Central changes associated with chronic pelvic pain and endometriosis

In the paper

“However, these findings are not consistent, as not all studies observed an increase in all measures of the pain experience”

• Also stated in: § Behavioural responses to experimental pain in women with CPP · plain

  “whilst some studies did not observe any heightened response in women with CPP”

What the sources say

• Not checked yetcites Wilder-Smith et al., 2004
• Not checked yetcites Ringel et al., 2008

In the paper

“In the first, pressure stimulation of the vulva elicited activation of similar pain regions between women with provoked vestibulodynia and healthy controls; however, the women with provoked vestibulodynia demonstrated significantly stronger activation in several of these regions”

What the sources say

• Not checked yetcites Pukall et al., 2005

In the paper

“As before, however, these findings are not consistent in all reported studies (see Supplementary data, Table SIII) including one study that found no differences; however, it only investigated regions within the cingulate cortex”

What the sources say

• Not checked yetcites Ringel et al., 2008

In the paper

“In response to painful distension of the sigmoid colon and rectum, individuals with IBS have demonstrated decreases in parasympathetic and increases in sympathetic nervous system activity when compared with healthy controls (although this finding was only significant in men with IBS)”

What the sources say

• Not checked yetcites Tillisch et al., 2005

In the paper

“Thus, abnormally low cortisol levels have been observed in women with endometriosis and CPP (Petrelluzzi et al., 2008), dysmenorrhoea (Vincent et al., 2011) and provoked vulvodynia (Ehrstrom et al., 2009) and replicated over repeated measurements”

What the sources say

• Not checked yetcites Petrelluzzi et al., 2008
• Not checked yetcites Vincent et al., 2011
• Not checked yetcites Ehrstrom et al., 2009

In the paper

“Although these increases were observed in different brain regions from those where reductions in volume have been observed in other conditions, these regions are also known to be involved in the processing of noxious stimuli.”

In the paper

“Interestingly, although decreases in grey matter were observed in many pain processing regions, areas with an increased volume were also observed”

What the sources say

• Not checked yetcites Schweinhardt et al., 2008
• Not checked yetcites Blankstein et al., 2010
• Not checked yetcites Seminowicz et al., 2010

In the paper

“In women with endometriosis, the circadian pattern of cortisol secretion was maintained but suppression of cortisol secretion occurred throughout the day”

What the sources say

• Not checked yetcites Petrelluzzi et al., 2008

In the paper

“Thus even women who only suffer with dysmenorrhoea (as opposed to pain throughout the month) have increased tendencies for depression and anxiety (Dorn et al., 2009), although this is not a universal finding (Vincent et al., 2011).”

What the sources say

• Not checked yetcites Dorn et al., 2009
• Not checked yetcites Vincent et al., 2011

In the paper

“Similarly, women with endometriosis (Sepulcri Rde and do Amaral, 2009; Smorgick et al., 2013) and provoked vestibulodynia (Nunns and Mandal, 1997) are more likely to have anxiety or depression, but may otherwise be psychologically healthy”

What the sources say

• Not checked yetcites Sepulcri Rde and do Amaral, 2009
• Not checked yetcites Smorgick et al., 2013
• Not checked yetcites Nunns and Mandal, 1997

In the paper

“Whilst this was once considered a fixed matrix, it is now known to be dynamic and dependent on various factors, such that the regions involved will vary, essentially producing a ‘cerebral signature’ of pain”

What the sources say

• Not checked yetcites Tracey and Mantyh (2007)

In the paper

“it does not appear to be purely a reflection of the presence of ongoing pain, as women with dysmenorrhoea demonstrated enhanced behavioural responses to noxious stimulation of both the abdomen and arm throughout the menstrual cycle and not just at the time they were experiencing pain”

What the sources say

• Not checked yetcites Vincent et al., 2011

In the paper

“Moreover, the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions.”

In the paper

“The amplification within these regions might be due to compromised spinal and/or brainstem pain modulatory circuits in the patient cohort, since neural activity often differed by magnitude, not just brain region.”

In the paper

“Furthermore, even when pathology is identified and treated the pain may still persist, suggesting that the pathology was either an incidental finding or that other mechanisms continue to generate pain without the need for a peripheral input”

What the sources say

• Not checked yetcites Baranowski, 2009

In the paper

“Some of the findings described above and in Supplementary data, Table SIII may represent abnormal pain inhibition, as many of the studies identify changes in the prefrontal cortices, amygdala and insula, which are key regions of the descending pain inhibitory system.”

In the paper

“DNIC is a mechanism by which painful stimuli to one location decreases perceived pain elicited by noxious stimuli at a distant part of the body”

What the sources say

• Not checked yetcites McMahon (2013)

In the paper

“it has even been suggested that the inability to engage these systems may predispose to the development of chronic pain after an acute insult”

What the sources say

• Not checked yetcites De Felice et al., 2011

In the paper

“there is a network of brain regions that responds to a noxious stimulus and therefore may contribute to the generation of the experience of pain”

What the sources say

• Not checked yetcites Tracey and Mantyh (2007)

In the paper

“It is possible that methodological differences in these studies (inclusion criteria, differing experimental pain techniques, methods for determining pain thresholds, pain rating protocols, number of study visits, and sample sizes) contributed to this inconsistency”

In the paper

“It is well established that endogenous central pain inhibitory mechanisms exist, mediated through a variety of spinal and cortical mechanisms”

What the sources say

• Not checked yetcites McMahon (2013)

In the paper

“Firstly, the autonomic symptom profile included symptoms relating to bowel and bladder function yet ten of the fifteen CPP patients had pain with a full bladder and/or with bowel movement.”

In the paper

“cortisol, as one of the principal players in the HPA axis, appears to be central to the phenomenon of stress-induced analgesia (Filaretov et al., 1996) and therefore a reduction in cortisol levels secondary to dysfunction of the HPA axis may exacerbate pain.”

What the sources say

• Not checked yetcites Filaretov et al., 1996

In the paper

“Secondly, there was no assessment of drug use in the CPP cohort and, as the authors describe, many of the autonomic symptoms may be secondary to the drugs prescribed to treat their pain.”

In the paper

“The mechanisms behind these alterations in brain volume are not completely understood but may include a direct neurotoxic effect of repeated episodes of pain leading to neuronal atrophy or death, an effect of altered metabolic activity or neurotransmitter concentration, neurotoxic effects of drugs, neurodegeneration secondary to pain-related inactivity, and an effect related to psychological”

What the sources say

• Not checked yetcites May, 2008
• Not checked yetcites May, 2011

In the paper

“The authors suggest that this may be due to the PAG’s role in descending pain inhibition and potentially may explain why some women with endometriosis have little or no pain despite a significant burden of disease.”

In the paper

“The mechanism(s) by which suppression of the HPA axis is produced are as yet unclear.”

In the paper

“Burnout of the system has been proposed as one possibility (Hellhammer and Wade, 1993; Fries et al., 2005) and the recent finding that cortisol levels were negatively correlated with the duration of dysmenorrhoea (Vincent et al., 2011) would be consistent with this, suggesting that HPA axis suppression is a consequence not a cause of their symptoms.”

What the sources say

• Not checked yetcites Hellhammer and Wade, 1993
• Not checked yetcites Fries et al., 2005
• Not checked yetcites Vincent et al., 2011

In the paper

“In view of the negative impact of chronic stress on important physiological processes including the immune system and memory function”

What the sources say

• Not checked yetcites McEwen, 2005

In the paper

“it has been proposed that suppression of HPA axis activity might in fact be a protective mechanism”

What the sources say

• Not checked yetcites Fries et al., 2005

In the paper

“The volume of the grey matter in the anterior cingulate cortex is reduced in almost all these conditions; however, reductions are also commonly seen in the volume of other regions particularly the thalamus, insula and prefrontal cortices”

What the sources say

• Not checked yetcites May, 2011

In the paper

“It has been suggested that abnormal functioning of the ANS might responsible for some of the symptoms associated with IBS”

What the sources say

• Not checked yetcites Bockus et al., 1928

In the paper

“Activation of the HPA axis is central to the stress response”

What the sources say

• Not checked yetcites Frodl and O’Keane, 2013

In the paper

“Whether these changes in ANS activity are unique to IBS or, as with the other changes described here, are common to all patients with CPP is as yet unclear.”

In the paper

“Furthermore, the sample size was small and the symptoms not validated by a medical practitioner.”

In the paper

“A number of reasons have been proposed to explain why increases in brain volume are seen with these specific pain conditions in contrast to the other conditions investigated, including the fact that the patients are generally younger, pain is intermittent/cyclical/provoked as opposed to continuous and that most women with these conditions do not use large doses of pain modifying drugs for a”

What the sources say

• Not checked yetcites Schweinhardt et al., 2008

In the paper

“For example, a reduction in circulating cortisol could increase the chances of repeated urinary tract infections, or central sensitization could predispose to the development of chronic whiplash after a minor car accident.”

In the paper

“In the context of dysmenorrhoea, Tu and colleagues observed regionally specific (prefrontal and orbitofrontal cortices) metabolic increases in the brain during dysmenorrhoea, which they suggest may be related to negative psychological symptoms”

What the sources say

• Not checked yetcites Tu et al., 2009

In the paper

“It is of particular concern that many of the symptoms of CPP start in adolescence or early adult life (Zondervan et al., 1999a, b; Brosens et al., 2013), a time when the CNS is very plastic (Blakemore and Choudhury, 2006; Kalia, 2008) and thus potentially more vulnerable to repeated episodes of pain.”

What the sources say

• Not checked yetcites Blakemore and Choudhury, 2006; Kalia, 2008

In the paper

“Unfortunately, we currently know very little about why some people develop chronic pain.”

In the paper

“There are a number of reasons as to why this might occur including common predisposing factors, such as genetics (Diatchenko et al., 2007) or psychological/cognitive state (for review, see Blackburn-Munro (2004)), and similar neural mechanisms (Giamberardino et al., 2010).”

What the sources say

• Not checked yetcites Diatchenko et al., 2007
• Not checked yetcites Blackburn-Munro (2004)
• Not checked yetcites Giamberardino et al., 2010

In the paper

“Chronic fatigue syndrome (CFS) has been correlated with vulvodynia (Arnold et al., 2007) and IBS (Whitehead et al., 2002), whilst endometriosis is associated with a variety of autoimmune and endocrine conditions including hypothyroidism, systemic lupus erythematosus and multiple sclerosis (Sinaii et al., 2002).”

What the sources say

• Not checked yetcites Arnold et al., 2007
• Not checked yetcites Whitehead et al., 2002

In the paper

“However, it is also plausible that the central changes secondary to one chronic pain condition could then predispose to the development of another (Woolf, 2011).”

What the sources say

• Not checked yetcites Woolf, 2011

In the paper

“It is plausible that these central changes contribute to the well-established disparity between the extent of disease observed at laparoscopy and the pain experienced (Vercellini et al., 2007) and to the persistence of pain despite adequate surgical treatment.”

What the sources say

• Not checked yetcites Vercellini et al., 2007

In the paper

“whilst depression enhances the affective component of pain, increasing unpleasantness, and appears to disrupt activity within a network of brain regions including the amygdala and inferior frontal gyrus”

What the sources say

• Not checked yetcites Berna et al., 2010

In the paper

“For example, a reduction in circulating cortisol could increase the chances of repeated urinary tract infections, or central sensitization could predispose to the development of chronic whiplash after a minor car accident.”

In the paper

“Furthermore, women with fertility concerns are more likely to undergo surgical treatment of their disease (Dunselman et al., 2014), thereby increasing the potential for further damage to pelvic and endometriotic nerves.”

What the sources say

• Not checked yetcites Dunselman et al., 2014

In the paper

“Such prompt treatment, as well as being welcomed by the patient, may prevent development or progression of central changes and potentially development of other symptoms/pain conditions, in addition to improving symptoms from any other pain conditions already present (Giamberardino et al., 2010).”

What the sources say

• Not checked yetcites Giamberardino et al., 2010

In the paper

“Although it remains to be ascertained whether central changes are a cause, effect or both of the painful symptoms, it appears likely that their presence has the potential to not only exacerbate symptoms, but also to predispose these women to the development of additional chronic conditions.”

In the paper

“Other chronic conditions have also been associated with HPA axis dysfunction, including CFS and major depression, as has post-traumatic stress disorder (Yehuda et al., 1991; Pariante and Lightman, 2008; Papadopoulos and Cleare, 2012).”

What the sources say

• Not checked yetcites Yehuda et al., 1991; Pariante and Lightman, 2008; Papadopoulos and Cleare, 2012

In the paper

“Furthermore, if this symptom significantly impacts on their relationship, both self-esteem and social support may be reduced, potentially further worsening their pain experience (Culley et al., 2013).”

What the sources say

• Not checked yetcites Culley et al., 2013

In the paper

“This is common practice in other chronic pain conditions (Dworkin et al., 2010; Richards et al., 2012) but is currently poorly investigated in CPP specifically (Sator-Katzenschlager et al., 2005; Horne et al., 2012).”

What the sources say

• Not checked yetcites Dworkin et al., 2010; Richards et al., 2012
• Not checked yetcites Sator-Katzenschlager et al., 2005; Horne et al., 2012

In the paper

“These include direct compression/infiltration of nerves by the lesions, inflammatory pain due to the enhanced inflammatory environment of the pelvis and ‘neuropathic’ pain secondary to damage of pelvic nerves during surgery or of the new nerves directly infiltrating the lesions (Stratton and Berkley, 2011).”

What the sources say

• Not checked yetcites Stratton and Berkley, 2011

In the paper

“A similar situation has been previously proposed to occur in rheumatoid arthritis (Straub and Cutolo, 2001).”

What the sources say

• Not checked yetcites Straub and Cutolo, 2001

In the paper

“Moreover, it could underlie the frequently discussed, though not well proven (Raphael et al., 2004), link between abuse and chronic pain.”

What the sources say

• Not checked yetcites Raphael et al., 2004

In the paper

“A major criticism of many of the studies cited in this review is that they are ‘snapshot’ studies and therefore they can only inform us about central factors that occur in association with chronic pain, rather than giving us any information about cause and effect.”