Pain and endometriosis: How to optimize the medical management?

Transcription

1 Pre-congress course Endometriosis sand pelvic pain 1st Society for endometriosis and uterine Disorders Meeting Paris, 7-9 May 2015 Pain and endometriosis: How to optimize the medical management? J. FAIDHERBE Montpellier

2 Good News: Endometriosis is well healing when the removal of lesions is well done. Fortunately, it is the most frequent. You treat the cause and the pain disappears in 9 out of 10 Organ-centered Pathology

3 Bad news: Although the removal of lesions is well done, the pain persists, lingers.. urinary disorders urethral syndrome Pelvic myofascial syndrome Chronic Pelvic Pain and endometriosis irritable bowel Vulvodynia Vestibulodynia Proctologic painful syndrome Dysmenorrhea

4 The management of chronic pelvic pain has changed in gynecology since the discovery of the concept of central and peripheral hypersensitization Chronic Pelvic Pain is better understood thanks to the experimental model of endo-rat that has been discovered by K. BERKLEY Nociceptive pain Processing in CNS Memory of pain after removal of the lesion

5 Brain Function in women with CPP The use of imaging techniques to investigate organ structure is key in clinical practice in gynecology. However, over recent decades the use of functional imaging techniques, particulary neuroimaging, has become widespread In CPP, the focus is shift away from the pelvis and on to the CNS It can be seen that women with CCP do exhibit central changes Pelvic chronic pain, regardless of cause, is associated with alterations in brain function, particularly with regard to the processing of pain and other sensory information

6 Neuroimaging and the response to experimental pain BEHAVIORAL STUDIES NEUROIMAGING STUDIES One way to investigate the processes involved in pain perception is to evaluate the response to an experimental noxious stimulus. In (behavioral) studies, variety of different responses to the stimulus can be measured depending on the aims/design of the study. For example, in psychophysical studies, it is the patient s report of pain (usually on a visual analogue scale or a numerical rating scale) that is assessed. Whilst, neuroimaging studies combine such data with an objective measurement of brain activity in response to the stimulus. This allows insights into the central processes involved in pain perception and allows comparison between patients and healthy pain-free controls.

7 The notion of hypersensitization Eric Kandel works are major in the understanding of memory in lifescience

8 Endometriosis is an enigmatic painful disorder A rat model (endo) involves autotransplanting on abdominal cavity segments that grow into vascularized cysts that become innerved with sensory and sympathic fibers. Endo rats exhibit vaginal hyperalgesia

9 Experimental model of endometriosis used to explain a system of crossviscero visceral interactions Group 1: Endo: endometrial implants transplants Groupe 2: ShamEndo: fictitious (fat) implants transplants Groupe 3: Control group without surgical implants

10 Works of Karen J. Berkley and Pamella STRATTON 2010 Experience of pain is determined by the central nervous system. In pelvic organs, sensory fibers sprout new axons. Theses new axons become sensitized. The extend of sensitization is modulated by the association of estradiol and sympathetic-sensory coupling. And you have an extend of sensitization in the other parts of central nervous system, which is increasing with noxious stimulus.

11 Peripheric sensitization On laparoscopic view, the deeply infiltrating lesion on the left uterosacral ligament is expanded in the inset. Sensory fibers that sprouted new axons become sensitized. The extend of sensitization is dynamically-modulated by estradiol and sympathetic-sensory coupling Peripheral Nociceptors Primary sensory neurons

12 Central sensitization The CNS can retain a memory of central neuronal changes induced by the neural input. Remote central sensitization can also occur via longranging peripheral sensory fibers from disparate parts of the body and enormous CNS connectivity Central actions can become independent of any peripheral input from ectopic growths due to longterm modification of CNS functioning. All central effects can be modulated by estradiol. recalled by estradiol actions on activity of CNS neurons Pain would involve not only direct association with innerved pelvic organs but also with referred organs ( abdomino-pelvic muscles, bladder and colon.) Most central sensitization occurs at the spinal entry region of sensitized peripheral afferent fibers. Mostly in the pelvis because most lesions are located there.

13 Processing of nociceptive input in CNS RMI investigations Pathways in central nervous system C fibers, Aδ fibers of the posterior horn Nociceptive drive

14 Volumetric changes in grey matter in hypersensitization Chronic pelvic pain is associated with increased grey matter Compared with healthy painfree controls.

15 CPP, have significant central changes compared with healthy pain-free women Disparity between the extend of the disease observed at laparoscopy and the pain experienced (Vercellini et al., 2007) and the persistence of pain despite adequate surgical treatment. The pelvis and neuropathic pain is the consequence to damage of pelvic nerves during surgery or of the new nerves directly infiltrating the lesions (Stratton and Berkley, 2011).

16 EARLY LAPAROSCOPY IS IMPORTANT FOR A GOOD MANAGEMENT OF ENDOMETRIOSIS How to optimize the medical management in endometriosis? The diagnosis must be precise: key role of laparoscopy despite advances in imaging The laparoscopy must be performed at the right time: - Too soon, it would lead, for example, to perform a laparoscopy in a young patient with dysmenorrhea, which has no endometriosis - Too late, because the pain is on an authentic organic inflammatory and painful endometriosis with the risk of permanent anchorage of pain. Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis 212 Stacy L. McAllister., Natalia Dmitrieva., Karen J. Berkley*

17 Lag time between onset of symptoms and diagnosis Developing strategies for earlier diagnostic of endometriosis It would be important to reinforce the urgency of developing strategies for earlier diagnosis of endometriosis. K. Berkley studies clearly put an emphasis on prevention. This painful conditions involve direct damage to peripheral or central neural structures. It has been argued that visceral C-fibers that are sensitized in association with the initial inflammation of endometriosis may become a source of neuropathic pain. Early laparoscopy must be performed when you have suggestive symptoms.

18 Medical questionnaire in endometriosis must investigate the pain to emphasize the sensitization When you are looking for Hypersensitivity You can seek why surgery appears to be successful in some cases but less than successful in others, and what cautionary indicators should be taken into account Quantitative sensory tools have been developed to quantify different aspects of central sensitization Medical record should be oriented on hyper sensitization (Henrik Kehlet, Troels S Jensen, Clifford J Woolf, Persistent postsurgical pain: risk factors and prevention, The Lancet, Volume 367, Issue 9522, May 2006.)

19 NEW therapies of pelvic chronic pain Glial cells Hyperalgesic priming New therapies on nociceptive system Failure of classic Pelvic pain therapy: (NSAID, opioids, drugs reducing neuronal excitability..) Pain research have to clarify the neuronal mechanisms which are involved in the generation and maintenance of pain (Spinal sensitization involvement of neurons and glial cells Peripheral sensitization and hyperalgesic priming ) New therapies have to be developed on peripheral nociceptive system, and on central nociceptive system (nociceptive neurons in the spinal cord, nociceptive neurons in thalamocortical system)

20 Conclusions EARLY LAPAROSCOPY IS IMPORTANT Medical record have to emphasize the sensitization New therapies have to be developed on peripheral nociceptive system, and on central nociceptive system