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Manual Therapy 12 (2007) 86–97 Diagnosis and classification of pelvic girdle pain disorders—Part 1: A mechanism based approach within a biopsychosocial framework Peter B. O'Sullivan, Darren J. Beales School of Physiotherapy, Curtin University of Technology, GPO Box U1987, Perth, WA 6845, Australia Received 20 February 2007; received in revised form 21 February 2007; accepted 21 February 2007 The diagnosis and classification of pelvic girdle pain (PGP) disorders remains controversial despite a proliferation of research into this field. The majority of PGP disorders have no identified pathoanatomical basis leaving a management vacuum. Diagnostic andtreatment paradigms for PGP disorders exist although many of these approaches have limited validity and are uni-dimensional (i.e.
biomechanical) in nature. Furthermore single approaches for the management of PGP fail to benefit all. This highlights thepossibility that ‘non-specific' PGP disorders are represented by a number of sub-groups with different underlying pain mechanismsrather than a single entity.
This paper examines the current knowledge and challenges some of the common beliefs regarding the sacroiliac joints and pelvic function. A hypothetical ‘mechanism based' classification system for PGP, based within a biopsychosocial framework is proposed.
This has developed from a synthesis of the current evidence combined with the clinical observations of the authors. It recognises thepresence of both specific and non-specific musculoskeletal PGP disorders. It acknowledges the complex and multifactorial nature ofchronic PGP disorders and the potential of both the peripheral and central nervous system to promote and modulate pain. It isproposed that there is a large group of predominantly peripherally mediated PGP disorders which are associated with either‘reduced' or ‘excessive' force closure of the pelvis, resulting in abnormal stresses on pain sensitive pelvic structures. It acknowledgesthat the interaction of psychosocial factors (such as passive coping strategies, faulty beliefs, anxiety and depression) in these paindisorders has the potential to promote pain and disability. It also acknowledges the complex interaction that hormonal factors mayplay in these pain disorders. This classification model is flexible and helps guide appropriate management of these disorders within abiopsychosocial framework. While the validity of this approach is emerging, further research is required.
r 2007 Elsevier Ltd. All rights reserved.
Keywords: Pelvic girdle pain; Sacroiliac joint; Classification; Pain mechanisms; Motor control 1. Pelvic girdle pain disorders (Maksymowych et al., 2005). However, PGP disordersmore commonly present as ‘non-specific' (no identified Pelvic girdle pain (PGP) disorders represent a small but pathoanatomical basis), often arising during or shortly significant group of musculoskeletal pain disorders. Pain after pregnancy (Berg et al., 1988; Ostgaard et al., 1991; associated with the sacroiliac joints (SIJs) and/or the Bastiaanssen et al., 2005) or following traumatic injury to surrounding musc Author's personal copy
uloskeletal and ligamentous structures the pelvis (O'Sullivan et al., 2002a; Chou et al., 2004).
represent a sub-group of these disorders. Specific Frequently these pain disorders are misdiagnosed and inflammatory pain disorders of the SIJs, such as managed as lumbar spine disorders, as pain originating sacroiliitis, are the most readily identified PGP disorders from the lumbar spine commonly refers to the SIJ region.
However, there is growing evidence that PGP disorders manifest as a separate sub-group with a unique clinical Corresponding author. Tel.: 61 8 9266 3629; fax: 61 8 9266 3699.
E-mail address: (P.B. O'Sullivan).
presentation and the need for specific management.
1356-689X/$ - see front matter r 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.math.2007.02.001 P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 A number of PGP disorders do not resolve (Ostgaard while another group of subjects with SIJ pain (with a et al., 1996; Larsen et al., 1999; Albert et al., 2001; positive active straight leg raise test (ASLR)) demon- Noren et al., 2002; To and Wong, 2003), becoming strate impaired control of the pelvic floor (O'Sullivan chronic despite the absence of pathoanatomical ab- et al., 2002a; O'Sullivan and Beales, 2007). These normalities on radiological examination or signs of a findings highlight that; (i) there may be various under- systemic or inflammatory disorder from blood screening lying mechanisms that drive different PGP disorders, (Hansen et al., 2005). This leads to a broad diagnosis of and (ii) the need for a classification based approach a ‘non-specific' PGP disorder and leaves a diagnostic which guides targeted interventions for sub-groups of and management vacuum. These PGP disorders are subjects with PGP, which is based upon the underlying commonly associated with signs and symptoms indicat- pain mechanism(s) that drives the disorder.
ing that the pain originates from the SIJs and/or theirsurrounding connective tissue and myo-fascial struc-tures (Berg et al., 1988; Kristiansson and Svardsudd, 2. Challenging the beliefs regarding the sacroiliac joints 1996; Mens et al., 1999; Albert et al., 2000; Damen et al., 2001; Vleeming et al., 2002; O'Sullivan et al., 2002a;Laslett et al., 2003). However, identification of a painful The SIJ perhaps more than any other joint complex in structure does not provide insight into the underlying the body has been shrouded by an enormous amount of mechanism(s) that drives the pain (O'Sullivan, 2005a).
mystique within the field of Manual Therapy—with A number of theoretical models have been proposed complex, poorly validated and often confusing theories with regard to potential underlying pain mechanisms in and treatment approaches associated with it. Beliefs of PGP. Chiropractic, Osteopathic and Manual Therapy the clinician (that the pelvis is ‘displaced' or ‘unstable') models commonly propose that the SIJs can become commonly become the beliefs of the patients. For many ‘fixated' or ‘displaced' leading to positional faults. There patients these clinical labels can be detrimental with the are a series of complex clinical procedures proposed to potential to render the patient passively dependent on identify these so-called ‘positional faults' and treatment someone to ‘fix them', elevating anxiety levels, reinfor- with manipulation, mobilisation and/or muscle energy cing avoidance behaviours and promoting disability.
techniques has been suggested to rectify them (Don- Increased passive dependence and fear/anxiety has the Tigny, 1990; Sandler, 1996; Kuchera, 1997; Oldreive, potential to further increase the central drive of pain, 1998; Cibulka, 2002). Although manual and manipula- contributing to disability and the chronic pain cycle. It is tive techniques can result in short term pain modulation therefore important to be clear on the ‘facts' regarding (Wright, 1995), there is little evidence for the long term the SIJs and put them into the context of current benefits of SIJ manipulation or other passive treatments knowledge. The basic anatomy, biomechanics and used in isolation for the management of chronic PGP stability models proposed for the SIJ are documented disorders (Stuge et al., 2003). The selection of these elsewhere and as such will not be reviewed in full here techniques is often directed by treating the signs and (Pool-Goudzwaard et al., 1998; Lee and Vleeming, 2000; symptoms of the disorder rather than a valid and clear Vleeming et al., 2006).
diagnostic and classification paradigm based on themechanisms that underlie the pain disorder.
2.1. The facts regarding the SIJs More recently emphasis has been placed on enhancing motor control deficits in PGP disorders. This is based on  The SIJs are inherently stable (Vleeming et al., the premise that deficits in lumbo-pelvic motor control 1990a, b; Snijders et al., 1993a).
result in impaired load transference through the pelvis  The joints are designed for load transfer (Kapandji, and thereby contribute to a peripheral nociceptive drive 1982; Gray and Williams, 1989) and can safely of symptoms (Mens et al., 1996; Vleeming et al., 1996, transfer enormous compressive loading forces under 1990b; O'Sullivan et al., 2002a; O'Sullivan and Beales, normal conditions (Snijders et al., 1993a).
2007). There is growing evidence based on outcome  The SIJ has little movement in non-weight bearing studies that some PGP disorders do indeed respond well (average 2.5 degrees rotation) (Sturesson et al., 1989; Author's personal copy
targeted motor training interventions Brunner et al., 1991; Jacob and Kissling, 1995; (Stuge et al., 2004a, b; O'Sullivan and Beales, 2007).
Vleeming et al., 1992a, b), and even less in weight However, not all PGP disorders respond to these bearing (average 0.2 degrees rotation) (Sturesson et interventions (Stuge et al., 2006). Relevant to this inconsistency in outcome, is the existence of different  Movement of the SIJ cannot be reliably assessed by patterns of motor control impairments in PGP subjects.
manual palpation, particularly in weight bearing For instance increased pelvic floor activation has been (Sturesson et al., 2000; van der Wurff et al., 2000a, b).
documented in subjects with peripartum PGP consistent  Due to its anatomical makeup, intra-articular dis- with SIJ involvement (Pool-Goudzwaard et al., 2005), placements within the SIJs are unlikely to occur. No P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 study utilising a valid measurement instrument has 3. Classification of pelvic girdle pain disorders identified positional faults of the SIJ—in fact theconverse is true (Tullberg et al., 1998).
Chronic pain disorders are complex, multifactorial  Distortions of the pelvis observed clinically are likely and need to be considered within a biopsychosocial to occur secondary to changes in pelvic and trunk framework. A different cluster of potential physical, muscle activity, resulting in directional strain and pathoanatomical, psychosocial, hormonal and neuro- not positional changes within the SIJs themselves physiological factors is associated with each disorder (Tullberg et al., 1998).
(Fig. 1). Needless to say the interactions between these  No study utilising a valid measurement tool has factors are very complex. This highlights the need for a demonstrated that pelvic manipulation alters the flexible classification and management approach for position of the pelvic joints (Tullberg et al., 1998)— each disorder.
pain relief from these procedures is likely to result Although the SIJs and the surrounding ligamentous from nociceptive inhibition based on neuro-inhibi- and myofascial structures are potentially nociceptive tory factors and/or altered patterns of motor activity structures (Fortin et al., 1994a, b; Vilensky et al., 2002), (Wright, 1995; Pickar, 2002).
from a neurophysiologic perspective it is well known  Asymmetrical laxity of the SIJs, as measured with that ongoing pain can be mediated both peripherally Doppler imaging, has been shown to correlate with and centrally, and the forebrain can greatly modulate moderate to severe levels of symptoms in subjects this process (Zusman, 2002; Woolf, 2004). It is therefore with peripartum PGP (Damen et al., 2001). General- logical that PGP disorders can potentially be both ised SIJ laxity is not associated with peripartum peripherally or centrally induced/maintained, with a pelvic pain (Damen et al., 2001).
different balance or dominance of peripheral and central  When clinical signs of reduced force closure have factors associated with each disorder (Elvey and been identified (positive ASLR), the increased move- O'Sullivan, 2005).
ment is identified at the symphysis pubis—not the Furthermore with PGP there is the potential con- SIJs (Mens et al., 1999). It is likely that the torsional tributing role of sex hormones. There are a number of forces occurring at the SIJs can cause strain across possible pathways by which hormones may influence pain sensitised tissue.
PGP (Fig. 2). There is some evidence that sex hormones  Pain from the SIJ is located primarily over the joint are active in pain modulation (Aloisi and Bonifazi, (inferior sulcus) and may refer distally, but not to the 2006). Sex hormones are also known to influence the low back (Fortin et al., 1994a, b; Schwarzer et al., inflammatory process in inflammatory pain disorders 1995; Dreyfuss et al., 1996; Maigne et al., 1996; (Schmidt et al., 2006). Furthermore sex hormones may Slipman et al., 2000; Young et al., 2003; van der alter collagen synthesis (Kristiansson et al., 1999), Wurff et al., 2006).
thereby effecting the load capacity of the pelvis. There  SIJ pain disorders can be diagnosed using clinical is some evidence to support the role of hormones in PGP examination (Laslett et al., 2003; Young et al., 2003; disorders, with higher serum levels of progesterone and Petersen et al., 2004; Laslett et al., 2005a, b). This relaxin in early pregnancy being found in subjects who includes the finding of pain primarily located to the develop peripartum PGP compared to those who do not inferior sulcus of the SIJs, positive pain provocation (Kristiansson et al., 1999). Via these processes sex tests for the SIJs and an absence of painful lumbar hormones have the potential to contribute to PGP in spine impairment.
different clinical presentations (Fig. 2). Further research  The SIJ has many muscles that act to compress is required to clarify how the role of hormones may and control it (force closure), thereby enhancing differ in these various presentations of PGP.
pelvic stability (creating stiffness) allowing for The proposed classification model for PGP disorders effective load transfer via the pelvis during a variety is based on the potential mechanisms that can drive the of functional tasks (Vleeming et al., 1990a, b, 1995; PGP. This classification approach is not exhaustive but Snijders et al., 1993a, b; ; Snijders et al., 1998; Damen rather provides a framework to guide the clinician.
et al., 2002; Richardson et al., 2002; O'Sullivan Based on the mechanism(s) that underlie these disorders et al., 2002a; Author's personal copy
Pool-Goudzwaard et al., 2004; van and operating within a biopsychosocial framework, the Wingerden et al., 2004; Mens et al., 2006; Snijders classification model aims to facilitate the diagnosis, et al., 2006).
classification (Fig. 3), and targeted management of these  PGP disorders may be associated with ‘excessive' 3.1. The clinical examination (O'Sullivan et al., 2002a; Hungerford et al., 2003;Pool-Goudzwaard et al., 2005; O'Sullivan and The clinical examination is critical to the clinical Beales, 2007).
reasoning process that underpins this diagnosis and P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 motor activation) peripheral pain g − acute, sub-acute, chronic − intermittent vs constant − local / generalised / referred Patho-anatomical factors
- identification of - mechanism of injury if present - disorder history (pregnancy related) - disorder stage - pain behaviour − provocative and relieving factors - mechanical vs non-mechanical provocation - +ve active straight leg raise - SIJ provocation tests - adaptive vs mal-adaptive movement behaviours - motor control impairments ( - disability levels - activity levels / conditioning / strength / muscle endurance - work / home environment / lifestyle - ergonomic factors - peripheral sensitisation - hormonal factors - central sensitisation - sympathetic nervous system activity - somatic complaints - glial cell activation Genetic factors
potentially influencing all other domains- Author's personal copy
− family, friends, work − passive vs active Social factors
- caring for children - medical advice and treatment - support structures - compensation (emotional, financial) - cultural factors - socio-economic factors Psychological factors
- personality type - beliefs & attitudes towards pain disorder - coping strategies - hyper-vigilance - fear avoidance behaviour - emotions- fear / anxiety / depression / anger / helplessness - illness behaviour P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 Collagen
Modulation of
of Neural
Organisation of
Central Nervous
Fig. 2. Possible actions of hormones in the development and maintenance of pelvic girdle pain. Factors affecting hormone levels are also presented.
Non-specific pelvic pain disorders
Specific pelvic pain disorders
- Specific inflammatory pain
Centrally mediated pelvic girdle
Peripherally mediated pelvic girdle
disorders (sacroiliitis)
- Infections
(+/- cognitive / psychosocial factors - Fractures
resulting in central pain amplification) Dominant
Excessive force
- Medical management
- Management advice

- Motor learning
- Motor learning
- Medical management
within cognitive
within cognitive
- Functional rehabilitation
Psychological (cognitive framework
behavioural therapy), medical, (reduce force closure Author's personal copy
functional rehabilitation - Functional
- Functional
Fig. 3. Mechanism based classification and management of chronic pelvic girdle pain disorders.
classification framework. In the interview process all the  pain pattern (intermittent versus constant, 24 hour following need to be considered: pain pattern, sleep disturbances),  pain intensity,  the pain area (localised versus generalised pain can  pain behaviour (specific movements and postures that indicate peripheral from central pain drive), provoke and relieve pain), P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97  levels of disability and impairment, areas or to assess for coexisting pathology/dysfunction  specific pain history (specific and surrounding events in these regions.
that may have contributed to the development of viour, beliefs and levels of impairment with his/her  family history of PGP, clinical presentation (observing for avoidance beha-  the patient's pain coping strategies (active versus viours, catastrophising, etc.) is important to determine whether cognitive issues such as fear of movement are  the patient's pain beliefs, present and dominant. On synthesis of this material  presence of avoidant behaviours due to fear of a diagnosis and classification of the PGP disorder can movement and other psychosocial factors including present and past history of anxiety and depression,  pacing patterns and concurrent presence of disorders of continence and/ 4. Specific pelvic girdle pain disorders or sexual dysfunction.
Pelvic girdle pain disorders associated with specific Review of radiology if present and screening for pathological processes include inflammatory arthritis, specific causes of PGP may be indicated from this sacroiliitis, infections and fractures. These disorders are process. This allows for a determination as to the area amenable to specific diagnosis with appropriate blood and nature of the pain.
screening and radiological investigation. They can be A thorough physical examination is then required to associated with altered patterns of motor control determine the pain source and behaviour in relationship behaviour that are ‘adaptive' and/or protective of the to the patient's movement behaviour. Physical tests underlying disorder. Treating the signs and symptoms of these disorders by manual therapy and/or specificexercise interventions is generally not appropriate as itdoes not address the underlying pain mechanism of the  Palpation of the inferior sulcus of the SIJ and disorder. Physiotherapy may be limited to management surrounding pelvic ligamentous and myo-fascial of the sequelae of the underlying disease/pathological processes especially in disorders such as ankylosing  Provocative tests for the SIJ and surrounding ligamentous and myofascial structures (Laslett etal., 2003, 2005a, b; Young et al., 2003; Petersen et al.,2004).
5. Non-specific pelvic girdle pain disorders  The ASLR test in supine and prone as a test of load transfer, with a positive test resulting in normal- 5.1. Non-specific inflammatory pelvic girdle pain isation of ASLR with the addition of pelvic compression (Mens et al., 1999; O'Sullivan andBeales, 2007).
There appears to be a group of PGP disorders that  Careful analysis of the pain provoking and relieving present as being inflammatory in nature, rather than activities and postures (functional impairments) high- mechanical. They are characterised by constant, dis- lighted from the interview to identify the presence of abling and non-remitting pain, located in the SIJs, that impairments of movement and motor control as well is provoked with weight bearing, pelvic compression as avoidance behaviours and to determine their (such as a SIJ belt) and with SIJ pain provocation tests.
relationship to the pain disorder. Determining These disorders may show areas of increased uptake on whether altered motor patterns are adaptive/protec- bone scan but are not linked to a specific inflammatory tive (pain is aggravated when motor control patterns disorder diagnosis based on blood screening. They may are normalised) or mal-adaptive (pain is relieved be relieved with rest, anti-inflammatory medications and when motor control deficits are normalised) is local steroid injections to the SIJ, but are resistant to  Tests for specific Author's personal copy
muscle function for the pelvic floor, Although the exact underlying mechanism for these the abdominal wall, the back muscles, iliopsoas, PGP disorders is unknown it is possible that hormonal quadratus lumborum, the gluteal muscles and pir- factors play a role, particularly given their common onset in the first trimester of pregnancy or painmodulation with hormonal cycles or changes. Although In addition the adjacent areas of the lumbar spine the role of sex hormones is purely speculative in this (including neural tissue) and hip joints should be group of patients, further research into their effect is thoroughly investigated to rule out involvement of these P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 5.2. Peripherally mediated (mechanically induced) pelvic ciated with spinal movement related pain and/or spinal girdle pain disorders movement impairment. A specific pain source at the SIJand its surrounding structures can usually be identified These disorders are characterised by localised pain by specific provocative manual tests (Laslett et al., 2003, that has a defined anatomical location (SIJ and 2005a, b; Young et al., 2003; Petersen et al., 2004). These associated connective tissue and myofascial struc- disorders are usually associated with consistent local tures+/ symphysis pubis). The pain is intermittent in motor control changes (inhibition or excitation). These nature and is provoked and relieved by specific postures disorders usually have a clear mechanism or time of and activities related to vertical or directional loading in onset (either repeated strain or direct trauma to the weight bearing positions. They are not usually asso- pelvis or peripartum PGP). It is proposed that these Mal-adaptive chronic pelvic girdle pain disorders where motor control impairments
represent dominant underlying driving mechanism for pain
Tissue injury / localised pain Excessive force closure
- hyper-activity of pelvic muscles
Factors that may influence pain and motor with excessive joint compression pathoanatomical ligamentous laxity Non resolution
mal-adaptive patterns adopted - education − regarding pain mechanism poor coping strategies - identify factors that drive motor system neurophysiological prolonged neuromuscular response - cognitive behavioural approach excessive reduced force closure - relaxation of motor system - relaxation strategies coping strategies abnormal tissue loading - graded movement restoration - functional restoration - normalise movement behaviour compensation genetic Reduced force closure
Resolution of the disorder
- motor control deficit of pelvic
stabilising muscles with loss of force
Author's personal copy
- education − regarding pain mechanism - cognitive behavioural motor control intervention - pain control (avoid provocation)- specific motor activation - retrain faulty postures and movements - normalise movement behaviour - functional restoration Fig. 4. Sub-classification of pelvic girdle pain disorders with a primary peripheral nociceptive drive. Peripheral drive is perpetuated by mal-adaptivemotor control dysfunctions.
P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 disorders may be classified into two clinical subgroups these in isolation tend not to benefit the long term outcome of the disorder. There is evidence that longlever exercise regimes may aggravate these disorders 5.2.1. Reduced force closure (Mens et al., 2000). These disorders can be further sub- The first group represents disorders where the grouped based on their pattern of motor control peripheral pain drive is associated with excessive strain dysfunction. Different combinations of motor control to the sensitised SIJs and/or surrounding connective deficits may be found within the local lumbopelvic tissue and myofascial structures secondary to ligamen- muscles such as is observed in low back pain disorders tous laxity (Damen et al., 2001), coupled with motor that result in different directional (vertical, rotational) control deficits of muscles that control force closure of strain patterns within the pelvis (O'Sullivan, 2005b).
the SIJs (O'Sullivan et al., 2002a; Hungerford et al., Management of these disorders focuses on function- 2003; O'Sullivan and Beales, 2007). These motor control ally enhancing force closure across the pelvic structures deficits may have originally developed secondary to the based on the specific motor control deficits present. The pain disorder, but now their presence is mal-adaptive as aim of the intervention is to provide functional the resultant ‘reduced forced closure' leads to impaired activation of the motor system in order to control pain load transfer through the pelvis, acting as a mechanism and restore functional capacity (Fig. 4). There is good for ongoing strain and peripheral nociceptive drive for evidence to support the efficacy of this type of approach the pain disorder. Hormonal influences on collagen in these disorders (Stuge et al., 2004a, b; O'Sullivan and synthesis may be an important factor in this group.
Beales, 2007).
These disorders are commonly associated with post- partum PGP and present with a positive ASLR test 5.2.2. Excessive force closure (normalised with pelvic compression) (O'Sullivan et al., The second group is defined by a group of PGP 2002a; Stuge et al., 2004a). The motor control deficits disorders where the peripheral nociceptive drive is based that present in these disorders are variable and are on excessive, abnormal and sustained loading of linked to a loss of functional patterns of co-contraction sensitised pelvic structures (SIJs and surrounding con- of the local force closure muscles of the pelvis (such as nective tissue and/or myofascial structures) from the the pelvic floor, the transverse abdominal wall, the excessive activation of the motor system local to the pelvis lumbar multifidus, iliopsoas and the gluteal muscles).
(excessive force closure). This patient group presents This is commonly associated with attempts to stabilise with localised pain to the SIJs and commonly also the the lumbopelvic region via co-activation of other trunk surrounding connective tissue and myo-fascial struc- muscles (quadratus lumborum, thoracic erector spinae, tures (such as the pelvic floor and piriformis muscles) as diaphragm, external oblique, rectus abdominis and well as positive pain provocation tests. However this vertical fibres of internal oblique). Their primary group of patients has a negative ASLR (no feeling of functional impairments are associated with pain in heaviness). Compression (manual or using a SIJ belt), is weight bearing postures such as sitting, standing and often provocative, as is local muscle activation (pelvic walking, or loaded activities inducing rotational pelvic floor, transverse abdominal wall, back muscles, iliop- strain associated with coupled spine/hip loading activ- soas, gluteal muscles). They commonly hold habitual ities (i.e. cycling and rowing resulting in posterior erect lordotic lumbopelvic postures associated with high rotational strain on ilium). These patients commonly levels of co-contraction across various muscles such as assume postures that are associated with inhibition of the abdominal wall, pelvic floor, local spinal muscles the local pelvic muscles (pelvic floor, transverse abdom- (lumbar multifidus, psoas major) and in some cases the inal wall, lumbar multifidus and the gluteal muscles) gluteal and piriformis muscles which may become pain such as ‘sway' standing, ‘hanging off one leg', ‘slump' sensitised. These motor control responses often become sitting or ‘thoracic upright' sitting (O'Sullivan et al., habitual secondary to excessive cognitive muscle train- 2002b, 2006; Dankaerts et al., 2006; Sapsford et al., ing and/or muscle guarding of the lumbopelvic muscles, 2006) and present with a loss of lumbopelvic control and are themselves mal-adaptive (provocative). These (inability to disassociate pelvic from thoracic move- patients report pain relief from cardiovascular exercise, Author's personal copy
disorders may be relieved with a SIJ belt relaxation, assuming passive spinal postures (which they (Ostgaard et al., 1994; Mens et al., 2006), training seldom do), as well as short-term relief with stretching, optimal alignment of their spino-pelvic posture and soft tissue massage, manipulation, muscle energy functional enhancement of local co-contraction strate- techniques and cessation of stabilisation exercises. These gies across the pelvis with relaxation of the thoraco- disorders are commonly associated with the patient's pelvic musculature (O'Sullivan and Beales, 2007). These belief that their pelvis is ‘unstable' or ‘displaced' and disorders may gain short term relief from mobilisation, that more muscle contraction or ‘pelvic re-alignment' is muscle energy techniques, soft tissue massage and beneficial. This is commonly reinforced by the treating manipulation of the SIJs (clinical observation) although therapist's beliefs. These disorders may be induced by P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 intensive ‘stabilisation exercises', Pilates, ball exercise, 5.3. Central nervous system driven pelvic girdle pain and cognitive muscle exercise training of the abdominal wall, lumbar multifidus and pelvic floor. Patients withthese disorders are commonly anxious, under high levels The mechanisms of central nervous system sensitisa- of stress, highly active and seldom rest.
tion and/or glial cell activation and their involvement in Management of these disorders focuses on reducing the maintenance of chronic pain states are well known force closure across the pelvic structures (Fig. 4). This is (Woolf, 2004; Hansson, 2006), and may persist even carried out with a combination of approaches such as: once a peripheral nociceptive drive is removed or general as well as targeted relaxation strategies, breath- has resolved. In this way chronic PGP can be poten- ing control, muscle inhibitory techniques, enhancing tially mediated largely or entirely via the central passive/relaxed spinal postures, pacing strategies, hy- nervous system. In these disorders, the pain may have drotherapy, cessation of stabilisation exercise training, initially presented as a peripherally driven disorder, but and a focus on cardiovascular exercise. Anecdotally this once chronic, the pain does not have a presentation approach appears very effective although clinical studies consistent with a peripheral pain source. These pain are required to validate this.
disorders are commonly associated with widespread,severe, and constant pain that is non-mechanical in 5.2.3. Psychosocial influences on peripherally mediated nature. They lack a specific detectable peripheral pelvic girdle pain nociceptive drive or pathological basis and are com- It is known that chronic pain and PGP disorders are monly associated with widespread allodynia. These commonly associated with not only physical but also disorders are associated with high levels of physical psychosocial and cognitive impairments (Main and impairment and social impact, and may be associated Watson, 1999; Bastiaenen et al., 2004, 2006; Linton, with widespread and inconsistent motor control dis- 2000, 2005) (Fig. 1). Even in the presence of a dominant turbances and abnormal pain behaviours that are peripheral nociceptive drive to PGP (such as described secondary to the pain state and do not clearly drive above), cognitive and psychosocial factors are invariably the pain disorder. These disorders are often associated linked to these disorders influencing pain amplification with dominant psychosocial factors (somatisation, and disability levels to varying degrees. This highlights catastrophising, pathological fear and/or elevated anxi- the need for a biopsychosocial (behavioural) approach ety, depression, as well as significant social factors such to understanding and managing chronic PGP disorders as past history of sexual abuse etc).
even when they are peripherally mediated in nature.
Although these disorders appear to represent a small Psychosocial factors have the potential to both ‘up' sub-group of chronic PGP disorders, they are highly regulate or ‘down' regulate pain. For example, a disabling and resistant to physical interventions. Man- classification of ‘reduced force closure' may be asso- agement of these disorders must be multidisciplinary ciated with cognitive impairments such as faulty beliefs, involving medical and psychological management as a elevated anxiety levels and passive coping strategies that primary approach. Functional rehabilitation should aim amplifies pain via the central nervous system and to enhance normal general body function and address promotes high levels of disability associated with the abnormal pain behaviours without a focus on pain.
pain disorder. In this case the intervention must address Passive treatments and rehabilitation that focuses on the cognitive impairments associated with the disorder specific muscle control strategies may simply act to within the motor learning intervention such as by reinforce abnormal pain behaviours and hyper-vigilance promoting accurate beliefs, relaxation techniques and in these patients.
active coping strategies. On the other hand, if the same‘reduced force closure' classification is associated with 5.4. Genetics and pelvic girdle pain positive beliefs, active coping strategies and limitedfunctional impairments, then the primary focus can be The role that genetics play with non-specific PGP placed more on the physical impairments of the disorder disorders is largely unknown although its potential to establish pain control.
must be recognised. Subjects with PGP are more Author's personal copy
classification of ‘excessive force closure' likely to have a mother or sister who also has PGP may be associated with underlying stress and anxiety. In (Mogren and Pohjanen, 2005; Larsen et al., 1999) this case dealing with these cognitive factors with which may implicate a genetic link although social relaxation, breathing strategies, pacing and cardiovas- influences may also mediate this effect. A genetic cular exercise is a critical adjunct to the motor learning predisposition in PGP patients related to changes in management of these disorders. Where the psychosocial/ action of relaxin is proposed as one mechanism of cognitive components of the disorders are resistant to genetic influence on PGP (MacLennan and MacLennan, change, complementary psychological and/or medical 1997). Clearly further research into genetic influences intervention may be essential.
is required.
P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 asymmetric laxity of the sacroiliac joints. Acta Obstetricia etGynecologica Scandinavica 2001;80(11):1019–24.
This paper provides a broad clinical classification Damen L, Spoor CW, Snijders CJ, Stam HJ. Does a pelvic belt influence sacroiliac joint laxity? Clinical Biomechanics 2002;17(7): model for the management of chronic PGP disorders. It is a flexible, mechanism-based approach within a multi- Dankaerts W, O'Sullivan P, Burnett A, Straker L. Altered patterns of factorial biopsychosocial framework. The classification superficial trunk muscle activation during sitting in nonspecific model directs appropriate management based on the chronic low back pain patients: importance of subclassification.
underlying mechanism/s that drives the pain. Although there is growing support for the validity of this DonTigny RL. Anterior dysfunction of the sacroiliac joint as a major factor in the etiology of idiopathic low back pain syndrome.
approach, further research is required into this area.
Physical Therapy 1990;70(4):250–65 discussion 262–265.
Dreyfuss P, Michaelsen M, Pauza K, McLarty J, Bogduk N. The value of medical history and physical examination in diagnosing sacroiliac joint pain. Spine 1996;21(22):2594–602.
Elvey R, O'Sullivan PB. A contemporary approach to manual therapy.
In: Jull GA, Boyling JD, editors. Grieve's modern manual therapy.
Many thanks to Dr Britt Stuge and Dr Wim 3rd ed. Edinburgh: Churchill Livingstone; 2005. p. 471–93 Dankaerts for their clinical insights and advice in the (Chapter 33).
final stages of writing this manuscript.
Fortin JD, Aprill CN, Ponthieux B, Pier J. Sacroiliac joint: pain referral maps upon applying a new injection/arthrography techni-que. Part II: Clinical evaluation. Spine 1994a;19(13):1483–9.
Fortin JD, Dwyer AP, West S, Pier J. Sacroiliac joint: pain referral maps upon applying a new injection/arthrography technique. Part Part 2 of this Masterclass can be viewed online only at I: Asymptomatic volunteers. Spine 1994b;19(13):1475–82.
Gray H, Williams PL. Gray's anatomy. Edinburgh, Melbourne, New York: Churchill Livingstone; 1989.
Hansen A, Jensen DV, Larsen EC, Wilken-Jensen C, Kaae BE, Frolich S, et al. Postpartum pelvic pain—the ‘‘pelvic joint syndrome'': afollow-up study with special reference to diagnostic methods. ActaObstetricia et Gynecologica Scandinavica 2005;84(2):170–6.
Albert H, Godskesen M, Westergaard J. Evaluation of clinical tests Hansson E. Could chronic pain and spread of pain sensation be used in classification procedures in pregnancy-related pelvic joint induced and maintained by glial activation? Acta Physiologica pain. European Spine Journal 2000;9(2):161–6.
Albert H, Godskesen M, Westergaard J. Prognosis in four syndromes Hungerford B, Gilleard W, Hodges P. Evidence of altered lumbopelvic of pregnancy-related pelvic pain. Acta Obstetricia et Gynecologica muscle recruitment in the presence of sacroiliac joint pain. Spine Aloisi AM, Bonifazi M. Sex hormones, central nervous system and Jacob HA, Kissling RO. The mobility of the sacroiliac joints in healthy pain. Hormones and Behavior 2006;50(1):1–7.
volunteers between 20 and 50 years of age. Clinical Biomechanics Bastiaanssen JM, de Bie RA, Bastiaenen CH, Essed GG, van den Brandt PA. A historical perspective on pregnancy-related low back Kapandji IA. The physiology of the joints: annotated diagrams of the and/or pelvic girdle pain. European Journal of Obstetrics & mechanics of the human joints. Edinburgh, Melbourne, New York: Gynecology and Reproductive Biology 2005;120(1):3–14.
Bastiaenen CH, de Bie RA, Wolters PM, Vlaeyen JW, Bastiaanssen Churchill Livingstone; 1982.
JM, Klabbers AB, et al. Treatment of pregnancy-related pelvic Kristiansson P, Svardsudd K. Discriminatory power of tests applied in girdle and/or low back pain after delivery design of a randomized back pain during pregnancy. Spine 1996;21(20):2337–43.
clinical trial within a comprehensive prognostic cohort study. BMC Kristiansson P, Svardsudd K, von Schoultz B. Reproductive hormones Public Health 2004;467.
and aminoterminal propeptide of type III procollagen in serum as Bastiaenen CH, de Bie RA, Wolters PM, Vlaeyen JW, Leffers P, early markers of pelvic pain during late pregnancy. American Stelma F, et al. Effectiveness of a tailor-made intervention for Journal of Obstetrics and Gynecology 1999;180(1 Part 1): pregnancy-related pelvic girdle and/or low back pain after delivery: Short-term results of a randomized clinical trial. BMC Musculos- Kuchera ML. Treatment of gravitational strain pathophysiology. In: keletal Disorders 2006;7(1):19.
Vleeming A, Mooney V, Dorman T, Snijers C, Stoeckart R, Berg G, Hammar M, Moller-Nielsen J, Linden U, Thorblad J. Low editors. Movement, Stability and Low Back Pain: The Essen- tial Role of the Pelvis. Edinburgh: Churchill Livingstone; 1997.
p. 477–99.
Brunner C, Kissling R, Author's personal copy
Jacob HA. The effects of morphology and Larsen EC, Wilken-Jensen C, Hansen A, Jensen DV, Johansen S, histopathologic findings on the mobility of the sacroiliac joint.
Minck H, et al. Symptom-giving pelvic girdle relaxation in pregnancy. I: Prevalence and risk factors. Acta Obstetricia et Chou LH, Slipman CW, Bhagia SM, Tsaur L, Bhat AL, Isaac Z, et al.
Inciting events initiating injection-proven sacroiliac joint syn- Laslett M, Young SB, Aprill CN, McDonald B. Diagnosing painful drome. Pain Medicine 2004;5(1):26–32.
sacroiliac joints: A validity study of a McKenzie evaluation and Cibulka MT. Understanding sacroiliac joint movement as a guide to sacroiliac provocation tests. Australian Journal of Physiotherapy the management of a patient with unilateral low back pain. Manual Laslett M, Aprill CN, McDonald B, Young SB. Diagnosis of sacroiliac Damen L, Buyruk HM, Guler-Uysal F, Lotgering FK, Snijders CJ, joint pain: validity of individual provocation tests and composites Stam HJ. Pelvic pain during pregnancy is associated with of tests. Manual Therapy 2005a;10(3):207–18.
P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 Laslett M, McDonald B, Tropp H, Aprill CN, Oberg B. Agreement Oldreive WL. A classification of, and a critical review of the literature between diagnoses reached by clinical examination and available on, syndromes of the sacroiliac joint. The Journal of Manual and reference standards: a prospective study of 216 patients with Manipulative Therapy 1998;6(1):24–30.
lumbopelvic pain. BMC Musculoskeletal Disorders 2005b;628.
Ostgaard HC, Andersson GB, Karlsson K. Prevalence of back pain in Lee D, Vleeming A. Current concepts on pelvic impairment. In: pregnancy. Spine 1991;16(5):549–52.
Proceedings of the 7th Scientific Conference of the International Ostgaard HC, Zetherstrom G, Roos-Hansson E, Svanberg B.
Federation of Orthopaedic Manipulative Therapists, Perth, WA, Reduction of back and posterior pelvic pain in pregnancy. Spine Australia, 2000. p. 465–91.
Linton SJ. A review of psychological risk factors in back and neck Ostgaard HC, Roos-Hansson E, Zetherstrom G. Regression of pain. Spine 2000;25(9):1148–56.
back and posterior pelvic pain after pregnancy. Spine 1996;21(23): Linton SJ. Do psychological factors increase the risk for back pain in the general population in both a cross-sectional and prospective Petersen T, Olsen S, Laslett M, Thorsen H, Manniche C, Ekdahl C, et analysis? European Journal of Pain 2005;9(4):355–61.
al. Inter-tester reliability of a new diagnostic classification system MacLennan AH, MacLennan SC. Symptom-giving pelvic girdle for patients with non-specific low back pain. Australian Journal of relaxation of pregnancy, postnatal pelvic joint syndrome and developmental dysplasia of the hip. Acta Obstetricia et Gyneco- Pickar JG. Neurophysiological effects of spinal manipulation. The logica Scandinavica 1997;76(8):760–4.
Spine Journal 2002;2(5):357–71.
Maigne JY, Aivaliklis A, Pfefer F. Results of sacroiliac joint double Pool-Goudzwaard AL, Vleeming A, Stoeckart R, Snijders CJ, Mens block and value of sacroiliac pain provocation tests in 54 patients JMA. Insufficient lumbopelvic stability: a clinical, anatomical and with low back pain. Spine 1996;21(16):1889–92.
biomechanical approach to ‘‘a-specific'' low back pain. Manual Main CJ, Watson PJ. Psychological aspects of pain. Manual Therapy Pool-Goudzwaard A, Hoek Van Dijke G, Van Gurp M, Mulder P, Maksymowych WP, Inman RD, Salonen D, Dhillon SS, Williams M, Snijders C, Stoeckart R. Contribution of pelvic floor muscles Stone M, et al. Spondyloarthritis research Consortium of Canada to stiffness of the pelvic ring. Clinical Biomechanics 2004;19(6): magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis. Arthritis & Rheumatism Pool-Goudzwaard AL, Slieker Ten Hove MC, Vierhout ME, Mulder PH, Pool JJ, Snijders CJ, et al. Relations between pregnancy- Mens JM, Vleeming A, Stoeckart R, Stam HJ, Snijders CJ. Under- related low back pain, pelvic floor activity and pelvic floor standing peripartum pelvic pain. Implications of a patient survey.
dysfunction. International Urogynecology Journal and Pelvic Spine 1996;21(11):1363–9 discussion 1369–1370.
Floor Dysfunction 2005;16(6):468–74.
Mens JM, Vleeming A, Snijders CJ, Stam HJ, Ginai AZ. The active Richardson CA, Snijders CJ, Hides JA, Damen L, Pas MS, Storm J.
straight leg raising test and mobility of the pelvic joints. European The relation between the transversus abdominis muscles, sacroiliac Spine Journal 1999;8(6):468–74.
joint mechanics, and low back pain. Spine 2002;27(4):399–405.
Mens JM, Snijders CJ, Stam HJ. Diagonal trunk muscle exercises in Sandler SE. The management of low back pain in pregnancy. Manual peripartum pelvic pain: a randomized clinical trial. Physical Sapsford RR, Richardson CA, Stanton WR. Sitting posture affects Mens JM, Damen L, Snijders CJ, Stam HJ. The mechanical effect of a pelvic floor muscle activity in parous women: an obser- pelvic belt in patients with pregnancy-related pelvic pain. Clinical vational study. Australian Journal of Physiotherapy 2006;52(3): Mogren IM, Pohjanen AI. Low back pain and pelvic pain during Schmidt M, Naumann H, Weidler C, Schellenberg M, Anders S, pregnancy: prevalence and risk factors. Spine 2005;30(8):983–91.
Straub RH. Inflammation and sex hormone metabolism. Annals of Noren L, Ostgaard S, Johansson G, Ostgaard HC. Lumbar back and the New York Academy of Sciences 2006;106:9236–46.
posterior pelvic pain during pregnancy: a 3-year follow-up.
Schwarzer AC, Aprill CN, Bogduk N. The sacroiliac joint in chronic European Spine Journal 2002;11(3):267–71.
low back pain. Spine 1995;20(1):31–7.
O'Sullivan P. Diagnosis and classification of chronic low back pain Slipman CW, Jackson HB, Lipetz JS, Chan KT, Lenrow D, Vresilovic disorders: Maladaptive movement and motor control impairments EJ. Sacroiliac joint pain referral zones. Archives of Physical as underlying mechanism. Manual Therapy 2005a;10(4):242–55.
Medicine and Rehabilitation 2000;81(3):334–8.
O'Sullivan PB. ‘Clinical Instability' of the lumbar spine: its patholo- Snijders C, Vleeming A, Stoeckart R. Transfer of lumbosacral load to gical basis, diagnosis and conservative management. In: Jull GA, iliac bones and legs. Part 1: Biomechanics of self-bracing of the Boyling JD, editors. Grieve's modern manual therapy. 3rd ed.
sacroiliac joints and its significance for treatment and exercise.
Edinburgh: Churchill Livingstone; 2005b. p. 311–31 (Chapter 22).
Clinical Biomechanics 1993a;8(6):285–94.
O'Sullivan PB, Beales DJ. Changes in pelvic floor and diaphragm Snijders C, Vleeming A, Stoeckart R. Transfer of lumbosacral load to kinematics and respiratory patterns in subjects with sacroiliac joint iliac bones and legs. Part 2: Loading of the sacroiliac joints when pain following a motor learning intervention: A case series. Manual lifting in a stooped posture. Clinical Biomechanics 1993b;8(6): Therapy 2007; in press.
O'Sullivan PB, Beales Author's personal copy
DJ, Beetham JA, Cripps J, Graf F, Lin IB, et al.
Snijders CJ, Ribbers MT, de Bakker HV, Stoeckart R, Stam HJ. EMG Altered motor control strategies in subjects with sacroiliac joint recordings of abdominal and back muscles in various standing pain during the active straight-leg-raise test. Spine 2002a;27(1):E1– postures: validation of a biomechanical model on sacroiliac joint stability. Journal of Electromyography and Kinesiology 1998;8(4): O'Sullivan PB, Grahamslaw KM, Kendell M, Lapenskie SC, Moller NE, Richards KV. The effect of different standing and sitting Snijders CJ, Hermans PF, Kleinrensink GJ. Functional aspects of postures on trunk muscle activity in a pain-free population. Spine cross-legged sitting with special attention to piriformis muscles and sacroiliac joints. Clinical Biomechanics 2006;21(2):116–21.
O'Sullivan P, Dankaerts W, Burnett A, Chen D, Booth R, Carlsen C, Stuge B, Hilde G, Vollestad N. Physical therapy for pregnancy-related et al. Evaluation of the flexion relaxation phenomenon of the trunk low back and pelvic pain: a systematic review. Acta Obstetricia et muscles in sitting. Spine 2006;31(17):2009–16.
P.B. O'Sullivan, D.J. Beales / Manual Therapy 12 (2007) 86–97 Stuge B, Laerum E, Kirkesola G, Vollestad N. The efficacy of a Vleeming A, Stoeckart R, Volkers AC, Snijders CJ. Relation between treatment program focusing on specific stabilizing exercises for form and function in the sacroiliac joint. Part I: Clinical anatomical pelvic girdle pain after pregnancy: a randomized controlled trial.
aspects. Spine 1990a;15(2):130–2.
Vleeming A, Volkers AC, Snijders CJ, Stoeckart R. Relation between Stuge B, Veierod MB, Laerum E, Vollestad N. The efficacy of a form and function in the sacroiliac joint. Part II: Biomechanical treatment program focusing on specific stabilizing exercises for aspects. Spine 1990b;15(2):133–6.
pelvic girdle pain after pregnancy: a two-year follow-up of a Vleeming A, Buyruk HM, Stoeckart R, Karamursel S, Snijders CJ. An randomized clinical trial. Spine 2004b;29(10):E197–203.
integrated therapy for peripartum pelvic instability: a study of the Stuge B, Morkved S, Haug Dahl H, Vollestad N. Abdominal biomechanical effects of pelvic belts. American Journal of and pelvic floor muscle function in women with and without Obstetrics and Gynecology 1992a;166(4):1243–7.
long lasting pelvic girdle pain. Manual Therapy 2006;11(4): Vleeming A, Van Wingerden JP, Dijkstra PF, Stoeckart R, Snijders CJ, Stijnen T. Mobility in the sacroiliac joints in the elderly: a Sturesson B, Selvik G, Uden A. Movements of the sacroiliac joints.
A roentgen stereophotogrammetric analysis. Spine 1989;14(2): Vleeming A, Pool-Goudzwaard AL, Stoeckart R, van Wingerden JP, Sturesson B, Uden A, Vleeming A. A radiostereometric analysis of Snijders CJ. The posterior layer of the thoracolumbar fascia. Its movements of the sacroiliac joints during the standing hip flexion function in load transfer from spine to legs. Spine 1995;20(7): test. Spine 2000;25(3):364–8.
To WW, Wong MW. Factors associated with back pain symptoms in Vleeming A, Pool-Goudzwaard AL, Hammudoghlu D, Stoeckart R, pregnancy and the persistence of pain 2 years after pregnancy. Acta Snijders CJ, Mens JM. The function of the long dorsal sacroiliac Obstetricia et Gynecologica Scandinavica 2003;82(12):1086–91.
ligament: its implication for understanding low back pain. Spine Tullberg T, Blomberg S, Branth B, Johnsson R. Manipulation does not alter the position of the sacroiliac joint. A roentgen Vleeming A, de Vries HJ, Mens JM, van Wingerden JP. Possible role stereophotogrammetric analysis. Spine 1998;23(10):1124–8 discus- of the long dorsal sacroiliac ligament in women with peripartum pelvic pain. Acta Obstetricia et Gynecologica Scandinavica van der Wurff P, Hagmeijer RH, Meyne W. Clinical tests of the sacroiliac joint. A systemic methodological review. Part 1: Vleeming A, Albert H, Ostgaard HC, Stuge B, Sturesson B. European reliability. Manual Therapy 2000a;5(1):30–6.
Guidelines on the Diagnosis and Treatment of Pelvic Girdle Pain van der Wurff P, Meyne W, Hagmeijer RH. Clinical tests of the (Concept Version), 2006. /
sacroiliac joint. A systematic methodological review. Part 2: Woolf CJ. Pain: moving from symptom control toward mechanism- validity. Manual Therapy 2000b;5(2):89–96.
specific pharmacologic management. Annals of Internal Medicine van der Wurff P, Buijs EJ, Groen GJ. Intensity mapping of pain referral areas in sacroiliac joint pain patients. Journal of Wright A. Hypoalgesia post-manipulative therapy: a review of a Manipulative and Physiological Therapeutics 2006;29(3):190–5.
van Wingerden JP, Vleeming A, Buyruk HM, Raissadat K. Stabiliza- tion of the sacroiliac joint in vivo: verification of muscular Young S, Aprill C, Laslett M. Correlation of clinical examination contribution to force closure of the pelvis. European Spine Journal characteristics with three sources of chronic low back pain. The Spine Journal 2003;3(6):460–5.
Vilensky JA, O'Connor BL, Fortin JD, Merkel GJ, Jimenez AM, Zusman M. Forebrain-mediated sensitization of central pain path- Scofield BA, et al. Histologic analysis of neural elements in the ways: ‘non-specific' pain and a new image for MT. Manual human sacroiliac joint. Spine 2002;27(11):1202–7.
Author's personal copy


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Ob schwein, ob huhn, ob gnitze

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