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A new view on hypocortisolism

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Om lavt kortisol-nivå og at det har en beskyttende effekt på kroppen etter langvarig høyt kortisol-nivå. En ny måte å se det på. Det er faktisk en overlevelsesmekanisme. Hvis vi ikke greier å skru av stresset eller fjerne oss fra den stressende livssituasjonen, vil kroppen etter hvert skru av stressresponsen og vi blir oversensitive for enhver utfordring. Utmattelse, muskelsmerter og fibromyalgi blir resultatet. Men likevel er det bedre for organismen enn videre stressresons. Studien forteller hvordan kortisol påvirker sentralnervesystemet, immunsystemet, oppvåkningsresponsen om morgenen, sickness responce, allostatic load, m.m.

http://cfids-cab.org/cfs-inform/Hypotheses/fries.etal05.pdf

Low cortisol levels have been observed in patients with different stress-related disorders such as chronic fatigue syndrome, fibromyalgia, and post- traumatic stress disorder. Data suggest that these disorders are characterized by a symptom triad of enhanced stress sensitivity, pain, and fatigue.

We propose that the phenomenon of hypocortisolism may occur after a prolonged period of hyperactivity of the hypothalamic–pituitary– adrenal axis due to chronic stress as illustrated in an animal model. Further evidence suggests that despite symptoms such as pain, fatigue and high stress sensitivity, hypocortisolism may also have beneficial effects on the organism. This assumption will be underlined by some studies suggesting protective effects of hypocortisolism for the individual.

Since the work of Selye (1936), stress has been associated with an activation of the hypothalamic– pituitary–adrenal (HPA) axis resulting in an increased release of cortisol from the adrenal glands. In recent years, a phenomenon has been described that is characterized by a hyporespon- siveness on different levels of the HPA axis in a number of stress-related states. This phenomenon, termed ‘hypocortisolism’, has been reported in about 20–25% of patients with stress-related dis- orders such as chronic fatigue syndrome (CFS), chronic pelvic pain (CPP), fibromyalgia (FMS), post-traumatic stress disorder (PTSD), irritable bowel syndrome (IBS), low back pain (LBP), burn- out, and atypical depression (Griep et al., 1998; Heim et al., 1998, 2000; Pruessner et al., 1999; Gold and Chrousos, 2002; Gur et al., 2004; Roberts et al., 2004; Rohleder et al., 2004). When hypo- cortisolemic, all these disorders may share affiliated syndromes characterized by a triad of enhanced stress sensitivity, pain, and fatigue.

However, despite different definitions we know today that there is a considerable overlap between the disorders.

In the early 1990s, Hudson and colleagues were amongst the first addressing this issue. They published a study on the comorbidity of FMS with medical and psychiatric disorders in which they reported a higher prevalence of migraine, IBS, and CFS, as well as higher lifetime rates of depression and panic disorder in patients with FMS (Hudson et al., 1992).

Thus, numerous studies on male war veterans have reported an association between PTSD and symp- toms such as fatigue, joint pain, and muscle pain (Engel et al., 2000; Ford et al., 2001).

These alterations of HPA axis are determined by (1) a reduced biosynthesis or release of the respective releasing factor/hormone on different levels of the HPA axis (CRF/AVP from the hypothalamus, ACTH from the pituitary, or cortisol from the adrenal glands) accompanied by a subsequent decreased stimulation of the respective target receptors, (2) a hypersecretion of one secretagogue with a subsequent down-regulation of the respective target receptors, (3) an enhanced sensitivity to the negative feedback of glucocorti- coids, (4) a decreased availability of free cortisol, and/ or (5) reduced effects of cortisol on the target tissue, describing a relative cortisol resistance (Heim et al., 2000; Raison and Miller, 2003).

Several years ago we postulated that hypocortiso- lism/a hyporeactive HPA axis might develop after prolonged periods of stress together with a hyper- activity of the HPA axis and excessive glucocorti- coid release (Hellhammer and Wade, 1993). This proposed time course with changes in HPA axis activity from hyper- to hypocortisolism resembles the history of patients with stress-related disorders who frequently report about the onset of ‘hypo- cortisolemic symptoms’ (fatigue, pain, stress sen- sitivity) after prolonged periods of stress, e.g. work stress, infection, or social stress (Buskila et al., 1998; Van Houdenhove and Egle, 2004)

Thinking about the potential cause/reason for changes in HPA axis activity from hyper- to hypocortisolism one might consider the body’s self-adjusting abilities as an important factor. Self-adjusting abilities play a significant role in survival of the organism by counteracting the enduring increased levels of glucocorticoids, and protecting the organism against the possible dele- terious effects thereof.

Poten- tial mechanisms of the ‘HPA axis adjustment’ are (1) the down-regulation of specific receptors on different levels of the axis (hypothalamus, pitu- itary, adrenals, target cells), (2) reduced biosyn- thesis or depletion at several levels of the HPA axis (CRF, ACTH, cortisol) and/or (3) increased negative feedback sensitivity to glucocorticoids (Hellhammer and Wade, 1993; Heim et al., 2000).

The suppressed stress response after administration of dexamethasone demonstrates an increased sensi- tivity to glucocorticoid negative feedback on the level of the pituitary.

The duration, intensity, number and chronicity of stressors may further pronounce these effects. The low-dose dexamethasone test may be the most sensitive measure of this condition.

The HPA axis plays an important role in the regulation of the SNS. CRF seems to increase the spontaneous discharge rate of locus coeruleus (LC) neurons and enhances norepinephrine (NE) release in the prefrontal cortex (Valentino, 1988; Valentino et al., 1993; Smagin et al., 1995), whereas glucocorticoids seem to exert more inhibitory effects on NE release.

Glucocorticoids are the most potent anti-inflam- matory hormones in the body. They act on the immune system by both suppressing and stimulating pro- and anti-inflammatory mediators. While they promote Th2 development, for example by enhan- cing interleukin (IL)-4 and (IL)-10 secretion by macrophages and Th2 cells (Ramierz et al., 1996), they inhibit inflammatory responses and suppress the production and release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF- alpha), IL-1 and IL-6 (see Franchimont et al., 2003).

An important role of glucocorticoids during stress is to suppress the production and activity of pro- inflammatory cytokines, thus restraining the inflammatory reaction and preventing tissue destruction (see McEwen et al., 1997; Ruzek et al., 1999; Franchimont et al., 2003).

Therefore, a hypocortisolemic stress response, as observed in patients with stress-related disorders, may result in an overactivity of the immune system in terms of increased inflammatory responses due to impaired suppressive effects of low cortisol levels (see Heim et al., 2000; Rohleder et al., 2004). This assumption is supported by studies reporting elevated levels of pro-inflammatory cytokines in patients with stress-related disorders such as PTSD, CFS, and FMS (Maes et al., 1999; Patarca-Montero et al., 2001; Thompson and Barkhuizen, 2003; Rohleder et al., 2004).

Assessing the cortisol awakening response in pregnant women, preliminary results from our laboratory suggest that women with higher daily stress load showed lower cortisol levels in the morning compared to women with normal to low daily stress load. This result suggests a possible prevention of harmful stimulatory effects of maternal cortisol on placental CRF, which plays a major role in the initiation of delivery (Rieger, 2005).

The term ‘sickness response’ refers to non-specific symptoms such as fatigue, increased pain sensi- tivity, depressed activity, concentration difficul- ties, and anorexia that accompany the response to infection (Hart, 1988; Maier and Watkins, 1998). Sickness behavior at the behavioral level appears to be the expression of a central motivational state that reorganizes the organism’s priority to cope with infectious pathogens (Hart, 1988).

Further evidence for the protective effects of the development of a hypocortisolism refers to the allostatic load index. The term ‘allostatic load’ was irstly introduced by McEwen and Stellar (1993) describing the wear and tear of the body and brain resulting from chronic overactivity or inactivity of physiological systems that are normally involved in adaptation to environmental challenge. Allostatic load results when the allostatic systems (e.g. the HPA axis) are either overworked or fail to shut off after the stressful event is over or when these systems fail to respond adequately to the initial challenge, leading other systems to overreact (McEwen, 1998). In this context, results of Hell- hammer et al. (2004) demonstrate a significantly higher allostatic load index in older compared to younger subjects with the exception of hypocorti- solemic elderly who had a comparable allostatic load to young people even though they scored far higher on perceived stress scales. Considering the fact that allostatic load has been associated with a higher risk for mortality, these data suggest that a hypocortisolemic response to stress may rather be protective than damaging.

Low cortisol levels in the case of pregnant women may protect the mother and the child against the risk of pre-term birth, which could be harmful for both of them. Similarly, low cortisol levels in those individuals who are repeatedly or continuously exposed to intense immune stimuli may be beneficial for health and survival.

Similarly, low cortisol levels in those individuals who are repeatedly or continuously exposed to intense immune stimuli may be beneficial for health and survival. Most strikingly, the demonstration of a low allostatic load index in hypocortisolemic subjects suggests that a down-regulation of the HPA axis in chroni- cally stressed subjects protects those subjects against the harmful effects of a high allostatic load index.

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Scratch collapse test for evaluation of carpal and cubital tunnel syndrome.

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Viser hvilken klinisk relevanse scratch collapse test har for å finne hvor nerver er i klem.

http://www.ncbi.nlm.nih.gov/pubmed/18984333

For the new test, the patient resisted bilateral shoulder external rotation with elbows flexed. The area of suspected nerve compression was lightly «scratched,» and then resisted shoulder external rotation was immediately repeated. Momentary loss of shoulder external rotation resistance on the affected side was considered a positive test.

For carpal tunnel syndrome, sensitivities were 64%, 32%, and 44% for the scratch collapse test, Tinel’s test, and wrist flexion/compression test, respectively. For cubital tunnel syndrome, sensitivities were 69%, 54%, and 46% for the scratch collapse test, Tinel test, and elbow flexion/compression test, respectively. The scratch collapse test had the highest negative predictive value (73%) for carpal tunnel syndrome. Tinel’s test had the highest negative predictive value (98%) for cubital tunnel syndrome.

The scratch collapse test had significantly higher sensitivity than Tinel’s test and the flexion/nerve compression test for carpal tunnel and cubital tunnel syndromes. Accuracy for this test was 82% for carpal tunnel syndrome and 89% for cubital tunnel syndrome.

Mer utfyllende studie om Scratch Collapse her: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880669/

Though the exact mechanism of the scratch collapse test is unknown, we believe it may represent a gross physical manifestation of the “cutaneous silent period.” This EMG-demonstrated phenomenon is observed following noxious stimuli. A brief pause of voluntary muscle contraction is demonstrated following stimulation of a cutaneous nerve [24]. The scratch collapse yields a similar reflex response. We propose that as the nervi-nervorum at the site of neuritis are stimulated, an ipsilateral central inhibition is transiently activated. It is not surprising that this response would be most robust at the focus of the neuritis.

The scratch collapse examination shares several features with the cutaneous silent period. Both phenomena occur after a noxious stimulus, are very resistant to habituation, are able to override voluntary muscle contraction, and result in a deferment in resistance in a pattern that corresponds to the withdrawal of the extremity into a position of protection (e.g., in this case, internally rotating the arms in against the body) [9, 11, 13, 16, 17]. From an evolutionary standpoint, such a reflex would be important in survival.

The test offers an advantage over these other tests in that it appears to precisely localize the site of nerve compression.

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Undervisning om nervekompresjon nevropati og kirurgi i armen

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Nervekompresjon begynner i en mild variant, hvor myelinlaget rundt nervene fortsatt er tykt og fint. Blodsirkulasjonen hemmes. Smerter og paraestesier kommer og går. Tinels tegn er negativt tidlig i progresjonen. Scratch-Collapse Test viser hvor i nervebanen det er kompresjonproblemer(f.eks. doublecrush syndrome).

Blir moderat, hvor myelinlaget blir tynt. Det blir hevelse i nerven og bindevevet blir tykkere i området. Smerter er konstante og musklene svekkes. Det tar 3-4 mnd å bygge opp myelinlaget igjen når kompresjonen er rettet opp.

Og alvorlig, hvor myelinlaget er borte. Nervetrådene forvinner mer og mer. Atrofi og nummenhet i musklene. Når kompresjonen er borte repareres nerven ca.3 cm i måneden.

http://prezi.com/mjuaxe0cwwbr/?utm_campaign=share&utm_medium=copy&rc=ex0share

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Om alt som er galt med fysio

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Her er et fantastisk innlegg fra en fysioterapeut. Dette er så spot-on at han ble kalt inn på teppet av ledelsen på sitt undiversitet og forsøkt kneblet. De mente han burde ha ventet med å skrive slikt til han hadde minst 5 år mer erfaring. Noe som bare viser hvordan autoriteter mangler evne til fleksibilitet, og at såkalte evidensbaserte behandlingsformer ikke greier å tilpasse seg ny forskning. Fysioterapi henger 50 år etter. Jeg har samlet alle referansene for lettere tilgang.

http://blog.theravid.com/patient-care/redefining-evidence-ebp-in-experience-cut/

How does one justify the use of ultrasound when the biophysical (Baker et al 2001) and clinical (Robertson et al 2001) effects have been so thoroughly disproven?

Why are we still taught that we are molders of connective tissue, when the forces required to create plastic deformation of connective tissue ranges between 50 and 250 pounds of force (Threlkeld 1992)?

When are we going to accept the fact that our palpatory exams lack reliability (French et al 2000) (Lucas et al 2009)

and validity (Najm et al 2003) (Landel et al 2008) (Preece et al 2008)?

When will we stop telling students, colleagues, and patients that pain is related to their posture, muscle length, muscle strength, or biomechanics (Edmondston et al 2007) (Lewis et al 2005) (Nourbakhsh et al 2002)?

When will we cease blaming pain on something found on an image (Reilly et al 2006) (Beattie et al 2005) (Borenstein et al 2001)?

When will we stop thinking that we can change someone’s static posture with strengthening (Walker et al 1987) (Diveta et al 1990)?

When we teach these things to students and say them to our patients, it is misleading at best and fear inducing and hurtful at worst (Zusman 2012).

“In My Experience”remain the three most dangerous words in medicine.

This is perhaps even doubly so in the world of physical therapy, given the litany of non-specific effects that go into a treatment encounter (Hall et al 2010) (Miciak et al 2012).

Physical therapists are in a unique position to make a significant impact on the burden of chronic pain, however, we fail to live up to our potential by holding onto a postural-structural-biomechanical model that has been proven ineffective and incorrect (Lederman 2011).

We need to familiarize ourselves with the work of people like Ronald Melzack, Patrick Wall, Louis Gifford, David Butler and Lorimer Moseley.

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Skin Biopsy as a Diagnostic Tool in Peripheral Neuropathy: Correlates of Intraepidermal Nerve Fiber Density

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Denne nevner mye om nevropati og sammenhengen mellom small fiber density og smerte, pluss at den nevner hvordan trening og steroidbehandling øker tettheten igjen. Viktigst prinsipp å hente fra denne artikkelen er at c-fiber tettheten sier noe om intensiteten på smerten, men ikke noe om smertetilstanden. Man kan ha lav tetthet og lite smerte, men om man får smerte er intensiteten desto høyere. Man må desverre logge inn for å få opp linkene.

http://www.medscape.org/viewarticle/563262_6

In diabetic neuropathy, patients with pain had lower IENF densities than did asymptomatic patients, but IENF density did not correlate with pain intensity within the group of symptomatic patients.[82]

In patients with impaired glucose tolerance, diet and exercise induced a slight recovery of IENF density that was associated with a reduction in pain symptoms.[83] Similarly, epidermal reinnervation coincided with pain reduction after steroid treatment.[71]

CORRELATES OF INTRAEPIDERMAL NERVE FIBER DENSITY

Clinical Picture, Etiology and Neuropathic Pain

The clinical picture of small-fiber neuropathy is dominated by spontaneous and stimulus-evoked positive sensory symptoms—namely thermal and pinprick hypoesthesia—that can mask the signs of small-fiber loss. Only a few studies have attempted to correlate IENF density with validated clinical scales. In patients with diabetic neuropathy, a negative correlation between IENF density and neuropathy symptom score was reported.[53,56]These studies also showed that the extent of epidermal denervation correlated with the duration of diabetes but not with hemoglobin A1C levels, suggesting that IENF density might be useful as a marker of neuropathy progression. A recent study found a high concordance between reduced IENF density and loss of pinprick sensation in the foot.[61]

Skin biopsy has allowed small-fiber neuropathy to be demonstrated in restless legs syndrome[75] and erythromelalgia.[76] In systemic diseases, such as systemic lupus erythematosus, sarcoidosis, Sjögren’s syndrome, celiac disease and hypothyroidism, skin biopsy has enabled correlations to be found between neuropathic symptoms and small-fiber degeneration.[52,65,77–79]Although IENF density is a general marker of axonal integrity in peripheral neuropathies, it cannot be used to directly address the question of etiology. Skin biopsy findings can, however, indirectly contribute to the assessment of etiology. For example, in 40% of patients with small-fiber neuropathy diagnosed only after skin biopsy, oral glucose tolerance testing revealed a previously undetected impaired glucose tolerance.[49] Similarly, the distribution of IENF loss can help to differentiate between a non-length-dependent sensory neuronopathy and a length-dependent axonal neuropathy,[78,80] thereby leading to focused screening for associated diseases.

The relationship between IENF density and neuropathic pain remains uncertain. In HIV neuropathy, IENF density correlated inversely with pain severity when assessed by the patient, but not when the Gracely Pain Scale was used.[66] Another study found only a trend towards an inverse correlation between IENF density and pain intensity in this setting.[81] In diabetic neuropathy, patients with pain had lower IENF densities than did asymptomatic patients, but IENF density did not correlate with pain intensity within the group of symptomatic patients.[82] In patients with impaired glucose tolerance, diet and exercise induced a slight recovery of IENF density that was associated with a reduction in pain symptoms.[83] Similarly, epidermal reinnervation coincided with pain reduction after steroid treatment.[71]In length-dependent neuropathies, therefore, more-severe IENF loss seems to increase the risk of developing pain, the intensity of which might decrease in parallel with recovery of IENF density.

In postherpetic neuralgia, on the basis of evidence of relatively preserved skin innervation in the area of severe allodynia, normal thermal sensory function, pain relief in response to topical lidocaine, and worsening of pain with application of capsaicin, surgical removal of painful skin has been attempted.[84] After initial relief, pain increased, became intractable, and spread to previously unaffected dermatomes, suggesting the involvement of central mechanisms in the pathogenesis of neuropathic pain.

Sensory Nerve Conduction Studies

Sural sensory nerve action potential (SNAP) amplitude, which reflects the integrity of largediameter fibers, showed concordance with IENF density in the distal part of the leg in patients with large-fiber or mixed small-fiber and largefiber neuropathy. Not surprisingly, skin biopsy analysis seemed to be more sensitive than sural nerve conduction studies for diagnosing smallfiber neuropathy.[62] One study,[85] however, showed that in patients with symptoms of small-fiber neuropathy and normal sural nerve conduction, reduced IENF density correlated with a decrease in SNAP amplitude in the medial plantar nerve. This finding suggests subclinical involvement of the most-distal large fibers in small-fiber neuropathy.

Psychophysical Tests

The detection of thermal and pain thresholds using quantitative sensory testing has been widely used to assess the function of small nerve fibers. Although this approach is useful in population studies, it is an unreliable tool for diagnosing small-fiber neuropathy in clinical practice.[86] Moreover, the size of the probe used for the test can affect the results.[87]

In view of the fact that unmyelinated fibers and thinly myelinated fibers convey warm and cold sensation, respectively, thermal thresholds would be expected to correlate with IENF density. In diabetic neuropathy, IENF density was found to be inversely correlated with thermal and pain thresholds, showing the highest correlation with warm threshold.[53,56,82]Similarly, in Guillain–Barré syndrome lower IENF density was associated with increased warm threshold.[67]One study reported a significant correlation between cold pain threshold and signs of large-fiber impairment.[59]By contrast, others studies did not find any correlation between quantitative sensory testing results and IENF density.[45,51,88]

Autonomic Tests

As IENFs are somatic unmyelinated fibers, their density would not be expected to correlate with autonomic fiber function. Intriguingly, however, in patients with Guillain–Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, lower IENF density was associated with a higher risk of developing dysautonomia.[64,67]These findings suggest that the integrity of IENFs might reflect the integrity of the whole class of small nerve fibers, including autonomic fibers. A few studies have investigated the correlation between IENF density and the results of a quantitative sudomotor axonal reflex test in patients with painful neuropathy and autonomic symptoms in order to test the hypothesis that IENF density and sweat output might decrease concomitantly. IENF density correlated with test results in one study,[63] but not in another.[51] In leprosy neuropathy, reduced nicotine-induced axon-reflex sweating correlated with decreased innervation of sweat glands.[88]

Nonconventional Neurophysiological Tests

Laser-evoked potentials (LEPs) have been used to investigate peripheral and central nociceptive pathways in trigeminal neuralgia and peripheral neuropathies. Late LEPs, reflecting Aδ-fiber activation, are delayed in patients with neuropathic pain, but can be enhanced when the pain has a psychogenic origin.[89] Recording of ultralate LEPs, reflecting activation of unmyelinated C-fibers, is less reliable than recording of late LEPs, thereby limiting the overall usefulness of LEPs in clinical practice. LEPs and skin biopsy findings have been examined in single case reports.[90]In two patients with Ross syndrome, abnormal LEPs correlated with decreased IENF density and increased thermal thresholds.[91] No study has yet looked for a correlation between results of skin biopsy analysis and recording of contact heat-evoked potentials, a technique that was recently proposed for investigating smallfiber function, but which cannot be used to assess C-fiber-related responses.[92]

Microneurography allows single-fiber recordings from nerves in awake patients. This technique demonstrated loss of nociceptive and skin sympathetic C-fiber activity that correlated with IENF and sweat gland denervation in a patient with hereditary sensory and autonomic neuropathy type IV.[20]In two patients with generalized anhidrosis, C-fiber recording and sweat gland innervation analysis distinguished postganglionic autonomic nerve fiber impairment from eccrine gland dysfunction.[34]

Sural Nerve Biopsy

The diagnosis of small-fiber neuropathy is better assessed by skin biopsy than by sural nerve biopsy.[57]IENF density can be reduced despite normal morphometry of unmyelinated and thinly myelinated fibers in sural nerve biopsy.[58] In a large comparative study,[62] skin and sural nerve biopsy findings were concordant in 73% of patients, but in 23% of patients IENF density was the only indicator of small-fiber neuropathy. Skin biopsy offers the opportunity to differentiate small nerve fibers with somatic function from those with autonomic function, thereby giving it a further advantage over nerve biopsy. In Charcot–Marie–Tooth disease and related hereditary neuropathies, a biopsy sample of the glabrous skin demonstrated the typical neuropathological abnormalities known from sural nerve studies.[5,6]

Immunohistochemical studies demonstrated IgM deposited specifically in the myelinated fibers of hairy and glabrous skin in patients with anti-myelin-associated-glycoprotein neuropathy.[93] Although skin biopsy can be contemplated in genetic and immune-mediated neuropathies, sural nerve biopsy should always be considered to confirm the diagnosis in inflammatory polyradiculoneuropathy with atypical presentation, or when vasculitic or amyloid neuropathy is suspected.

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High spontaneous activity of C-nociceptors in painful polyneuropathy.

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Viser hvordan c-fibre fyrer av i både smertefull og ikke-smertefull nevropati. Jo mer spontan aktivitet c-fibrene har, jo mer smerte oppleves.

http://www.ncbi.nlm.nih.gov/pubmed/22986070?dopt=Abstract

Polyneuropathy can be linked to chronic pain but also to reduced pain sensitivity. We investigated peripheral C-nociceptors in painful and painless polyneuropathy patients to identify pain-specific changes. Eleven polyneuropathy patients with persistent spontaneous pain and 8 polyneuropathy patients without spontaneous pain were investigated by routine clinical methods

The mean percentage of C-nociceptors being spontaneously active or mechanically sensitized was significantly higher in patients with pain (mean 40.5% and 14.6%, respectively, P=.02). The difference was mainly due to more spontaneously active mechanoinsensitive C-nociceptors (operationally defined by their mechanical insensitivity and their axonal characteristics) in the pain patients (19 of 56 vs 6 of 43; P=.02).

Hyperexcitability in mechanoinsensitive C-nociceptors was significantly higher in patients with polyneuropathy and pain compared to patients with polyneuropathy without pain, while the difference was much less prominent in mechanosensitive (polymodal) C-nociceptors. This hyperexcitability may be a major underlying mechanism for the pain experienced by patients with painful peripheral neuropathy.

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Double spikes to single electrical stimulation correlates to spontaneous activity of nociceptors in painful neuropathy patients.

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Viser hvor stor andel av c-fibrene som har spontan aktivitet ved nevropati, og hvor stor andel av de igjen som har dobbelt eller trippelt avfyring. Nevner at spontane avfyringer skjer i en viss andel av de uten multippel avfyring også. Og at selv uten smerte er det en liten andel av fibrene som fyrer av dobbelt. De konkluderer med at det er usikkert hvordan slik spontan aktivitetet egentlig er relatert til kliniske smertenivåer.

http://www.ncbi.nlm.nih.gov/pubmed/22154219

Multiple firing of C nociceptors upon a single electrical stimulus has been suggested to be a possible mechanism contributing to neuropathic pain. Because this phenomenon maybe based on a unidirectional conduction block, it might also be related to neuropathic changes without a direct link to pain.

In 11 of 105 nociceptors, double spiking was found, with 1 fibre even showing triple spikes on electrical stimulation.

There was a significant association between spontaneous activity and multiple spiking in C nociceptors, with spontaneous activity being present in 9 of 11 fibres with multiple spiking, but only in 21 of 94 nociceptors without multiple spiking (P<.005, Fisher exact test).

Among the 75 C nociceptors without spontaneous activity, only 2 nociceptors showed multiple spiking.

In 8 neuropathy patients without pain, double spiking was found only in 4 of 90 nociceptors

Multiple spiking of nociceptors coincides with spontaneous activity in nociceptors of painful neuropathy patients. We therefore conclude that rather than being a generic sign of neuropathy, multiple spiking is linked to axonal hyperexcitability and spontaneous activity of nociceptors. It is still unclear whether it also is mechanistically related to the clinical pain level.

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Double and triple spikes in C-nociceptors in neuropathic pain states: an additional peripheral mechanism of hyperalgesia.

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Om at nociceptive c-fibre i en nevropatisk tilstand kan fyre av dobbelt og trippelt ved en enkel stimulering. De forsterker signalene og bidrar til hyperalgesi (økt smerteopplevelse av en vanligvis normal smerteaktivering).

http://www.ncbi.nlm.nih.gov/pubmed/21130572

It was previously reported that in 5 patients with small-fiber neuropathy, neuropathic pain, and hyperalgesia, application of a single, brief electrical stimulus to the skin could give rise to 2 afferent impulses in a C-nociceptor fiber. These double spikes, which are attributed to unidirectional conduction failure at branch points in the terminal arborisation, provide a possible mechanism for hyperalgesia.

We here report that similar multiple spikes are regularly observed in 3 rat models of neuropathic pain: nerve crush, nerve suture, and chronic constriction injury. The proportion of nociceptor fibers exhibiting multiple spikes was similar (10.1-18.5%) in the 3 models, and significantly greater than the proportion in control (unoperated) animals (1.2%).

Whereas only double spikes had previously been described in patients, in these more extensive recordings from rats we found that triple spikes could also be observed after a single electrical stimulus. The results strengthen the suggestion that multiple spiking, because of impaired conduction in the terminal branches of nociceptors, may contribute to hyperalgesia in patients with neuropathic pain. Double and triple spikes in c-nociceptors, caused by impaired conduction in terminal branches, may be an important cause of hyperalgesia in patients with neuropathic pain.

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The Puzzle of Pelvic Pain: A Rehabilitation Framework for Balancing Tissue Dysfunction and Central Sensitization II: A Review of Treatment Considerations

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Om pelvic pain, en tilstand som mange opplever men som er vanskelig å behandle når man mangler elementer fra smertefroståelse. Dette gjelder egentlig alle kroniske smertetilstander. Alt forklares i denne viktige studien. Nevner biomedicinalism, ny forståelse av smerte, sentral sensitering, body maps, graded motor imagery, mirror therapy, m.m. Behandlingskonseptet som nevnes ligner det vi har etablert på Verkstedet.

http://www.thepelvicmessenger.org/upload/The_Puzzle_of_Pelvic_Pain___A_Rehabilitation.5.pdf
Physical therapists have been instrumental in guiding the medical system away from “end-organ” focus in the assessment and treatment of persistent pelvic pain. How- ever, for the most part physical therapists remain in a bio- medical model of treatment focusing on tissue dysfunction as a framework for the assessment and treatment of per- sistent pelvic pain. This article proposes a framework that integrates current understanding of local tissue dysfunc- tion with the wider context of sensitized protective mecha- nisms within the spinal cord and brain. Current concepts in pain science, particularly as it relates to the Neuromatrix and central sensitization, lead away from bio-medicalism towards a bio-psycho-social model of evaluation and treat- ment of persistent pelvic pain.

They proposed a framework for the treatment of pelvic floor dysfunction that moved away from the traditional strengthening approach of Kegel exercises. The idea that one cause of persistent pelvic pain and overactive bladder syndromes may be hypertonic muscles, instead of hypotonic muscles, has changed the treatment focus for some patient complaints of pelvic pain.

Physical therapists have made a compelling argument that many forms of persistent pelvic pain may have origins in myofascial dysfunction causing “end point” organ irritation, including swelling, redness, and pain in the bladder, prostate, testicles, or the vagina.4

Fitzgerald et al5 demonstrated in a multicenter feasibility study that physical therapy intervention of myofascial treatment applied to the perineum, abdominal wall, and pelvic floor demonstrated a 57% response rate compared with a 21% improvement rate with general massage therapy.

Butler7 describes biomedicalism as a “patho-anatomical search for a singular cause for chronic problems.” Waddel8 defines a biopsychosocial approach as an “individual-centered model that considers the person, their health problem and their social context.” The International Association for the Study of Pain describes pain as a “sensory and emotional experience”9 that encompasses both tissue nociception and the inter- pretation of the pain experience.

Globally, chronic pain and stress are at epidemic levels, as history shows, epidemics are best altered by education.7 The treatment of chronic pelvic pain has been well-recognized to have a mind (stress)- body (nociception) connection; however, education has not been widely used in this pain population to effectively link the 2 areas.

The summary of these conceptual changes is as follows:

  1. Pain is an output expression of the brain in response to a perception of threat.14,15 A therapeu- tic goal in persistent pain is to restore movement without triggering a protective pain response.
  2. Pelvic pain is complex. Psychosocial considerations include sexuality, cultural expectations, privacy, and religious issues.
  3. Chronic pain does not necessarily correlate with injury or disease, and nociception is neither neces- sary nor sufficient for a pain response.15,16
  4. The nervous system slides and glides as we move.16-18
  5. Neurophysiology-based pain education is an effec- tive adjunct to physical therapy intervention.12,13,19 Educating patients in the concepts of pain science, including neural plasticity, increases understanding and decreases the threat response.

Central sensitization encompasses “impaired functioning of brain-orchestrated descend- ing anti-nociceptive (inhibitory) mechanisms and (over) activation of descending and ascending pain facilitatory pathways.”21 The pain response operates within the entire system of nociceptive input, periph- eral neurogenic sensitization, and central sensitiza- tion.

Neurophysiology-based pain education forms the basis of treatment in central sensitization and refers to patient education about the role of central and peripheral processes in persistent pain.21 A patient who believes that local tissue dysfunction is the primary cause of a chronic pain state is likely to have thoughts and beliefs that limit normal mobility and function in the affected area.30

There are a mas- sive number of potential threats within the context of persistent pain.30 Using educational tools in the clinic to accurately explain pain helps give contextual meaning to the patient’s symptoms. Reduction of threat decreases the need for the engagement of active coping systems such as the sympathetic, immune, endocrine, and motor systems and the need for pro- tective pain states.16,38 Threats can be identified in a biopsychosocial framework (Table 1).

Table 1. Identifying Threats in a Biopsychosocial Frameworka

Biological
Worried x-rays showing “arthritis” Worried x-rays showing disc bulges Lack of specific diagnosis
Multiple medications ineffective Doing too much without pacing

Psychological
Fear of pain
Fear of not recovering
Fear of serious injury
Fear of reinjury Sadness/depression Hopelessness about recovery Attitude toward sexuality

Social
Withdrawn from family/joy Withdrawn from hobbies/sports Legal battle stress
Family stress/anger
Financial stress/worries
Work stress/anger

When sensitized neural states have been identified, the use of neurophysiology of pain education then flows into gentle guided exercises to normalize input into the sensory-motor cortex. Within the neuroma- trix, there are sensory maps, motor maps, and maps for smell, vision, and peripersonal space to name a few.39 The smudging of these body maps refers to a loss of normally distinctive localization and has been demonstrated in phantom limb pain,40,41 complex regional pain syndrome (CRPS),42 and chronic pain.43 Smudging in the sensory-motor cortex often occurs in the painful area and can also occur in the body part adjacent to the affected area on the homunculus.41,43

Patients with pelvic pain may report symptoms that could be indicative of smudging including the sensa- tion that their pelvic anatomy is altered or missing, or they may report foot pain that began after their pelvic pain. Since the feet lie next to the genitals on the homunculus, it is postulated that this may be the result of homuncular smudging.

Gentle guided movements such as pelvic tilts, move- ment of the ischial tuberosities, and guided sensory training in various sitting, standing, and lying postures may be useful for increasing sensory awareness.47,48

Body map training may be used to address the neuromatrix by modifying fear con- ditioning, teaching neutral alignment, reorganizing the sensorimotor cortex, and changing awareness of body parts.39,40,51

There are approximately 200 inhibitory neurons descending from the brain that help downregulate the sensitive nervous system for every one nocicep- tive or danger neuron traveling up to the brain.16

The activity in descending pathways is not constant and can be modulated.52 Decreasing levels of vigilance, attention, and stress are some techniques that may enhance the activity in the descending pathways.12,21 Decreasing a stress response may also help to decrease the sympathetic nervous system response.

Treatment options may include the following:
• Connective tissue mobilization: Mobilization of the soft tissue is used to have a direct effect on tis- sue dysfunction, given the basic need of muscles, fascia, and neural tissue to move in order to be healthy.3,53 Connective tissue mobilization may also directly impact the state of the autonomic nervous system, specifically by interrupting the viscera-somatic reflex arc, which is an autonomic reflex.54 Therefore, connective tissue mobilization may affect both tissue dysfunction and sensitiza- tion through modulation of the nervous system. Clinically, treatment of the connective tissue has been shown to be an important component of tissue dysfunction-based treatment in urologically based pelvic pain.5 It is proposed that this treat- ment may have an important effect not only on local tissue dysfunction but also on the sensitized nervous system.
• Deep breathing: Oxygen is vital for every organ in our body. People with persistent pain tend to have maladaptive breathing patterns, including shallow apical breathing.55 Retraining deep breathing, with both lateral costal and diaphragmatic techniques, is believed to downregulate the sensitive ner- vous system, particularly the sympathetic nervous system.55

• Relaxation training: There are many different styles of relaxation training, including paradoxical relaxation,24 progressive muscle relaxation, auto- genic training, mindfulness training, and medita- tion.56 Research shows that people who meditate have more gray matter in regions of the brain that are important for attention, emotional regu- lation, and mental flexibility.55 Meditation may also decrease anxiety and improve self-esteem.57 Mindfulness training is the skill of maintaining focus on something by choice while allowing thoughts, emotions, and sensations to come in and out of awareness, and at the same time, aware- ness without judgement.56 Patients will respond to different relaxation strategies and a variety of relaxation strategies should be tried to find the best fit. Clinically, patients will gravitate to one form or another, often from personal preference. Allowing a patient to choose her or his preference may help improve compliance.58
• Cardiovascular exercise: There is evidence that aerobic exercise lowers a person’s stress response and assists in mood and anxiety relief.59,60 The American College of Sports Medicine recommends performing moderately intense cardiovascular exercise for 30 minutes per day on at least 5 days per week, or vigorously intense cardiovascular exercise for 20 minutes per day on at least 3 days a week. In addition, the recommendation is that an individual perform 8 to 12 repetitions of 8 to 10 strength training exercises at least twice per week.61
• Guided imagery: Guided imagery allows for individual exploration into belief patterns and movement patterns that may not be helpful in the goal of returning to normal movement and function. These thoughts, beliefs, and move- ments are often outside of conscious awareness and largely outside of one’s control.62 Imagery engages the power of the mind to reduce anxiety, depression, and stress. Carrico et al62 conducted a pilot study, using a guided imagery CD spe- cifically recorded and scripted for women with interstitial cystitis and pelvic pain. The study found that approximately 45% of the treat- ment group participants responded to guided imagery therapy, noting a moderate or marked improvement on the global response assessment. Pain scores and episodes of urgency significantly decreased in the treatment group.

• Yoga: The term yoga is derived from the Sanskrit verb yug, which means to bind or join. This refers to the overarching goal of yoga to unite the mind and body in a way that promotes health.63 Comprehensive protocols have been adapted for yoga in the management of chronic pain. Yoga specifically addresses body awareness through body map training, breathing techniques, and increased awareness of mental and physical states, which may help patients better understand their pain response. Several mechanisms could potential- ly explain the benefits of yoga for persistent pain conditions. Yoga can decrease sympathetic ner- vous system activity, reduce inflammatory mark- ers, reduce stress markers (cortisol), and increase flexibility, strength, circulation, and cardiorespi- ratory capacity.63 Yoga has also been shown to increase the frequency of positive emotions and could potentially undo the physiological effects of negative emotions, broaden cognitive processes, and build physical and psychological resources.63 Finally, it is possible that yoga can lead to improve- ments in self-efficacy for pain control.63
• Affirmations/positive thinking: Patients may be able to learn to control and change their thoughts, seeking mastery in the following areas: stress inoculation, assertiveness in dealing with their sit- uation, handling conflict that arises around their pain, and decreasing their resistance to get bet- ter.64 Thoughts are nerve impulses, and negative thinking alone may drive persistent pain states. Moseley et al65 demonstrated that the thought of movement alone was sufficient to increase pain and swelling in CRPS. The contribution to persis- tent pain states from thoughts and beliefs provides a significant possibility for therapeutic interven- tion. Clinicians can assist and encourage the use of positive affirmations and can demonstrate good modeling of these techniques.
• Joy/laughter: Ongoing stress, particularly in the absence of positive coping skills, lowers resistance, weakens the immune system, and increases suscep- tibility to health problems.66 Pain is reduced while undergoing functional magnetic resonance imag- ing by positive pictures, beautiful music, positive expectations, enticing smells, sweet tastes, social touch, and sexual behavior.67 Patient instruction may include choosing a positive environment for exercise, one that is interesting, novel, and fun.

• Addressing sleep dysfunction: A systematic review concluded that there is consistent evidence asso- ciating chronic low back pain with greater sleep disturbances and reduced sleep duration.68 Reid et al69 looked at the efficacy of aerobic physical activity with sleep hygiene education to improve sleep, mood, and quality of life in individuals with chronic insomnia. The study concluded that an aerobic physical exercise program (involving two 20-minute sessions 4 times per week or one 30-minute session 4 times per week) with sleep hygiene education can be very beneficial to patients with insomnia and depressive mood.69

In peripheral neurogenic pain, nerves are sensitized as a result of plastic changes that have occurred within the peripheral nervous system, including the development of abnormal impulse-gen- erating sites.16,17,71-73 Nerves may also be sensitized because of chemical processes from proinflammatory mediators including prostaglandins, serotonin, brady- kinin, cytokines, and macrophages.16,74

Decreasing the sensitivity of the peripheral nerves may be addressed mechanically through a variety of manual therapy techniques that propose to unload the nerve by increasing the space or fluid motion in the tis- sues around the nerve.2,17,18,24 With decreased tension of the soft tissues surrounding the nerves including muscles, connective tissue, scar tissue, and abnormal joint mechanics, the nerve has a better chance of moving well within the space surrounding it.

A neurodynamic assessment includes physical pal- pation of the nerve where possible, as well as passive and active neurodynamic tests.16,70 For the pelvis, this involves the pudendal, ilioinguinal, iliogastric, femoral, and obturator branches of the lumbosacral nerves.

The pudendal nerve can also be mobilized through various depths of squatting with modifying the neck position to load and unload the dura mater and the nervous system. (See Appendix A.)

Once tissue dysfunction, central sensitization, and neurodynamics have been addressed and are showing signs of improvement, patients need to establish short- and long-term goals to help reduce the threat of increased function. The patient may be asked to create a list of pain control strategies that they can use to pace activities.

Hebb93 described the neurologic basis of motor learning as “Neurons that fire together, wire together. Neurons that fire apart, stay apart.” This is the key concept in using graded motor imagery in retraining the sensitive nervous system. By practicing the skill first through imagery and then progressing to actual movement, there is a change in the representation of the movement and the involved body parts in the sen- sory and motor cortices.46,94 Notably, this can be done without triggering a protective pain response that will help restore normal sensitivity to the nervous system.