Myths about endometriosis: pain isn't related to location of deposits

[kaberett]

It's very true, to be clear, that pain and infertility and extent of deposits are not well-correlated. (This is partly because the standard grading of endometriosis arises from likely impact on fertility, rather than from any other functional outcomes - so one can be infertile with "severe" endometriosis and have very little pain, or have "mild" endometriosis with severe pain.)

HOWEVER. This does not mean that pain is never related to location and extent of endometrial deposits. Unsurprisingly, I've been doing some reading on this today (fuck the establishment, man), focussing on deeply-infiltrating endometriosis, because that's what I have. (I swear, one of these days I'm going to get pissed off enough - and have enough spare time - that I'm going to do a proper literature review, then send it off to my gynae consultant and see if he's interested in a joint publication.)

• "The types of pelvic pain are related to the anatomic location of DIE. Knowledge of the characteristics of pelvic pain symptoms is important in the preoperative assessment of patients with suspected DIE." Fauconnier et al, 2002.
  
• Anaf et al., 2006: "The presence of increased activated and degranulating mast cells in deeply infiltrating endometriosis, which are the most painful lesions, and the close histological relationship between mast cells and nerves strongly suggest that mast cells could contribute to the development of pain and hyperalgesia in endometriosis, possibly by a direct effect on nerve structures."
  
• Vercellini et al. (2007) conclude "The association between endometriosis stage and severity of pelvic symptoms was marginal and inconsistent and could be demonstrated only with a major increase in study power" -- BUT also say that "the only strong association observed by most investigators is between deep posterior cul-de-sac lesions and dyspareunia [painful sexual intercourse [...] confirm[ing] the 'organic' nature of the symptom," and that "deep endometriotic lesions may be neurotrophic, as they have been consistently associated with higher expression of nerve growth factor in comparison with peritoneal and ovarian implants." Further: "The only strong association observed with regard to implant characteristics both at general and subgroup analysis was between pouch of Douglas lesions and deep dyspareunia. As the correlation between ‘deep’ disease of the posterio-uterine cul-de-sac and severe pain is consistent in almost all studies that addressed the issue." And: "More likely, the intensity of pain is determined not by the type and extension of implants per se but by the interaction between endometriotic lesions and sensory afferent nerve fibres (Vercellini 1997; Anaf et al., 2000), a variable that does not follow predictable patterns."
  
• "Definitive criteria determining which, if any, endometriosis lesions cause pain symptoms are lacking. In carefully documented studies, location and extent of lesions bear little relation to location or amount of pain a woman experiences (Vercellini et al., 1996, 2007; Parazzini et al., 2001; Chapron et al., 2003; Fauconnier and Chapron, 2005). All three lesion types are associated with CPP, including those women with only minimal or mild endometriosis using the American Society for Reproductive Medicine (ASRM) classification (Fauconnier and Chapron, 2005). [...] DIE lesions are the only ones that are consistently associated with CPP (Fauconnier and Chapron, 2005). Non-menstrual CPP and gastrointestinal symptoms occur at a higher rate in those with bowel DIE lesions and painful defecation during menses with DIE involving the vagina (Fauconnier et al., 2002). [...] The role of adhesions in pain and endometriosis is poorly understood (Rapkin, 1986; Parazzini et al., 2006; Vercellini et al., 2009b; Yeung et al., 2009)." They follow this up by examining evidence for innervation of the various types of endometrial deposit: "In clinical studies, using immunohistochemical techniques to mark various neuronal fiber types, Fraser's group demonstrated sensory, sympathetic and parasympathetic fibers in different types of lesions, reporting that innervation is denser in DIE than other lesion types, and densest in rectal DIE lesions (Tokushige et al., 2006b; Fraser et al., 2008; Wang et al., 2009). Importantly, Mechsner et al. (2009) found that nerve fiber density correlated with severity of pelvic pain or dysmenorrhea." Further, we get acknowledgment that location of DIE does seem to be tied to pain: "This incomplete assessment strategy hampers assessment of pain outcomes (Vincent et al., 2008) and fails to consider diagnostic subtypes of CPP (Leserman et al., 2006), such as those noted with different locations of DIE (Fauconnier et al., 2002)." (Stratton and Berkley, 2011.)
  

Where things go wrong is when people take paragraphs like this one, from Stratton & Berkley (2011), and determine that all endometriosis-associated pain arises from CNS activity and hyperstimulation/sensitivity of abdominal pain systems, with no link whatsoever to location and type of endometrial lesion:

Many factors can contribute interactively to individual variability in endometriosis-associated pain. Research so far encourages consideration of endometriosis as a chronic inflammatory disease, which, in turn, encourages a multi-therapeutic approach to its treatment (Table III). Furthermore, because pain of any type resides in nervous system activity, research also suggests that a major contributing factor for endometriosis-pain is not the ectopic growths themselves, but rather how sensory and autonomic nerve activity from nerves that have sprouted from nearby tissues to innervate the growths affect activity of neurons in the spinal cord and brain.

This doesn't map at all with my experiences. My endometriosis pain consists of:

• wide-spread pelvic aching/burning (background, chronic pain: this I believe to be associated with overactivity of pelvic nerves)
  
• infrequent stabbing, buzzing, or fizzing pains associated with my sciatic and genitofemoral nerves, exacerbated by but not confined to periods of motion/walking (I suspect this is related to endometriosis growth impinging on aforementioned nerves, as severity and frequency of this pain is characteristically progressive)
  
• ovary-related pain, and cyst-related pain (despite the finding that innervation of endometriomas is usually minimal, "holy FUCK that hurt" is a well-known reaction to bursting ovarian cysts, and I do get characteristic pain patterns associated with ovaries with known cysts in the run up to bursting - particularly, the pain is similar to the pain upon bursting)
  
• adhesion-related pain: tugging and burning associated with surgical incisions and known adhesive wossnames
  
• sharp burning pain very obviously localised to endometrial nodules in my rectovaginal septum (seriously, it's kind of hilariously awful when several of them set off at once)
  
• probably some more that I'm forgetting at the moment.
  

Key points

• of the three types of endometriosis (peritoneal, deeply-infiltrating, ovarian/cystic), DIE is the only one consistently associated with severe pain
  
• endometriosis-related pain appears to consist of both non-localised widespread pain not associable with specific deposits, and localised pain that can be well-correlated with (particularly DIE) deposits
  
• in patients with DIE, pain distributions pre-surgery can be a useful indicator of deposit distribution
  
• "we don't know why adhesions are painful for some people and not for others" does not mean "it's not adhesions causing your pain" (c.f. Mueller et al., 1995)
  
• in patients with DIE, it is entirely plausible for severe, localised pain to have a causal association with particular endometrial deposits, though in most cases it does not
  
• distribution of lesions does not generally correlate well with reported pain (i.e. many lesions are not associated with pain); however, no-one has demonstrated that specific localised pain isn't associated with specific lesions, and, er, I kind of demonstrate that kind of association
  

I suspect at least some of the confusion arises from the definition of "chronic pelvic pain": I completely believe that my widespread, burning, "background" pain has nothing to do with individual, identifiable lesions. However, my pain spikes - sharp, localised pain - is very different in character, and I suspect is frequently glossed over in these studies: I certainly didn't come across any explicit references to this type of pain.

In any case, I'm pretty comfortable saying that my pain doctor was wrong, and I am mentally composing an extremely polite letter to the tune of:

As discussed in our appointment, I feel much better equipped to manage my pain when I am well-informed about the related biological processes. To recap, I have widespread deeply-infiltrating endometriosis, with complete obliteration of the Pouch of Douglass and significant palpable nodules in my rectovaginal septum. During our conversation, you explained that my pain no longer had any relation to the physiological reality of location and distribution of my endometrial deposits. I'd really appreciate it if you could explain the apparent inconsistency between this statement and the findings of [HAVE A HUGE LIST OF REFERENCES :D].

I AM A DOUCHE.

Glossary
CNS: central nervous system
CPP: chronic pelvic pain
DIE: deeply-infiltrating endometriosis
dyspareunia: painful sexual intercourse

(NTS: Ford et al. 2004 are useful on the topic post-operative results of radical resection of rectovaginal endometriosis.)

Comments

[kaberett]

NB I am very aware that I am likely to be showing bias in my (cursory, brain-kinda-floaty) analysis of the literature, and am very open to being pulled up on that, but I think my basic point - that "endometriosis pain doesn't ever have anything to do with the actual distribution of endometriosis you have" is demonstrably false and not supported by the literature - does stand.

[liv]

It may well be that your pain doctor is just irredeemably crap. But if you're still trying to get good communication here, I think I might add a line about your personal experiences to your letter. As in, for your last sentence, something like:

I personally experience several forms of localized pain, as is consistent with the following literature on DIE specifically [long list of references]. I would appreciate if you could explain the inconsistency between your statement and both my personal experiences and the research literature on my condition.

I'm not suggesting this because I think you somehow omitted to mention your own history at the previous consultation, but because "my experience aligns with the literature" gets some otherwise oblivious medics to sit up and pay attention in a way that either "my experience is" or "the literature says" alone doesn't.

[kaberett]

Thank you :-)

If I do end up sending this letter, I will probably reframe it like that! I think it would probably be better to e-mail him than to just bring it up in consultation (because that way I can provide the papers and he can read them...)

I am also relieved that you don't think I've cherry-picked or misinterpreted egregiously ;)

[liv]

I haven't cross-checked your analysis of the literature, I just took your post here at face value. If you'd like me to do that I can but I'm very unlikely to get to it before the weekend; how time critical is this? Pain isn't my field so I'm probably only a little bit better than you able to judge whether you're interpreting and synthesizing correctly, I don't want to presume that it would be worth it for me to go over your lit search. But I also don't want to give the impression that by commenting I'm endorsing your conclusions when actually I'm just assuming you're right without checking.

[kaberett]

It's not something I need you to do, but if nothing in this post leapt out as OBVIOUSLY MISREPRESENTATIONAL then I'm cool with that ;)

[shehasathree]

Nicely done!

[ghoti]

Stupid question: painful /penetrative/sex or all kinds?

[kaberett]

WHAT IS THIS NON-PENETRATIVE SEX OF WHICH YOU SPEAK

[ghoti]

THE RUBBING GAY KIND

[kaberett]

by which I mean: afaict the medical establishment thinks that penetrative sex is the only kind that exists, but I have also had pain during non-penetrative sex (typically of slightly different character, except during orgasm).

[shehasathree]

This post is MADE OF AWESOME and I <3 the way your brain works.
(I mean, obviously I don't think it's awesome you're in heaps of pain. But intellectualisation is my preferred defense mechanism, knowledge is power etc etc.)

I'm guessing I'll finally get to find out if I have endo when I see a gynaecologist for the first time in about 5 weeks...

[kaberett]

Positive diagnoses are only possible with laparoscopic surgery, so maybe don't get your hopes up? :-/ But also GOOD LUCK.

[shehasathree]

Oh yeah, i keep forgetting that. Ugh. Don't really want surgery. But at least it'll be nice to have an opinion based on greater expertise and knowledge than "yeah, that sounds like it could be endo" and "your CT scan of your abdomen [to look at your Crohn's Disease] showed heaps of cysts on your ovaries, but I'm a gastroenterologist, so no comment or advice".

[bjh21.me.uk]

I'd really appreciate it if you could explain the apparent inconsistency between this statement and the findings of [HAVE A HUGE LIST OF REFERENCES :D].

I mention this because that's precisely the kind of thing I've got into trouble for: that kind of phrasing is liable to step across the line from deference into sarcasm. Better might be something more straightforward like, "Based on a review of the literature, I suspect this may not be true of my kind of endometriosis: [stuff]".

[ It's possible that this is either stating the obvious or wrong. That I can't tell which probably explains why my boss tries to keep me away from users. ]