(Da Lazzeri,Montorsi: Eur. Urol. 60(2011)78-80)
Currently, despite the multiplicity of research, the cascade of events that leads to the establishment of chronic cystitic disease has not been completely clarified, while the multiple so-called symptomatic therapeutic strategies usually fail or have only short-term effectiveness. In the majority of patients, the first cystitic manifestation can be traced back to an acute bacterial infection, although almost all researchers agree that this condition is probably the result of a primary defect in the urothelial lining.
While in the past the urothelium was considered a simple, albeit very sophisticated barrier, current studies have instead revealed both its sensitive function, with the possibility of informing the central nervous system of thermal, chemical or mechanical stimuli, and its efferent activity through the release of mediators that influence the contracting capacity of the smooth muscle cells of the bladder wall.
The ability of this barrier to maintain its protective role intact depends on the presence of GAGs (glucosaminoglycan) which cover its most superficial cells with a "mucinous" layer. The GAG has a multiplicity of functions and not only behaves as a "physical" barrier, but also functions as an anti-adherent factor and as a defense mechanism against infections and irritants (e.g. alcohol, chilli pepper, etc.).
The causes that can cause the decrease or loss of GAGs are, as mentioned above, multiple and not all of them have yet been highlighted. Repeated chronic infections certainly play an important role, but also particularly aggressive substances or chemotherapy or ionizing radiation administered for therapeutic reasons. Recent research has highlighted, in patients allergic to Nickel, the possible decrease in bladder defenses, with an increase in urinary infections. In these patients, the co-presence of vaginal candidiasis, cold sores and respiratory tract infections was statistically significant.
From the above, it is understandable how a decrease or a "hole" in the mucinous barrier of GAGs triggers damage to the underlying bladder wall with chronic neurogenic inflammation.
In fact, in this situation the toxic or rather "aggressive" substances, physiologically present in the urine, come into contact with a defenseless urothelium causing the activation of pro-inflammatory substances (such as substance P, neurokinins, bradykinin etc. ) which both maintain inflammation and activate the contraction of the bladder muscles.
A vicious circle is thus activated in which the release of these neuropeptides causes alterations in urination (urgent urge, very frequent urination) associated with pain, which is followed by a further reactive release of pro-inflammatory substances (substance P bradykinins etc.) which, in addition to regulate the contraction of the smooth bladder muscles, determine the migration of the cells of the immune system, the degranulation of mast cells (which in turn also release pro-inflammatory substances). All these mechanisms ultimately cause the onset of chronic neuritis.
In fact, when the defect of the GAGs persists or its repair process fails, the chronic stimulation of the suburothelial tissues causes a hypersensitivity of the bladder with the appearance of the so-called allodynia (i.e. pain from a stimulus that is normally not capable of causing it).
For example, the physiological sensation of bladder filling, necessary in the normal subject to inform the brain about the need to urinate, transforms into a sensation of burning pain, even very intense, which forces the patient to urinate very frequently which in turn causes further inflammation .
But in these cases, the damage caused by chronic inflammation is not only localized at the bladder level. In fact, the release of neuropeptides at the bladder level causes in a fairly short time the selection of a specific gene which at the level of the spinal cord increases the number of medullary synapses which, at this point, without the need for new algogenic stimuli, are able to cause and maintain increased hypersensitivity.
Let's remember that the painful signal in normal situations is carried to the brain where it is processed by the limbic system which we can roughly consider as the central management of emotions. When these messages arrive, behaviors are physiologically activated to interrupt this pain or prevent it from happening again.
However, if these signals are continuously repeated, as happens in chronic pain, the limbic system will first cause manifestations of anxiety and then gradually, as the pain persists, manifestations of anguish up to panic. At this point, radical changes in mood may sometimes occur, leading to a state of continuous depression.
Research on animals and humans has shown that in the depressive phase our ability to interpret pain decreases, resulting in a lowering of the pain threshold. The patient will then put continuous spasmodic attention to her symptoms at the center of her life, which for many of them, in the most serious cases, become a "reason" for existing.
In fact, when pain, from a physiological reaction to a nociceptive situation, becomes neuropathic, attention to it is a fundamental component. This is why this type of pain "inexplicably" decreases until it disappears during the night and instead increases when the patient's attention is not necessarily directed to other important commitments. Hence the common increase in pain on weekends and even more so during any "monotonous" holidays.
In the most suffering patients, all socializing interests will gradually be lost, with a negative impact also on inter-family relationships. This will naturally also depend on the sensitivity of the potential partner, who, despite all the good will, is usually unable to realize the drama experienced by his partner in the slightest. Partners often do not understand how intimacy as a couple could have suddenly been lost and will experience the denial of sexual relations (a frequent cause of painful stimuli) as an inexplicable and unjustified fault to be attributed to the partner.
From all of the above, it follows the need to intervene as soon as possible on the primitive local factors of inflammation, before these in turn, as explained above, release substances that stimulate the growth of the medullary neurosynapses.