Main Findings :
The existence of PUS by central sensitization, as defined above, which in particular causes severe dysmenorrhoea, appears increasingly plausible, regardless of whether endometriosis is present or not. Recent studies by Evans (43), Stratton (44), and Grundström (45) all point in this direction.
PUS or ”endometriosis-like” syndrome is typically identified by negative imaging and anatomical findings. The main symptom is severe dysmenorrhoea; however, pelvic pain from uterine contractions, deep dyspareunia, and uterus trigger pain at vaginal examination, are among the diagnostic criteria as defined in the PUS diagnostic score (Table 1).
The Viscero-Visceral sensitization mechanisms, as described by Giamberardino (46), account for a common association with painful bladder syndrome through peripheral sensitization phenomena. Similarly, co-morbidities such as hyperesthesia of the vulvar vestibule, are connected with the occurrence of the frequent Provoked Vulvar Vestibulodynia (PVD) (47), which is responsible for introductory dyspareunia.
But the most frequently associated disorders are pelvic floor muscle hypertonia and myofascial syndromes (42, 44). This muscle hypertonia is consistent with pelvic sensitization and, therefore, applies to PUS, which has been well documented in the various cine MRI studies, as described above.
In terms of therapeutic consequences, BTX injections have a logical application here. Besides its widely demonstrated effectiveness in treating muscle spasms, hypertonia, or hyperactivity by inhibiting the release of acetylcholine at the neuromuscular junction by competitive neurotoxin inhibition (48 and 49), BTX may also have direct peripheral and central analgesic effects. It may also have a direct effect on inflammation by reducing the release of pro-inflammatory neuropeptides (50 and 51)
The use of BTX in pelvic floor muscle hypertonia, spasms, and myofascial pain was first documented by Abbott in 2006 (52). Several publications have confirmed that botulinum toxin injections are useful for treating this condition (53, 54, 55, 57, and 58). The effectiveness of BTX injections on pelvic floor muscle hypertonia and spasms has been proven in a number of prospective and randomised studies (54 & 57). On the other hand, for myofascial pain, the randomised studies conducted by Dessie (59) and Levesque (60) found no significant difference with the control group for saline and local anaesthetics, respectively.
As far as we know, uterine myometrial BTX injections used in cases of PUS and/or severe dysmenorrhoea has never been described before. This indication follows the same pathophysiological approach as that proposed for OAB or PBS (31, 32 & 33).
The procedure under hysteroscopy is simple and can be easily reproduced. Our pilot study (34), mentioned above, reported no immediate or remote post-operative complications.
Although pregnancy was not recommended within 4 months of the myometrial injection in this study, no maternal or fetal complications were reported in the literature when a botulinum toxin injection was administered during pregnancy (61 & 62). One patient in our study became pregnant, despite being advised against it. This was an unintended pregnancy and a voluntary termination was performed in the first trimester. This procedure was carried out without any complications.