to resonance effects produced by changes in respiration or by other mechanism such as rhythmical skeletal muscle tension occurring during various yoga postures that may lead to vagal dominance and enhanced baroreflex gain without corresponding changes in HRV”(Tyagi & Cohen, 2016). As I continue to research this topic, I will post further updates on opportunities to improve autonomic function in the hopes of future therapies for IC healing.
Charrua, A., Pinto, R., Birder, L. A., & Cruz, F. (2015). Sympathetic nervous system and chronic bladder pain: a new tune for an old song. Transl Androl Urol, 4(5), 534-542. doi:10.3978/j.issn.2223-4683.2015.09.06
Chelimsky, G., Heller, E., Buffington, C. A., Rackley, R., Zhang, D., & Chelimsky, T. (2012). Co-morbidities of interstitial cystitis. Front Neurosci, 6, 114. doi:10.3389/fnins.2012.00114
Regalla, S. (n.d.) Adrenal Fatigue & Blood Pressure. [Lecture] Retrieved (2019, January 8) from file:///C:/Users/Matt%20Heagle/Downloads/MUIH%20NUTR%20835%20Wk%202%20Adrenal%20Stress%20and%20BP%20(2).pdf
Tyagi, A., & Cohen, M. (2016). Yoga and heart rate variability: A comprehensive review of the literature. Int J Yoga, 9(2), 97-113. doi:10.4103/0973-6131.183712
Williams, D. P., Chelimsky, G., McCabe, N. P., Koenig, J., Singh, P., Janata, J., . . . Chelimsky, T. (2015). Effects of Chronic Pelvic Pain on Heart Rate Variability in Women. J Urol, 194(5), 1289-1294. doi:10.1016/j.juro.2015.04.101
Zeybek, A., Saglam, B., Cikler, E., Cetinel, S., Ercan, F., & Sener, G. (2007). Taurine ameliorates stress-induced degeneration of the urinary bladder. Acta Histochem, 109(3), 208-214. doi:10.1016/j.acthis.2006.12.001