neurodynamic, nervous system mobilization, neural mobilization에 관한 생체역학적 근거 - 정리중

[문형철]

압박된 신경, 손상된 신경, 염증이 발생한 신경이 최적으로 재생되기 위한 조건은 무엇일까?

이 질문에 대한 해답찾기다.

neupraxia의 기전

신경 압박(mechanical or chemical stimuli) -> venous congestion -> intraneural circulation and axoplasmic flow 방해 -> 이어지는 hypoxia와 microvascular permeability의 변경 -> 신경의 inflammatory response -> subperineurial edema -> endoneurial fluid pressure의 증가

panic bird....

neurobiology, neurodynamics and clinical evidence.pdf

Abstract

Peripheral neuropathic pain is the term used to describe situations where nerve roots or peripheral nerve trunks have been injured by mechanical and/or chemical stimuli that exceeded the physical capabilities of the nervous system. Clinical manifestations of peripheral neuropathic pain are often discussed in terms of positive and negative symptoms. Positive symptoms reflect an abnormal level of excitability in the nervous system and include pain, paresthesia, dysesthesia, and spasm. Negative symptoms indicate reduced impulse conduction in the neural tissues and include hypoesthesia or anesthesia and weakness. 

It is proposed that conservative management incorporating neurodynamic and neurobiology education, nonneural tissue interventions, and neurodynamic mobilization techniques can be effective in addressing musculoskeletal presentations of peripheral neuropathic pain. 

While a small amount of clinical evidence lends some support to this proposal, much more clinical research is necessary to identify those patients with peripheral neuropathic pain that will respond most favorably to neurodynamic mobilization techniques and clarify specific treatment parameters that will be most effective. 

Regardless of the results of this future research, conservative care will always need to be based on sound clinical reasoning so that interventions can be individualized to address the nuances of each patient’s presentation of peripheral neuropathic pain.

1. Introduction

Neural tissues are well equipped to tolerate mechanical forces generated during the positions or movements associated with daily and sport activities (Butler, 1991, 2000; Sunderland, 1990, 1991). Peripheral neuropathic pain is the term used to describe situations where nerve roots or peripheral nerve trunks have been injured by mechanical and/or chemical stimuli that exceeded the physical capabilities of the nervous system (Butler, 2000; Gifford & Butler, 1997;Merskey & Bogduk, 1994). 

In addition to well recognized radiculopathies and nerve entrapments, peripheral neuropathic mechanisms may have a role in some presentations of other musculoskeletal syndromes commonly seen in sport, such as lateral epicondylalgia (Izzi, Dennison, Noerdlinger, Dasilva, & Akelman, 2001; Yaxley & Jull, 1993), achilles tendinosis (Hirose & McGarvey, 2004; McCrory, Bell, & Bradshaw, 2002), heel pain (Meyer, Kulig, & Landel, 2002; Schon, Glennon, & Baxter, 1993; Shacklock, 1995a), and inversion ankle sprains (Pahor & Toppenberg, 1996). 

The goal of this masterclass paper is to review the neurobiological mechanisms associated with musculoskeletal presentations of peripheral neuropathic pain and offer management ideas that integrate neurobiology, neurodynamics, and clinical evidence.

2. Clinical presentation

2.1. Symptomatic complaints

다른 논문 도표 

Neurogenic Pain. Diagnosis and Treatment.pdf

Clinical manifestations of peripheral neuropathic pain are often discussed in terms of positive and negative symptoms. Positive symptoms reflect an abnormal level of excitability in the nervous system and include pain, paresthesia, dysesthesia, and spasm. Negative symptoms indicate reduced impulse conduction in the neural tissues and include hypoesthesia or anesthesia and weakness (Baron, 2000; Devor & Seltzer, 1999; Hall & Elvey, 1999; Harden, 2005; Woolf, 2004; Woolf & Mannion, 1999).

Painful sensations associated with peripheral nerve injury involve some combination of nerve trunk pain and

dysesthetic pain (Asbury & Fields, 1984). Nerve trunk pain is typically described as a deep and aching sensation that has been attributed to increased activity from mechanically or chemically sensitized nociceptors in the connective tissue sheaths of the nervous system (i.e. nervi nervorum and sinuvertebral nerves) (Asbury & Fields, 1984; Bove & Light,

1997; Edgar & Nundy, 1966; Hromada, 1963; Kallakuri, Cavanaugh, & Blagoev, 1998). 

Dysesthetic pain is often characterized as an unfamiliar or abnormal sensation such as burning, tingling, electric, searing, drawing, or crawling (Asbury & Fields, 1984), and it is thought to be the result of volleys of impulses originating from damaged or regenerating afferent fibers that have become hyperexcitable (i.e. abnormal impulse generating sites) (Asbury & Fields, 1984; Baron, 2000; Devor & Seltzer, 1999; Woolf, 2004; Woolf & Mannion, 1999). Nerve trunk pain and dysesthetic pain may be stimulus evoked, meaning that they are experienced as exaggerated responses to mechanical, chemical, or thermal stimuli (Asbury & Fields, 1984; Baron, 2000; Devor & Seltzer, 1999; Hall & Elvey, 1999; Harden, 2005; Woolf & Mannion, 1999). 

Hyperalgesia describes an exaggerated pain response produced by a normally painful stimulus, and allodynia characterizes a pain response created by a stimulus that would not usually be painful (Merskey & Bogduk, 1994). Movements or positions that expose sensitized neural tissues to compressive, friction, tensile, or vibration stimuli can be symptomatic for patients experiencing a musculoskeletal presentation of peripheral neuropathic pain, and these  phenomena would be described as mechanical hyperalgesia/allodynia (Gifford, 2001; Gifford & Butler, 1997; Hall & Elvey, 1999; Johnson, 1997; Merskey & Bogduk, 1994).

While nerve trunk pain commonly has a fairly direct relationship to aggravating stimuli (Asbury & Fields, 1984; Hall & Elvey, 1999), dysesthetic pain can exhibit a variety of clinical behaviors (Butler, 2000; Devor & Seltzer, 1999; Gifford, 2001; Gifford & Butler, 1997). Patients may experience a burst of pain that coincides with the onset of the stimulus but subsides prior to the stimulus being removed. An example could involve a tennis player with peripheral neuropathic neck-arm pain experiencing a stab of pain when initiating cervical extension at the start of the ball toss for a serve and reporting that this sensation subsides even with further movement into extension to view the ball at the peak of the toss just prior to racquet contact. Symptoms provoked by movement may persist well after the stimulus has been removed and the patient has stopped the offending activity (i.e. hyperpathia). 

Dysesthetic pain may sometimes be a response to the cumulative effect of several stimuli. For example, the tennis player described above with peripheral neuropathic neck-arm pain may not report the provocation of symptoms until after hitting multiple shots during a rally where the cervical spine has moved repeatedly relative to the trunk. 

Additionally, patients may occasionally experience stimulus-independent or spontaneous pain that may be paroxysmal in nature, or they may report that symptoms are worse during times of increased life stress. These perversions in the direct

stimulus-response relationship are a reflection of a hyperexcitable nervous system displaying properties of increased afferent discharge from abnormal impulse generating sites (AIGS) (Baron, 2000; Devor & Seltzer, 1999; Harden, 2005; Woolf & Mannion, 1999). In spite of this variability, peripheral neuropathic pain associated with musculoskeletal disorders will generally exhibit a relatively consistent stimulus-response relationship (Butler, 2000; Gifford & Butler, 1997; Hall & Elvey, 1999).

Although commonly approximating dermatomes, cutaneous fields, or paths coursed by nerve trunks, the distribution of peripheral neuropathic pain associated with musculoskeletal dysfunction can also be variable (Butler, 2000; Gifford & Butler, 1997). Bove, Zaheen, and Bajwa (2005) stated that dermatomal charts may not be most appropriate for diagnosing lower limb radicular pain, because their sample of 25 patients with lumbar radiculopathy reported that symptoms experienced at rest or during passive straight leg raise (SLR) were deep in nature. 

The authors recommended that myotomal or sclerotomal charts may be more helpful in the diagnostic process. In patients with cervical nerve root irritation (i.e. no conduction deficit), Slipman et al. (1998) found that nearly 40% of symptomatic C6 nerve roots stimulated under fluoroscopy exhibited referred symptoms in the ulnar aspect of the hand.

Variability in symptom location is partly related to the fact that the nervous system is a continuous tissue complex

(Butler, 1991, 2000). Sensory and motor fibers display intradural connections between adjacent spinal cord segments (Tanaka, Yoshinori, An, Ikuta, & Yasuda, 2000), which means that neural injury near the intervertebral foramen can affect nerve fibers associated with more than one spinal cord level. Central nervous system neurons become sensitized after peripheral nerve injury and expand their receptive fields (Baron, 2000; Costigan & Woolf, 2000; Devor & Seltzer, 1999; Harden, 2005; Hasue, 1993; Mannion & Woolf, 2000; Woolf & Mannion, 1999), a process that can also explain why peripheral neuropathic symptoms may spread beyond typical dermatomal and cutaneous field boundaries (Butler, 2000; Gifford, 2001; Gifford & Butler, 1997; Shacklock, 1999).

2.2. Physical examination findings

A comprehensive assessment of any patient complaint requires examination of both nonneural and neural tissues. Physical signs of peripheral neuropathic pain secondary to musculoskeletal dysfunction include increased mechanosensitivity in neural tissues combined with relevant impairments in surrounding musculoskeletal structures,

and the severity of the injury dictates whether deficits in impulse conduction are present (Butler, 2000; Elvey, 1997;

Gifford & Butler, 1997; Hall & Elvey, 1999). Specific concepts related to examination of nonneural structures and impulse conduction in neural tissues are beyond the scope of this paper and can been reviewed in any number of texts (e.g. Cyriax, 1982; Magee, 2002; Petty & Moore, 2001). This section focuses on physical examination findings that are indicative of increased neural tissue mechanosensitivity.

Neurodynamic tests (e.g. slump test, straight leg raise, upper limb neurodynamic tests) challenge the physical capabilities of the nervous system by using multijoint movements of the limbs and/or trunk to alter the length and

dimensions of the nerve bed surrounding corresponding neural structures (Beith, Robins, & Richards, 1995; Butler,

1991, 2000; Coppieters, Stappaerts, Everaert, & Staes, 2001; Elvey, 1979, 1997; Hall & Elvey, 1999; Millesi, Zoch, & Rath, 1990; Shacklock, 1995b). Guidelines have been proposed to assist clinicians in identifying a ‘positive’ response to a neurodynamic test that would be considered suggestive of increased mechanosensitivity in neural tissues.

First, the test reproduces the patient’s symptoms or associated symptoms, and movement of a body segment

remote from the location of symptoms provoked in the neurodynamic test position alters the response (i.e. structural differentiation). Second, there are differences in the test response between the involved and uninvolved sides

or variations from what is known to be a normal response in asymptomatic subjects. 

These differences may include asymmetries in sensory response (i.e. aching, pulling, burning, tingling, etc.), range of motion, or resistance perceived by the examiner during application of the neurodynamic test, and these asymmetries are also altered by appropriate structural differentiation (Butler, 1991, 2000; Butler & Gifford, 1989a; Elvey, 1997; Shacklock, 2005). In some situations, the clinician may not be able to rely on asymmetry between limbs as a criterion for determining a ‘positive’ neurodynamic test. 

This can be illustrated in patients experiencing neck and/or arm symptoms after motor vehicle accident exhibiting hyperalgesic responses to neurodynamic testing in both upper limbs, an observation hypothesized to reflect the presence of central sensitization (Sterling, Treleaven, & Jull, 2002).

Alteration in resistance perceived by the examiner during neurodynamic testing is considered one of the most important signs of increased neural tissue mechanosensitivity (Hall & Elvey, 2004). Resistance perceived by the examiner is not necessarily a reflection of the viscoelastic behavior of the nervous system and its associated connective tissues. Protective muscle activity from the upper trapezius, brachialis, and biceps contributes to resistance encountered by the examiner during a median biased upper limb neurodynamic test (ULNT) (Balster & Jull, 1997; Jaberzadeh, Scutter, & Nazeran, 2005; van der Heide, Allison, & Zusman, 2001). 

그림) ULNT방법

Similar activity from the hamstrings is associated with the resistance encountered during straight leg raise in asymptomatic and symptomatic subjects (Hall, Zusman, & Elvey, 1998). In contrast, changes in knee extension mobility secondary to releasing the neck flexion component of the slump test are not associated with changes in hamstring activity in asymptomatic subjects (Lew & Briggs, 1997).

The presence of a ‘positive’ neurodynamic test does not enable the clinician to identify the specific site of neural

tissue injury; it merely indicates that the entire neural tissue tract loaded during the test is exhibiting an increased amount

of mechanosensitivity (Butler, 2000). Neural tissues respond to movement through the development of strain, excursion,

and stress in a non-uniform fashion (Grewal, Xu, Sotereanos, & Woo, 1996; Millesi, Zoch, & Reihsner, 1995; Phillips,

Smit, DeZoysa, Afoke, & Brown, 2004; Shacklock, 1995b). Consequently, neural structures will be subjected to different

mechanical loads depending upon the order of joint movement during neurodynamic testing (Butler, 2000; Shacklock,

1995b), and the testing sequence has been shown to alter the mobility and/or symptom response during straight leg raise

(Boland & Adams, 2000; Butler, 1991), slump (Johnson & Chiarello, 1997; Maitland, 1979, 1985; Pahor&Toppenberg,

1996), and a median nerve biased ULNT (Coppieters et al., 2001). 

The greatest mechanical challenge for a segment of neural tissue is thought to occur when the joint adjacent to the nerve is loaded first during the testing sequence, and the development of strain, excursion, and stress will spread to other portions of the neural tissue tract as more joint complexes participate in the movement (Shacklock, 1995b). The concept of neurodynamic sequencing may assist in determining whether a musculoskeletal peripheral neuropathic problem is in a more proximal or distal segment of the affected neural structure. The sequence of dorsiflexion and eversion prior to straight leg raise may be more effective for detecting a peripheral neuropathic component to heel pain (Meyer et al., 2002; Shacklock, 1995a). 

Applying a median nerve biased ULNT in a proximal to distal sequence has been shown to have clinical value for ruling out the presence of electrodiagnostically confirmed cervical radiculopathy (Wainner et al., 2003), but this same testing sequence was not helpful in identifying electrodiagnostically confirmed carpal tunnel syndrome (Wainner et al., 2005). The ultimate diagnostic value of neurodynamic sequencing needs to be ascertained by further validation studies, but until that time, clinicians may enhance their ability to detect relevant signs of increased neural tissue mechanosensitivity by altering the neurodynamic testing sequence to replicate the order of movement used by patients during symptomatic activities(Butler, 2000).

Nerve trunk palpation (with or without sustained manual compression) and isometric contraction (e.g. resisted isometric pronation as the elbow is gradually extended targets the median nerve interface with the pronator teres) are other physical examination maneuvers used to identify enhanced mechanical sensitivity in neural structures (Butler, 2000; Elvey, 1997; Hall & Elvey, 1999; Novak & Mackinnon, 2005). Increased afferent discharge from AIGS and sensitized nervi nervorum are thought to mediate the symptom response associated with these provocative tests (Butler, 2000; Devor & Seltzer, 1999; Hall & Elvey, 1999).

Provocation of symptomatic complaints during nerve palpation does not necessarily identify the site of neural tissue injury, because the entire neural tissue tract can become mechanically sensitive after injury to a particular nerve segment (Butler, 2000; Hall & Elvey, 1999). For example, uninjured portions of the tibial nerve in the popliteal fossa or posterior to the medial malleolus may be more sensitive to palpation in a patient with a low lumbar radicular problem. This spread of mechanosensitivity to uninjured portions of the involved neural tissue tract may be due to changes in axoplasmic flow and altered concentrations of ion channels that dictate the excitability and firing properties of affected nerve fibers (Butler, 2000; Devor & Seltzer, 1999), and nervi nervorum outside of the region of neural injury can become more sensitive to mechanical and chemical stimuli (Bove & Light, 1997; Elvey, 1997; Hall & Elvey, 1999). Additionally, hyperalgesic/allodynic responses in uninjured neural tissues may be the result of alterations in central nervous system processing of afferent information (i.e. central sensitization) (Butler, 2000; Devor & Seltzer, 1999; Gifford & Butler, 1997; Hall & Elvey, 1999; Shacklock, 1999; Zusman, 1992). 

In order to be more confident that a site of neural injury has been identified, the clinician should detect changes in tissue quality of the palpated nerve segment and adjacent nonneural structures in addition to any hyperalgesic/allodynic responses. Positional testing of the spine or limbs may also impose mechanical loads on the nervous system by reducing the space available for corresponding neural structures (e.g. extension or ipsilateral side-bending of the spine at the intervertebral foramina, Phalen’s wrist flexion test at the carpal tunnel) (Farmer & Wisneski, 1994; Fujiwara, An, Lim, & Haughton, 2001; Gifford, 2001; Kitagawa et al., 2004; Novak & Mackinnon, 2005; Nuckley, Konodi, Raynak, Ching, & Mirza, 2002). These provocative tests provide evidence of increased mechanosensitivity in sensitized neural tissues through the same mechanisms discussed for palpation (i.e. nervi nervorum, AIGS, central sensitization).

In more minor peripheral neuropathic problems, some of the examination procedures described above may need to be combined to provide an adequate mechanical stimulus to detect alterations in neural tissue sensitivity. Examples might include palpating the superficial branch of the fibular nerve in a neurodynamically loaded position of straight leg raise with ankle plantarflexion and inversion, or adding sustained compression over the transverse carpal ligament with the wrist in a flexed position (i.e. carpal compression test with wrist flexion) (Butler, 2000; MacDermid & Wessel, 2004; Novak & Mackinnon, 2005). 

The therapist needs to use sound clinical reasoning skills to ensure that the vigor of the physical examination is appropriate for the suspected level of reactivity of the problem (Butler, 2000; Hall & Elvey, 1999; Shacklock, 2005). As mentioned previously, the identification of relevant impairments in surrounding nonneural structures will point to a musculoskeletal cause of the peripheral neuropathic pain problem. The clinical behavior of musculoskeletal peripheral neuropathic pain will typically reflect a fairly direct stimulus-response relationship during the physical examination, but it can exhibit some of the aforementioned perversions in this relationship (e.g. burst of pain that stops prior to removal of the stimulus, persistence of pain after stimulus removed, onset of pain only after cumulative effect of several movements) (Butler, 2000; Gifford, 2001; Gifford & Butler, 1997). Additionally, all of the physical examination findings should be consistent with subjective examination information that revealed the features of the symptomatic complaint and its history (Butler, 2000; Elvey, 1997; Hall & Elvey, 1999). The subjective and physical examination findings thought to be associated with musculoskeletal presentations of peripheral neuropathic pain have been summarized in Box 1.

Box 1. Clinical features proposed to be associated with musculoskeletal peripheral neuropathic pain. Any combination of features may occur in the patient’s presentation of symptoms. Please refer to text for details

† Superficial burning, stinging and paresthesia (i.e. dysesthetic pain)

† Distribution of symptoms may approximate peripheral cutaneous or dermatomal zones

† Deep aching, cramping (i.e. nerve trunk pain)

† Distribution of ‘deep’ symptoms may approximate myotomal or sclerotomal zones and/or pathways of involved nerve

trunks

† Antalgic postures that correspond to unloading of sensitive neural tissues

† Active movement impairment

† Passive movement impairment that corresponds with active movement impairment

† Symptoms mechanically evoked by nerve compression and/or tension of appropriate neural structures that relate to

active and passive movement impairments (perversions in this direct stimulus-response relationship may be present)

† Motor and/or sensory impairments that correspond to distribution of symptoms

† In ongoing problems, often difficult to ease symptoms for any length of time with rest or medications

† In ongoing problems, pain may behave as if having ‘a mind of its own’

3. Neurobiological mechanisms

Mechanical and chemical irritation can lead to musculoskeletal neural tissue injury. Repetitive compressive, tensile, friction, and vibration forces acting near anatomically narrow tissue spaces through which neural structures pass can cause mechanical irritation (Butler, 1991; Sunderland, 1991). Injured somatic tissues adjacent to nerve structures release inflammatory substances that can chemically irritate neural tissues (Cavanaugh, 1995; Garfin,

Rydevik, & Brown, 1991; Garfin, Rydevik, Lind, & Massie, 1995; Murata, Rydevik, Takahashi, Larsson, & Olmarker,

2005; Takahashi, Yabuki, Aoki, & Kikuchi, 2003; Takebayashi, Cavanaugh, Ozaktay, Kallakuri, & Chen, 2001). Pathophysiological and pathomechanical responses to nerve injury affect the vascular, connective tissue, and impulse conducting tissue components of the nervous system and lead to the neurobiological mechanisms responsible for

the positive and negative symptoms associated with musculoskeletal peripheral neuropathic pain.

3.1. Sensitization of neural connective tissue nociceptors

Compromise in intraneural circulation appears to be the first step in the pathophysiological cascade of nerve injury. Mechanical or chemical stimuli that exceed the physical capabilities of neural tissues induce venous congestion, and therefore, impede intraneural circulation and axoplasmic flow (Greening & Lynn, 1998; Hasue, 1993; Kobayashi, Yoshizawa, & Nakai, 2000; Lundborg & Dahlin, 1992; Ogata & Naito, 1986; Olmarker & Rydevik, 1991; Parke &

Whalen, 2002; Rempel, Dahlin, & Lundborg, 1999; Rydevik, Brown, & Lundborg, 1984). Subsequent hypoxia and alterations in microvascular permeability cause an inflammatory response in nerve trunks and dorsal root

ganglia (DRG) that leads to subperineurial edema and increased endoneurial fluid pressure (Hasue, 1993; Igarashi,

Yabuki, Kikuchi, & Myers, 2005; Kobayashi et al., 2000; Lundborg, 1988; Lundborg, Myers, & Powell, 1983; Mackinnon, Dellon, Hudson, & Hunter, 1984; O’Brien et al., 1987; Parke & Whalen, 2002; Rempel et al., 1999; Rydevik, Myers, & Powell, 1989; Triano & Luttges, 1982; Yabuki, Onda, Kikuchi, & Myers, 2001). 

- 신경 압박(mechanical or chemical stimuli) -> venous congestion -> intraneural circulation and axoplasmic flow 방해 -> 이어지는 hypoxia와 microvascular permeability의 변경 -> 신경의 inflammatory response -> subperineurial edema -> endoneurial fluid pressure의 증가

Neuropeptides released from mechanically irritated nervi nervorum and pro-inflammatory mediators produced by immune cell activation contribute to this inflammatory response (Gazda et al., 2001; Sauer, Bove, Averbeck, & Reeh, 1999; Watkins

& Maier, 2004). Once neural connective tissues are inflamed, nociceptors in the nervi nervorum and sinuvertebral

nerves will become sensitized to mechanical and chemical stimuli, contributing to the enhanced mechanosensitivity

observed in peripheral neuropathic pain (i.e.nerve trunk pain) (Baron, 2000; Bove & Light, 1997; Devor & Seltzer, 1999; Gifford & Butler, 1997; Greening & Lynn, 1998; Hall & Elvey, 1999; Kallakuri et al., 1998; Zochodne,1993).

- neuropeptide 분비, 염증반응

- 일단 neural connective tissue가 염증이 발생하면 신경의 감작이 발생

Endoneurial edema persists because the perineurial diffusion barrier does not allow inflammatory exudates to escape (Lundborg, 1988; Lundborg & Dahlin, 1992; Lundborg et al., 1983; Murphy, 1977). Persistent endoneurial edema leads to intraneural fibrosis and compromises the viscoelastic properties of neural connective tissues (Beel, Groswald, & Luttges, 1984; Millesi et al., 1995; Rempel et al., 1999). When intraneural fibrosis has reduced the extensibility of neural connective tissues, already sensitized nociceptors in the nervi nervorum and sinu-vertebral nerves will be subjected to more intense mechanical stimulation, because fibrotic connective tissues can no longer effectively attenuate the mechanical loads associated with daily and sport activities, or physical examination maneuvers (Bove & Light, 1997; Millesi et al., 1995; Sunderland, 1990). Consequently, intraneural fibrosis can further contribute to increased nociceptive input from nervi nervorum and sinuvertebral nerves in peripheral neuropathic pain states. 

- endoneurial edema가 지속되면 intraneural fibrosis가 유발되고, neural connective tissue의 점탄성이 손상. 

- intraneural fibrosis가 neural connective tissue의 신장성을 감소시킬때, 이미 감작된 신경은 기계적 자극에 좀더 민감해짐. 

참고) nervi nervorum

말초신경의 결합조직 막에 분포하는 감각신경섬유를 nervi nervorum이라 하며 이는 신경에 혈액공급을 하는 혈관벽에도 분포한다. 이러한 nervi nervorum 또한 말초신경의 질환이 있을 때 통증의 원인이 될 수 있으며, 조직학적 연구에서 대상포진 감염 후

수개월이 지난 후에도 신경섬유에서 염증반응세포들을 발견할 수 있다

참고) The Sinuvertebral Nerve: A nerve of mystery

The Sinuvertebral Nerves (SN), is a mixed nerve as well. It carries both autonomic fiber (sympathetic) and sensory (afferent) fiber. The sensory portion, which has the capability to carry the feeling of PAIN, arises from the outer 1/3 of the posterior anulus fibrosus (yellow balls) and PLL (#7). It then spilts and attaches to both the dorsal ramus and the grey ramus communicans, although this nerves anatomy and course seems to be quite anomalous.

Of importance is the fact that if irritated, the nerve ending within the disc have the potential to generate both back pain and/or lower limb pain (Discogenic Pain). This lower limb pain-referral has been greatly studied by Ohnmeiss et al. and is quite an interesting phenomenon. Discogenic Sciatica is the term I have given this referred discogenic pain. It is believed that the sinuvertebral nerve-endings are 'sensitive' to the irritating effects of degenerated nucleus pulposus, that may be introduced into the outer region of the anulus from a grade three anular tear. (see may pages on Anular Tears for more information.)

Amazingly, the sinuvertebral nerve also innervates (connects to) the disc above and below! So, the sinuvertebral nerve of the L4 disc also innervates the L5 and L3 disc. This may help explain why a L4 disc herniation/anular tear may clinically present with some signs of L5 and/or L3 involvement as well. It also carries autonomic nerve fiber to the blood vessels (not shown) of the epidural space. Sympathetic nerves control how the blood vessels function (vasomotor & vasosensory).

 Although rare, injury to these sympathetic nerves may cause RSD symptoms in the patients lower limbs; this usually would occur following surgery. (This may explain why I have a very slight case of RSD in my left foot following surgery - since my doc spent an hour cutting his way through a 'nest' of epidural vessels during my micro-discectomy)

The exact pain-pathway (how pain travels from the disc to the spinal cord) of discogenic pain is another fascinating and controversial subject. It seems that the sensory pathway from the sinuvertebral nerves into the spinal cord, does NOT take the 'expected' route in every patient. Some research (101) has demonstrated that pain-signals travel from the disc, re-enter the IVF (via sinuvertebral nerve) and DRG at the SAME level. Other, more recent research has indicated that pain-signals travel from the disc, through the sinuvertebral nerve, through the Gray Rami Communicans, into theSympathetic Trunk (ST), up the sympathetic chain to the L2 vertebral level (yes I said L2), through the gray rami communicans, into the L2 dorsal rami, into the L2 IVF, and into the L2 DRG (80, 81). The latter pain pathway is why some investigators believe that lower level disc herniations may present as L2 dermatomal pain (groin region) in some patients! 

To drive-home my point that the pain path from the disc does NOT always re-enter at the same vertebral level, I present the 2004 randomized controlled investigation by Oh and shim (26). In an incredibly well designed outcome study, the latter investigators demonstrated that by 'cutting' (RF neurotomy) the Gray Ramus Communicans, the majority of chronic discogenic pain sufferers achieved substantial relief of their pain and avoid fusion surgery. (26) This proves that at least some of the incoming pain signals were traveling toward the sympathetic trunk (which is on the anterior side of the vertebra) and NOT re-entering the spinal nerves at the same level.

3.2. Formation of abnormal impulse generating sites (AIGS)

An injured segment of peripheral nerve and its associated DRG may develop the ability to repeatedly generate their own impulses (Devor & Seltzer, 1999). They are referred to as AIGS, because these portions of a sensory neuron do not

normally initiate impulses (Devor & Seltzer, 1999). The main features of AIGS are mechanosensitivity, chemosensitivity,

and spontaneous firing (Butler, 2000; Devor & Seltzer, 1999).

Ion channels are proteins produced in the cell body that insert into the axon membrane and determine neuron excitability. The ensemble of ion channels is normally remodeled on a continual basis so that an afferent neuron maintains an appropriate level of sensitivity to surrounding stimuli (Bear, Connors, & Paradiso, 2001; Costigan & Woolf, 2000; Devor & Seltzer, 1999; Koester & Siegelbaum, 1995). Nerve injury alters gene expression‎ within the cell body (Baron, 2000; Costigan & Woolf, 2000), which means that the type and number of ion channels in the axon membrane change so that neurons fire more readily in response to mechanical and chemical stimuli (Baron, 2000; Devor & Seltzer, 1999; Harden, 2005; Woolf & Mannion, 1999). Impairments in axoplasmic flow lead to the accumulation of ion channels in areas of nerve

injury (Devor & Seltzer, 1999). Since ion channels insert into portions of the axon membrane not covered by myelin, DRG, areas of myelin thinning, and areas of segmental demyelination provide additional opportunities for the abnormal accumulation of mechanosensitive and chemosensitive ion channels (Amir & Devor, 1993; Calvin, Devor, & Howe, 1982; Chen & Devor, 1998; Devor & Seltzer, 1999). All of these areas are now capable of generating an increased amount of nociceptive input that contributes to the symptoms and signs of musculoskeletal peripheral neuropathic pain (i.e. dysesthetic pain).

The type and number of ion channels dictate which stimuli will evoke symptoms in musculoskeletal peripheral neuropathic pain. Normally innocuous lengthening, pinching, or friction forces become capable of provoking symptoms when concentrations of mechanosensitive ion channels are increased. Repetitive movement (e.g. soccer player with lower extremity peripheral neuropathic pain provoked with running) or sustained positioning (e.g. cyclist that aggravates upper extremity peripheral neuropathic symptoms with arms in certain positions on the handlebars) can evoke symptoms from AIGS packed with ischemosensitive channels, and inflammatory chemicals from injured neural or nonneural tissues can stimulate chemosensitive channels (Butler, 2000; Devor & Seltzer, 1999; Gifford, 2001; Gifford & Butler, 1997). Emotional stress can exacerbate symptoms of nerve injury (Butler, 2000; Gifford, 2001), partly because the chemicals associated with stress (e.g. adrenaline, noradrenaline) are capable of stimulating AIGS (Baron, 2000; Devor & Seltzer, 1999; Greening & Lynn, 1998; Hasue, 1993; Shacklock, 1995b). 

AIGS also exhibit spontaneous activity (Devor & Seltzer, 1999), which corresponds to patient reports that symptoms sometimes occur independent of any type of stimulus (Gifford, 2001; Gifford & Butler, 1997). Axonal mechanosensitivity and spontaneous discharge secondary to neural inflammation appear to develop primarily in A-delta and C fibers that innervate deep structures (Bove, Ransil, Lin, & Leem, 2003), which may provide a partial explanation for the aforementioned observation that musculoskeletal peripheral neuropathic pain is often described as deep in nature (Bove et al., 2005).

When the mid-portion of afferent axons or DRG generate their own impulses, the messages travel toward the spinal

cord and toward the periphery. Impulses in afferent neurons that travel toward the periphery are referred to as antidromic

impulses. Upon reaching the peripheral terminals of afferent neurons, antidromic impulses cause the release of  proinflammatory chemicals into the target tissue, a process referred to as neurogenic inflammation (Daemen et al.,

1998; White, 1997). Therefore, an injured segment of neural tissue can have a detrimental impact on the physical health

of the target tissue it innervates (Butler, 2000; Shacklock, 1995a). The process of neurogenic inflammation accounts

for the earlier statement that peripheral neuropathic pain may have a role in some presentations of musculoskeletal

syndromes such lateral epicondylalgia, achilles tendinosis, heel pain, and inversion ankle sprains.

3.3. Central sensitization and the neuromatrix

As mentioned previously, augmentation of sensory processing within the central nervous system (i.e. central sensitization) can contribute to the distribution and stimulus-response behavior of musculoskeletal peripheral neuropathic pain. Central sensitization develops because of alterations in afferent input, changes in chemicals transported from the periphery, sprouting of low threshold afferent fibers into superficial layers of the dorsal horn involved in nociception, immune activation, and alterations in central descending control mechanisms (i.e. disinhibition) (Baron, 2000; Gracely, Lynch, & Bennett, 1992; Harden, 2005; Nakamura & Myers, 2000; Rutkowski, Winkelstein, Hickey, Pahl, & DeLeo, 2002; Wall, 1991; Watkins & Maier, 2004; Woolf, 2004; Woolf & Mannion, 1999). An appreciation of the latter is important for

understanding that the brain is not a passive recipient of afferent information (Melzack, 1996, 2005); it actively modifies the input it receives through descending control mechanisms (Shacklock, 1999).

A recent definition of pain acknowledges the active role the brain has in any clinical pain state. Pain is produced by the brain when it perceives that body tissues are in danger and a response is required (Moseley, 2003a). Areas of the brain associated with sensory perception, emotion, attention, cognition, and motor planning are activated during a pain experience (Butler, 2000; Melzack, 1996, 2005; Moseley, 2003a; Vogt, 2005), and this neural circuitry has been referred to as the pain neuromatrix (Melzack, 1996, 2005; Moseley, 2003a). 

The multiple brain areas involved in the pain neuromatrix provide a partial explanation for why psychosocial issues such as distress, mistaken beliefs about the nature of the pain, and fear of activity or reinjury can exacerbate pain and slow recovery (Butler, 2000; Main & Watson, 1999; Moseley, 2003a; Shacklock, 1999; Vlaeyen & Linton, 2000; Zusman, 2002). An understanding of the pain neuromatrix can expand the options available to the therapist in the management of musculoskeletal peripheral neuropathic pain, because it underscores the need to address the patient’s pain behavior and distress in addition to the nociceptive component of the problem (Butler, 2000; Main & Watson, 1999; Moseley, 2003a; Shacklock, 1999).

3.4. Impairment of impulse conduction

In addition to leading to intraneural fibrosis, the amount and duration of endoneurial edema is directly correlated with more marked degradation in myelin content and axon structure (Rempel et al., 1999). It has been hypothesized that these myelin changes are consequences of impaired axoplasmic flow and altered function of the cell body (Dahlin, Nordborg, & Lundborg, 1987). There will be varying degrees of pathology present in adjacent fascicles within the affected nerve segment (Greening & Lynn, 1998; Mackinnon et al., 1984; O’Brien et al., 1987). Consequently, a patient may report significant peripheral neuropathic pain complaints, but clinical examination of impulse conduction and electrodiagnostic testing may be normal (Mackinnon, 1992). Since electrodiagnostic testing cannot be specific to individual nerve fascicles, normal fascicles account for normal electrodiagnostic tests while adjacent abnormal fascicles and inflamed neural connective tissues can be responsible for symptom complaints (Greening & Lynn, 1998; Mackinnon, 1992). 

It is important for the clinician to appreciate that many patients presenting with musculoskeletal peripheral neuropathic pain may exhibit any combination of the positive symptoms of pain, paresthesia, dysesthesia, and spasm with no clinical

evidence of the negative symptoms of hypoesthesia or anesthesia and  weakness (Butler, 2000; Greening & Lynn,

1998; Hall & Elvey, 1999). In other words, these patients will have a primary presentation of increased neural tissue

mechanosensitivity. A summary of the pathophysiology and neurobiology associated with musculoskeletal peripheral

neuropathic pain is shown in Fig. 1.

4. Management and clinical evidence

The broad goals for managing musculoskeletal presentations of peripheral neuropathic pain are to reduce the 

mechanosensitivity of the nervous system and restore its normal capabilities for movement. The principles of management discussed in the following sections can only be applied within the context of a clinical reasoning framework

where the therapist employs a system of reassessment to judge the impact that intervention strategies have on the nonneural and neural components of the problem (Butler, 1991, 2000; Butler & Gifford, 1989b; Hall & Elvey, 1999; Shacklock, 2005). Relevant clinical evidence from the published literature has been integrated into the discussion.

4.1. Education in neurodynamics and neurobiology

Patients should understand that the nervous system is well designed to move during daily activities, and an introduction to neurobiomechanical concepts can make it easier to explain why certain movements or physical examination maneuvers have become symptomatic. Appreciating the mechanical continuity of the nervous system may also assist patients in understanding why movement of body parts remote from the site of symptoms may be used as a treatment strategy to mobilize neural tissues. The impact movement has on the nervous system is not only mechanical; discussion should include explanations of how intraneural circulation, axoplasmic flow, and nociceptors in neural connective tissues can be affected by mechanical loading (Shacklock, 1995b). The interdependence between the mechanics and physiology of the nervous system is termed neurodynamics (Shacklock, 1995b), and

educating patients in neurodynamic concepts sets a foundation for discussing the aforementioned neurobiological mechanisms associated with the development of musculoskeletal peripheral neuropathic pain.

Educating patients about the neurobiological mechanisms involved in the clinical behavior of their presentation of peripheral neuropathic pain can reduce the threat value associated with their pain experience and alter any unhelpful beliefs they may have about their problem (i.e. may influence emotional and cognitive components of the pain neuromatrix) (Butler, 2000; Moseley, 2003a; Shacklock, 1999). Patients are very capable of understanding information on the neurobiology of pain (Moseley, 2003b), and Butler & Moseley (2003) have detailed a method for explaining this information in patient-friendly language. Evidence exists, for example, that presenting this information to patients with low back pain can make immediate changes in straight leg raise

mobility that correlate directly with reductions in unhelpful beliefs and attitudes about pain (Moseley, 2004). It is proposed that neurobiology education sets a scene within which clinician- or patient-generated therapeutic movement can be more effective (Butler, 2000; Moseley, 2003a; Shacklock, 1999).

4.2. Nonneural tissue impairments

Impairments in nonneural tissues that provide clinical evidence for a musculoskeletal cause of peripheral neuropathic pain need to be addressed during management (Butler, 1991, 2000; Butler & Gifford, 1989b; Hall & Elvey, 1999; Shacklock, 2005). Ensuring that adjacent nonneural structures are functioning in an optimal fashion can reduce the mechanical forces these structures place on sensitive neural tissues (Butler, 2000; Hall & Elvey, 1999), thereby theoretically reducing nociceptive input from sensitized nervi nervorum and AIGS (Butler, 2000). For example, restoring optimal function in the superior and inferior tibiofibular articulations may assist in reducing nociceptive input from a fibular nerve that has become mechanically sensitive after an inversion ankle injury. 

Given the mechanical continuity of the nervous system, the clinician may need to examine nonneural structures along the entire neural tissue tract exhibiting increased mechanosensitivity (Butler, 2000). Intervention techniques may take the form of joint mobilization, soft-tissue work, taping to unload sensitive neural structures, or retraining neuromuscular control. An example of the latter was presented in a case report by Klingman (1999) addressing a patient with lumbar-leg symptoms during running and signs of neural tissue mechanosensitivity. Management incorporated calf stretching and weightbearing exercises for the gluteus

medius to reduce overpronation and improve frontal plane control of the pelvis. These interventions could facilitate relative unloading of mechanically sensitive lower extremity neural tissues associated with the tibial branch of the sciatic tract.

Addressing nonneural tissue impairments can often be a starting point for management when clinicians are less familiar with neural tissue mobilization, and the effect these techniques have on findings of neural tissue mechanosensitivity should be monitored closely (Butler, 1991, 2000).

Smaller scale clinical studies have shown that manual therapy techniques biased toward articular structures are more effective than no treatment for reducing pain and the need for surgery in patients with carpal tunnel syndrome (nZ21) (Tal-Akabi & Rushton, 2000) and for reducing pain and self-reported disability in patients with neck-arm pain of neurogenic origin (nZ30) (Allison, Nagy, & Hall, 2002). Lack of adequate improvement in response to non neural tissue management indicates the need to progress toward direct neural tissue mobilization techniques.

4.3. Neural tissue mobilization

Neural tissue mobilization techniques are passive or active movements that focus on restoring the ability of the nervous system to tolerate the normal compressive, friction, and tensile forces associated with daily and sport activities. It is hypothesized that these therapeutic movements can have a positive impact on symptoms by improving intraneural circulation, axoplasmic flow, neural connective tissue viscoelasticity, and by reducing sensitivity of AIGS (Butler,

2000; Shacklock, 2005), but these biologically plausible contentions have not been validated. 

These techniques may also be able to reduce unwanted fear of movement when provided in conjunction with appropriate neurobiology education, and therefore, they may reduce the reactivity of the pain neuromatrix (Butler, 2000; Moseley, 2003a). 

Clinical studies exploring neural tissue mobilization techniques that are cited in the following sections have commonly utilized changes in patients’ self-reports of pain, disability, or physical signs of mechanosensitivity as outcomes to detect an effect on the peripheral neuropathic pain state. 

4.4. Gliding techniques

Gliding techniques, or ‘sliders’, are neurodynamic maneuvers that attempt to produce a sliding movement between neural structures and adjacent nonneural tissues, and they are executed in a non-provocative fashion (Butler, 2000; Shacklock, 2005). A cervical lateral glide technique (Elvey, 1986; Vicenzino, Neal, Collins, & Wright, 1999) (Fig. 2) has been shown to produce immediate reductions in pain and signs of neural tissue mechanosensitivity in patients with lateral epicondylalgia (Vicenzino, Collins, & Wright, 1996) or neurogenic neck-arm pain (Coppieters, Stappaerts, Wouters, & Janssens, 2003a,b). Allison et al.

(2002) incorporated cervical lateral glide and shoulder girdle oscillation techniques (Elvey, 1986) in their randomized controlled trial on the treatment of patients with neurogenic neck-arm pain. 

The program utilizing these neural gliding techniques was more effective than no intervention for reducing pain and self-reported disability, and it was more effective than a program incorporating manual therapy techniques directed at the articular structures of the shoulder and thoracic spine in reducing pain at the completion of treatment. A non-randomized clinical trial demonstrated that adding nerve and tendon gliding techniques to conservative management reduced the Fig. 2. Cervical lateral glide technique. The head and cervical spine are translated in an oscillatory fashion away from the affected upper extremity that can be placed in a neurodynamically unloaded (top) or loaded (bottom) position depending upon the desired vigor of treatment (Elvey, 1986).

Fig. 3.

need for carpal tunnel surgery by nearly 30% (Rozmaryn et al., 1998), but a more recent randomized clinical trial found

that supplementing a program of splinting with nerve and tendon gliding exercises did not provide any additional improvements in severity of symptoms or function in patients with carpal tunnel syndrome (Akalin et al., 2002). Examples of neurodynamic ‘sliders’ are illustrated in Figs. 3 and 4 and have been well described by Butler (2005) and Shacklock (2005).

4.5. Tensile loading techniques 

As the name implies, the purpose of neurodynamic tensile loading techniques is to restore the physical capabilities of neural tissues to tolerate movements that lengthen the corresponding nerve bed. It is important to emphasize that tensile loading techniques are not stretches; these neurodynamic maneuvers are performed in an oscillatory fashion so as to gently engage resistance to

movement that is usually associated with protective muscle activity (Butler, 2000; Shacklock, 2005). The vigor of technique may be adjusted to elicit gentle stretching sensations or to evoke mild symptoms in rhythm with each oscillation (Butler, 2000). 

Tensile loading techniques  are more aggressive than neurodynamic ‘sliders’ (Butler, 2000; Shacklock, 2005), and they are not indicated in patients with clinical evidence of impairments in impulse conduction. Tal-Akabi and Rushton (2000) utilized neural tissue mobilization techniques in their randomized clinical trial on patients with carpal tunnel syndrome, but they did not

specify whether ‘sliders’ or tensile loading techniques were Fig. 4.

used. Neural tissue mobilization was more effective than no treatment for reducing pain and the need for carpal tunnel surgery, but neurodynamic techniques were no more effective than joint mobilization techniques that facilitated horizontal extension of the carpal bones. A clinical trial on Australian Rules football players with grade 1 hamstring strains and positive findings during the slump test demonstrated that supplementing a conservative management program with neurodynamic tensile loading techniques

led to a faster return to competition (Kornberg & Lew, 1989). 

Tensile loading techniques, with or without ‘sliders’, have also been used successfully in case studies or single-subject design studies describing patients with signs of increased neural tissue mechanosensitivity in combination with lumbar-lower extremity symptoms (Cleland, Hunt, & Palmer, 2004; George, 2002; Klingman, 1999), heel pain (Meyer et al., 2002; Shacklock, 1995a), lateral epicondylalgia (Ekstrom & Holden, 2002), and cubital tunnel syndrome (Coppieters, Bartholomeeusen, & Stappaerts, 2004). In contrast, a randomized controlled trial clearly demonstrated that neural tissue mobilization did not provide any additional benefit to standard postoperative care in patients who had undergone lumbar discectomy, laminectomy, or fusion (Scrimshaw & Maher, 2001). Examples of neurodynamic tensile loading techniques are presented in Figs. 5 and 6 and have been described in detail by Butler (2005) and Shacklock (2005).

4.6. Combined techniques

While nonneural and neurodynamic intervention techniques have been described separately, they may need to be combined in patients with less reactive peripheral neuropathic symptoms of musculoskeletal origin. An example of a combined intervention technique was presented in the previously mentioned case study by Klingman (1999) describing a patient with lumbar-leg pain during running with signs of neural tissue mechanosensitivity. The patient was placed in prone with the symptomatic limb off the side

of the table in a partial straight leg raise position, and unilateral posterior-anterior pressures were applied to the hypomobile motion segments in the lumbar spine. The choice and progression of any of these intervention techniques will be based on the results of reassessment of all of the components of the patient’s presentation of musculoskeletal peripheral neuropathic pain (Butler, 2000).

5. Conclusions

The positive and negative symptoms associated with musculoskeletal presentations of peripheral neuropathic pain are produced by sensitized nociceptors in neural connective tissues, hypersensitive AIGS, a sensitized pain neuromatrix, myelin changes, and axonal degeneration. It is proposed that conservative management incorporating neurodynamic and neurobiology education, nonneural

tissue interventions, and neurodynamic mobilization techniques can be effective in addressing musculoskeletal peripheral neuropathic pain states. While a small amount of clinical evidence lends some support to this proposal, much more clinical research is necessary to identify those patients with peripheral neuropathic pain that will respond most favorably to neurodynamic mobilization techniques and clarify specific treatment parameters that will be most effective. Regardless of the results of this future research,

conservative care will always need to be grounded in sound clinical reasoning so that interventions can be individualized to address the nuances of each patient’s presentation of musculoskeletal peripheral neuropathic pain.

neurodynamic, nervous system mobilization 1995년.pdf

Summary

Mobilisation of the nervous system is an approach to physical treatment of pain. The method relies on influencing pain

physiology via mechanical treatment of neural tissues and the non-neural structures surrounding the nervous system. Previous descriptions of this method have not clarified the relevant mechanics and physiology, including interactions between these two components. 

To address this, a concept of neurodynamics is described. The body presents the nervous system with a mechanical interface via the musculoskeletal system. With movement, the musculoskeletal system exerts non-uniform stresses and movement in neural tissues, depending on the local anatomical and mechanical characteristics and the pattern of body movement. This activates an array of mechanical and physiological responses in neural tissues. These responses include neural sliding, pressurisation, elongation, tension and changes in intraneural microcirculation. axonal transport and impulse traffic.

Because many events occur with body movement, in addition to tension, the term ’neural tension’ is incomplete and requires expansion to include both mechanical and physiological mechanisms. ‘Neural tension tests’ may be better described as ‘neurodynarnic tests’. Pathomechanics and pathophysiology in neural tissues and their neighbouring structures may be regarded as pathodynamics.