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Brachialgia Definition Radicular pain is a form of pain caused by irritation of the sensory root or the dorsal root ganglion (DRG) of a spinal nerve

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Radial Arm Maze

Definition

A behavioral test used to measure spatial and working memory.

 Nociceptive Processing in the Cingulate Cortex, Be- havioral Studies in Animals

Radiant Heat

Definition

In the Tail-Flick Test the nociceptive stimulus is often a light beam focused on the tip of the tail.

 Tail-Flick Test

Radiant Heat Test

 Thermal Nociception Test

Radiant Stimulation

 Pain in Humans, Thermal Stimulation (Skin, Muscle, Viscera), Laser, Peltier, Cold (Cold Pressure), Radi- ant, Contact

Radiculalgia

 Radicular Pain, Diagnosis

Radicular Leg Pain

 Sciatica

Radicular Nerve Root Pain

Definition

Pain radiating from the back (usually from a slipped disk) to a distal part of the leg (or arm).

Cancer Pain Management, Anesthesiologic Interven- tions, Neural Blockade

Radicular Pain

Definition

Pain in a dynatomal distribution (the distribution of referred symptoms caused by spinal nerve root irrita- tion), which may resemble the distribution of classic dermatomal maps for cervical nerve roots, but is not infrequently provoked outside of the distribution of these classic dermatomal maps.

Cervical Transforaminal Injection of Steroids

Radicular Pain, Diagnosis

Radicular Pain, Diagnosis

JAYANTILALGOVIND

Department of Anaesthesia, Pain Clinic, University of New South Wales, Liverpool Hospital, Sydney, NSW, Australia

jaygovind@bigpond.com

Synonyms

Radiculalgia; sciatica; Brachialgia

Definition

Radicular pain is a form of pain caused by irritation of the sensory root or the dorsal root ganglion (DRG) of a spinal nerve.

Radicular pain is not nociceptive pain, for the neural ac- tivity arises from the dorsal root, and not from stimu- lation of peripheral nerve endings. Therefore, it is not synonymous withsomatic painor somatic referred pain, and needs to be distinguished from them.

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2082 Radicular Pain, Diagnosis

Nor is radicular pain synonymous with radiculopathy.

Whereas radicular pain is caused by the generation of ectopic impulses, radiculopathy is caused by the block- ing of conduction along sensory and motor axons, and is characterised by loss of nerve function (Merskey and Bogduk 1994).

Characteristics

Pathophysiology

The introduction of computerised tomography (CT) and

magnetic resonance imaging(MRI) has brought into question the belief that a simple mass effect adequately accounts for the mechanism of lumbar radicular pain.

Studies have shown that in patients whose symptoms of sciatica had resolved, still showed the same mass effect on serial CTs, whilst conversely, disc herniations evi- dent on CT or MRI may not be associated with either low back or lumbar radicular pain (Bogduk and Govind 1999). In animal studies, compression of a normal nerve root causes only a momentary discharge, too brief to ac- count for radicular pain (Howe et al. 1977).

Ectopic impulses evoked by the compression of an unin- jured DRG produce a train of sustained discharges me- diated via the A–δ, C and the A–β fibres (Howe et al.

1977), which may account for the distinctive quality of radicular pain – its shooting or electric nature. Hence a mechanical basis for radicular pain can be accommo- dated, provided that the dorsal root ganglion is regarded as the source of pain.

However, experiments in laboratory animals (Howe et al. 1977) and in post-surgical patients (Smith and Wright 1959; Kuslich et al. 1991) have shown that radicular pain can be generated from nerve roots, provided that they have been previously damaged. Thus, for lumbar radic- ular pain, it is feasible that two distinctive but not mu- tually exclusive mechanisms prevail.

On the one hand, nerve roots that are chronically com- pressed may become sensitised to mechanical stimu- lation. Whilst the exact mechanism is not known, the pathogenesis might include partial damage to the axon, neuroma-in-continuity, or focal demyelination, intra- neural oedema, and impaired microcirculation, each of which is capable of generating ectopic impulses from the affected nerve (Devor 1996).

The second explanation invokes a chemically mediated non-cellular inflammatory process – a type of “chemical radiculitis”. Studies have shown the nucleus pulposus to be inflammatogenic and leukotactic (Olmarker et al.

1995); that injecting phospholipase A2(PLA2) into rat sciatic nerve produces demyelination, axonal injuries and increased macrophage phagocytic activity, and that the resulting mechanical hyperalgesia correlates with PLA2 immunoreactivity (Kawakami et al. 1996). In the absence of nerve compression, applying nucleus pulposus in the epidural space causes a delay in the nerve conduction velocity of nerve roots, and methyl

prednisolone injected intravenously within twenty hours, prevents this reduction in conduction velocity (Olmarker et al. 1994).

The evidence would suggest that, unlike the DRG, for the dorsal nerve root to be a source of radicular pain due to disc herniation, an injury either mechanically or chem- ically induced is a pre-requisite.

With respect to cervical radicular pain, there are no equivalent experimental data. One study showed that applying a sufficiently strong stimulus to a normal dorsal nerve root is always followed by a peripheral radiation of pain; but gentle stimulation of dorsal roots previously affected by compressive lesions, evoked a sensation of pain or paraesthesia (Fryckholm 1951).

Herniated cervical intervertebral discs have been shown to produce nitric oxide, metalloproteinases, interleukin- 6 and prostaglandin E2(Kang et al. 1995), but their role as possible mediators of nerve root inflammation has not been fully ascertained.

Clinical Features

Radicular pain has certain distinctive qualitative fea- tures. It is not dull or achy in quality. Where radicular pain has been produced experimentally, in all instances it has been perceived as a shooting or lancinating pain (Smith and Wright 1959; Kuslich et al. 1991) and unlike somatic pain, radicular pain has both a cutaneous and deep quality. Radicular pain can be episodic, recurrent or paroxysmal.

In the case of lumbar and sacral radicular pain, the pain is felt in the lower limb when L4, L5, S1, or S2 nerve roots are involved. Pain is typically felt along the back of the thigh, into the leg and into the foot. Pain does not follow the corresponding dermatome. Lumbar radicular pain travels through the lower limb along a narrow band usually not more than 5–8 cm wide (Smith and Wright 1959). Whilst it may be felt throughout the entire length of the lower limb, it is more commonly experienced be- low the knee than above the knee.

With respect to the cervical spine, typical patterns of radicular pain have been mapped (Slipman et al. 1998), but cervical radicular pain and cervical somatic referred pain have similar distributions. Hence the pattern of pain cannot be used to determine its cause or mecha- nism. Pain over the shoulder girdle and upper arm can be either somatic referred pain or radicular pain, but pain in the forearm and hand is unlikely to be somatic referred pain, and is more likely to be radicular in na- ture (Bogduk 1999). Pain that radiates into the upper limb, and is shooting electric in quality, is bound to be radicular in origin.

Aetiology

A large number of lesions have been reported to cause radicular pain (Bogduk and Govind 1999; Bogduk 1999). Systematically, any abnormality of the vertebral column, or any space-occupying lesion of spinal tissues,

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Radiculopathies 2083

that impinges on a spinal nerve or its roots may cause radicular pain. These include: osteophytes, cysts, and tumours of the vertebral column; cysts and tumours of the spinal cord, nerve roots, and their dural sheaths;

tumours of epidural fat and blood vessels; and infec- tions, infestations, or metastatic deposits in the vertebral column or vertebral canal. However, herniation of an intervertebral disc is the single most common cause, followed by foraminal stenosis due to osteoarthrosis of the zygapophysial joints.

The differential diagnosis includes intrinsic disorders of the dorsal root or its axons, such as diabetic neuropathy, postherpetic neuralgia, and various, rare dorsal root gan- glionopathies.

Diagnosis

Radicular pain must be distinguished from somatic referred pain. Although not an absolute distinction, radicular pain is sharp, shooting or lancinating in qual- ity, and topographically it must involve a region beyond the spine. Imaging studies, including computerised tomography and magnetic resonance imaging, may assist in determining both the putative cause and the segmental level. Features of radiculopathy including absent reflexes, weakness, numbness or muscle wasting may be evident clinically. Electrophysiological tests for the investigation of patients with acute radicular pain are generally not helpful (Bogduk and Govind 1999;

Bogduk 1999).

Treatment

Physicians often prescribe what is commonly referred to as “conservative therapy” for radicular pain. Typically, this consists of exercises, traction, analgesics, and other measures, such as collars for cervical radicular pain.

Multiple studies have shown that these interventions confer no benefit greater than that of the natural history of the condition (Bogduk and Govind 1999; Bogduk 1999).

Traditionally, the mainstay for treatment of radicular pain has been surgery, in the form of laminectomy and microdiscectomy for lumbar radicular pain, and foraminotomy for cervical radicular pain. Studies have shown that surgery does not achieve better long-term outcomes than conservative therapy, but surgery has the distinct advantage of providing prompt relief when used for patients with severe pain that does not respond to other measures (Bogduk and Govind 1999; Bogduk 1999).

Other interventions that have been advocated and tested for radicular pain include epidural injection of steroids, andTransforaminal Injection of Steroids.

References

1. Bogduk N (1999) Medical Management of Acute Cervical Radic- ular Pain: An Evidence-Based Approach. Newcastle Bone and Joint Institute, Newcastle

2. Bogduk N, Govind J (1999) Medical Management of Acute Lum- bar Radicular Pain: An Evidence-Based Approach. Newcastle Bone and Joint Institute, Newcastle

3. Devor M (1996) Pain Arising from Nerve Root and Dorsal Root Ganglion. In: Weinstein JN, Gordon SL (eds) Low Back Pain:

A Scientific and Clinical Overview. American Academy of Or- thopaedic Surgeons Rosemont, Illinois, pp 187–208

4. Fryckholm R (1951) Cervical Nerve Root Compression Result- ing from Disc Degeneration and Root-Sleeve Fibrosis: A Clinical Investigation. Acta Chirurgica Scandinav Supp 160:10149 5. Howe JF, Loeser JD, Calvin WH (1977) Mechanosensitivity of

Dorsal Root Ganglia and Chronically Injured Axons: A Physio- logical Basis for the Radicular Pain of Nerve Root Compression.

Pain 3:25–41

6. Kang JD, Georgescu HI, McIntyre-Larkin L, Stanovic-Racic M, Evans CH (1995) Herniated Cervical Intervertebral Discs Spon- taneously Produce Matrix Metalloproteinases, Nitric Oxide, Interleukin-6 and Prostaglandin E2. Spine 22:2373–2378 7. Kawakami M, Tamaki T, Weinstein JN, Hashizume H, Nishi I,

Meller ST (1996) Pathomechanism of Pain-Related Behaviour Produced by Allografts of the Intervertebral Disc in the Rat.

Spine 21:2101–2107

8. Kuslich SD, Ulstrom CL, Michael CJ (1991) The Tissue Origin of Low Back Pain and Sciatica: A Report of Pain Response to Tissue Stimulation during Operations on the Lumbar Spine using Local Anaesthesia. Ortho Clinic North Amer 22:181–187 9. Merskey H, Bogduk N (eds) (1994) Classification of Chronic

Pain. Description of Chronic Pain Syndromes and Definitions of Pain Terms, 2ndedn. IASP Press, Seattle 1994

10. Olmarker K, Blomquist J, Stromberg J, Nanmark U, Thomsen P, Rydevik B (1995) Inflammatogenic Properties of Nucleus Pul- posus. Spine 20:665–669

11. Olmarker K, Byrod G, Cornefjord M, Nordberg B, Rydevik B (1994) Effects of Methyl Prednisolone on Nucleus Pulposus In- duced Nerve Root Injury. Spine 19:1803–1808

12. Slipman CW, Plastaras CT, Palmitier RA, Huston CW, Sterenfeld EB (1998) Symptom Provocation of Fluoroscopically Guided Cervical Nerve Root Stimulation: Are Dynatomal Maps Identical to Dermatomal Maps? Spine 23:2235–2242

13. Smith MJ, Wright V (1959) Sciatica and the Intervertebral Disc.

An Experimental Study. J Bone Joint Surg 40A:1401–1418

Radiculopathies

PAOLOMARCHETTINI

Pain Medicine Center, Scientific Institute San Raffaele, Milano, Italy

marchettini.paolo@hsr.it

Synonyms

Root disease; sciatica; lumbago; cauda equina; neck pain; back pain

Definition

Radiculopathyis a pathological condition affecting the spinal roots of peripheral nerves (seespinal root disease). The term has no implication for the mecha- nism causing damage to the root, which may be mechan- ical compression / ischemia, inflammation or primary or metastatic tumour. Spondyloarthritis is by far the most common cause of radiculopathy. Radiculopathy, inde- pendent of the cause, is, in the majority of cases, a painful

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2084 Radiculopathies

medical condition. Besides pain, root injury may also cause weakness and sensory disorder. Weakness is ob- vious in the limbs, while abnormal sensation may also be detected in the chest and abdomen. Patients with radicu- lopathy tend to seek the opinion of a specialist in or- thopaedic surgery, neurology or neurosurgery or, when pain prevails, of a pain specialist or an anaesthesiologist.

Characteristics

Clinical Features

Pain and related sensory motor symptoms in radicu- lopathy may appear suddenly (acute) or develop slowly with progressive increase, followed by improvement and relapse (chronic). Acute radiculopathy is almost exclusively caused by sudden compression of a root by a herniated intervertebral disk. In some cases the root is squeezed inside the radicular pocket by a disk frag- ment herniated into the foramina. The compressed root undergoes ischemia and also swelling that worsens the ischemia. Pain is usually reported to be very intense, interfering with common simple daily activities and sleep.

Pain is both nociceptive, originating from the ruptured ligament, the perineural sheath and the meninges, and neuropathic, originating from ectopic impulses gen- erated by mechanical compression and ischemia of nociceptive afferents (small myelinated and myeli- nated). The nociceptive pain originates at root level and spreads above or below along the spine. The neu- ropathic pain radiates into the innervation territory of the root. Quite often nociceptive pain in lumbosacral radiculopathy is worsened by manoeuvres that increase spinal fluid pressure, such as sneezing, coughing and voiding. Such manoeuvres more rarely increase neck and upper limb pain in cervical radiculopathy. Transient mechanical compression of the cord causes sensations of an “electric shower” known as the Lehrmitte sign.

Lehrmitte’s sign, which is usually not painful, may be provoked by forced extension or flexion of the neck.

Lateral rotation of the head in the opposing direction of an elevated arm may cause root stretching in cervical radiculopathy (Spurling sign). Elevation of a lower limb in the supine position causes lumbosacral root stretching (Lasègue sign). Spurling and Lasègue signs are commonly painful, evoking both local pain (in the neck or back) and radicular pain. The single root stim- ulated by such manoeuvres may be readily identified by the selective anatomical distribution of the radicu- lar dysesthesias. Neuropathic sensory symptoms and neuropathic pain are projected into the root’s anatom- ical territory. This anatomical territory consists of the cutaneous and also the bone and muscle structures innervated by that root (territory of positive sensation).

It is a territory wider than the area of cutaneous hy- poesthesia that may ensue following complete root section (territory of negative sensation) (Marchettini

1993; Marchettini and Ochoa 1994). Many patients are good “witnesses” and clearly perceive and describe the difference between the pain originating from ligaments (purely nociceptive) and the pain originating from root compression (nociceptive and neuropathic).

The typical medical history of radiculopathy in disk her- niation is of preceding neck or back pain for many days or even months, which over time becomes very intense and more focal. The back pain suddenly disappears and is fol- lowed within hours by the radicular pain. Radicular pain combines nociceptive neck or back pain of various qual- ities, with neuropathic pain projected into the limb. The

neck pain, which is due to meningeal and cervical root compression, radiates over a wide area in the neck, and is often referred into the scapular area. The equivalent back pain radiates into the buttocks. The neuropathic radic- ular pain combines large fibre positive symptoms (tin- gling and numbness) and small fibre positive symptoms (pins and needles from small myelinated fibres, burning, deep soreness, squeezing and cramp-like from unmyeli- nated fibres). Axonal degeneration is not confined to the site of root compression, but extends to the primary sen- sory neurons within the dorsal root ganglion as a result of the axon reaction. Therefore sensory loss may be long lasting even after root decompression.

When the disk pinches the root, any movement elongat- ing it worsens the pain. This leads to reflex paraspinal muscle contraction to avoid movement and to the search for a comfortable position reducing radicular stretching.

This position is usually neck and back hyperextension and limb flexion, particularly the lower limb. To further avoid radicular stretching, patients tend to sleep on their side. In the cauda equinasyndrome, short distance walking evokes symptoms of neuropathic pain and paresthesias in the legs and buttocks. Curiously, biking or walking, or any lower limb activity practiced while bending forward, may be symptom-free. Probably this happens because tilting forward reduces intraspinal pressure and interferes less with radicular blood flow.

Rare alternative mechanical causes of single segment radiculopathy or cauda equina syndrome are epidural varices (Genevay et al. 2002), synovial cysts (Yarde et al. 1994) or even perineural cysts filled with cere- brospinal fluid (Tarlov 1938). Primary root tumours are Schwannomas and neurinomas. Spinal roots may also be compressed by bone metastasis or, more rarely, invaded by leptomeningeal metastasis. The latter event is becoming more common because of spinal fluid sequestration of metastatic cells in patients surviving systemic chemotherapy.

History

Until the mid part of the last century, intervertebral disc herniation, which is the most common cause of radiculopathy, was hard to distinguish among the mul- tiple other nerve root diseases caused by tuberculosis, syphilis and cancer. Radiculopathy caused by disk com-

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Radiculopathies 2085

pression was often recognised late when it reached the paralysing state and thus carried a poor general progno- sis. Nevertheless, in the late 1940’s Guillain and Barré polyradiculoneuropathy, which is a rare condition, was considered the most common “reversible” or “curable”

root disease (Henri Roger quoted by Bénard 1966).

Historical note, Cotugno, a master of the Salernitan School, is classically credited with having been the first to describe the characteristic distribution of radicular pain in the leg that in 1764 he named “sciatica” (is- chias postica, or morbus ischiaticus). However it is not until 1934 that Mixter and Barr (quoted by Parisien and Ball 1998) established a relationship between rupture of the intervertebral disc and lumbosacral radiculopathy, an observation that took about two additional decades to gain wider recognition. This knowledge led to enthu- siastic, aggressive root decompression through surgical laminectomy that consequently produced a new ia- trogenic entity, the “failed back surgery syndrome”.

The second most common cause of radiculopathy in spondyloarthritis, the intermittent claudication of the cauda equina, was recognised later by Blau and Logue in 1961.

Anatomy

Nerve roots are made of 4–5 voluminous fascicles that ramify distally and give rise to the peripheral nerve plexus and peripheral nerves. Radicular fascicles al- ready posses anatomical segregation, each one hosting fibres of well defined peripheral territories. Thus, partial root compression affecting one or two fascicles may mimic a peripheral nerve injury. Radicular fascicles are separated by epineural septa and embedded in the connective tissue of the perineurium. From the radicular pocket inward into the spinal canal, the perineurium fuses with the dura mater and is surrounded by the arach- noid that keeps the nerve root bathed in cerebrospinal fluid. Meninges and perineurium are sensitive struc- tures, innervated by nociceptive nerve endings. As a consequence, inflammation and trauma of nerve roots always causes pain of mixed quality with irritation of the meninges and perineurium (nociceptive pain) and of radicular axons (neuropathic pain). Cervical and thoracic roots cross the intervertebral foramen corre- sponding to their anatomical level, while the lumbar and sacral roots show a progressive downward shift, due to the termination of the conus medullaris approximately at the first lumbar vertebral body. As a consequence, the cauda equina’s lumbar and sacral roots first travel downwards within the vertebral canal and then reach the intervertebral foramen by taking off sideways with a variable angle (mean 40˚ for the lumbar and 23˚ for the sacral roots). Because of this they are more exposed to ischemia than thoracic or cervical roots. At the L4–L5 intervertebral level the L5 root is situated anterolater- ally, displacing the S1 root laterally, while the lower sacral roots are positioned dorsally. Therefore the most

common disk protrusion, the L4–L5, may hit the L5 or S1 root depending on the median or lateral side of its bulging or herniation. Nerve roots receive a vascular supply from peripheral and central sources. However they are not served by a regional segmental supply. In the case of the cauda equina, ischemia is a considerable risk because the majority of the arteries are “end” ar- teries without effective anastomotic connections. The neural structure of the cauda equina occupies about half (44 %) of the cross sectional area of the spinal space. Constriction of the spinal canal increases the spinal fluid pressure on the roots by about 50 mm Hg for each 3rdreduction from normal. As a consequence, narrowing of the spinal canal severely affects the blood supply to the cauda equina.

Diagnostic Work-up

Plain radiographs have been the traditional first-choice imaging technique and many clinicians still routinely prescribe them in back pain patients. It is well recog- nised, however, that particularly in the early stages of disc disease or other vertebral diseases, they have a low yield (McNally et al. 2001). Plain radiographs may show indirect signs of disc degeneration through reduction of the intervertebral space and osteoarthritic changes.

However, such signs appear only in the advanced stages of spondyloarthritis. Their main utility is to rule out more worrisome causes of back pain and radiculopathy such as infection or metastasis. A loss of about 80 % of vertebral bone may be required before a destructive lesion can be visualised with this method. In addition plain radiographs cannot define the cause of nerve root compression. CT scanning allows proper examination of horizontal planes and explores roots and disks that are best visualised when degenerative changes from gas formation and calcification begin to appear. The gas, also known as vacuum phenomenon, was first observed by Fick in 1910; in 1942 Knutsson described its radio- graphic characteristics and it was first analysed by Ford and co-workers (1977), who reported that the gas was 90-95% nitrogen. CT scans, however, may completely miss early disk pathology. MRI, eventually with limited timesaving protocols, is becoming the method of first choice to explore radiculopathy.

One has to be aware that imaging techniques cannot pre- dict clinical outcome. In the case of CT scans, for exam- ple, it has been shown that none of the features of disk herniation has any significant correlation with the pain prognosis. On the contrary, larger herniation or the pres- ence of free disk fragments may be more common in pa- tients who go on to have good outcomes (Beauvais et al.

2003). The same probably applies to MRI.

Another prognostic approach, electromyography, does not reveal all structural or clinical radiculopathy. How- ever, its sensitivity may reach 92 % (Dillingham and Dasher 2000). In lumbosacral radiculopathy, elec- tromyographic screening of 4 to 5 leg and paraspinal

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2086 Radiofrequency

muscles may provide valuable information in 89 % of cases of root disease. Electromyography is indi- cated when differential diagnosis is considered. The most common examples are polyradiculoneuropathy (Guillain-Barré), plexopathy, multineuropathy and the overall assessment of the patient to examine peripheral nerve function when systemic diseases such as severe diabetes or uraemia coexist. Electromyography is also recommended as a pre-surgical assessment before per- forming laminectomy, particularly in the presence of muscle weakness.

Therapy

The majority of patients heal spontaneously without needing invasive procedures. Pain control is the only medical need in most cases. However, the clinical course in radiculopathy is quite variable. Although symptoms usually improve within 2 weeks, in a conspicuous mi- nority of patients pain continues for months and at times years. In the first 2 months about 60 % of the patients have a marked improvement in back and leg pain. By 1 year, one third are still complaining of back or leg pain.

Surgery is usually decided upon within the first year.

Large and migrated disk herniations decrease sponta- neously more than disk protrusions or small-contained herniations. Morphologic changes (reduction in protru- sion or even hernia re-entry) may be observed; however they usually follow rather than anticipate the clinical improvement.

In addition, clinical improvement may be quite remark- able in the absence of morphological improvement. New minimally invasive percutaneous techniques have been proposed to reduce the risk of chronic arachnoiditis fol- lowing back surgery. However, there are no clinical trials of percutaneous discectomy technique to provide defi- nite evidence supporting the efficacy oradvantages of the procedure. The success rate is 41 % for percutaneous dis- cectomyversus 40 % for the conventional open method (Haines et al. 2002). There is controversy regarding the use of epidural steroids. The only agreement regarding its efficacy is in decreasing the symptoms of the acute phase (Boswell et al. 2005). There is no clear evidence that epidural steroids alter the natural history of radicu- lopathy or the morphology of herniation.

Cervical Transforaminal Injection of Steroids

Pain Treatment, Spinal Cord Stimulation

Whiplash

References

1. Beauvais C, Wybier M, Chazerain P et al. (2003) Prognostic value of early computed tomography in radiculopathy due to lumbar intervertebral disk herniation. A prospective study. Joint Bone Spine 70:134–139

2. Bénard H (1966) Eulogy of Henri Roger (1860-1946) Bull Acad Natl Med 150: 651–656

3. Blau JN, Logue V (1961) Intermittent claudication of the cauda equina: an unusual syndrome resulting from central protrusion of a lumbar intervertebral disc. Lancet 277:1081–1086

4. Boswell MV, Shah RV, Everett CR et al. (2005) Interventional techniques in the management of chronic spinal pan: Evidence- based practice guidelines. Pain Physician 8:1–47

5. Dillingham TR, Dasher KJ (2002) The lumbosacral electromyo- graphic screen: Revisiting a classic paper. Clin Neurophysiol 111:2219–2222

6. Fick R (1910) Handbuch der Anatomie und Mechanik der Ge- lenke unter Berücksichtigung der bewegenden Muskeln, vol 2.

G Fischer, Jena

7. Ford LT, Gilula LA, Murphy WA, Gado M (1977) Analysis of gas in vacuum lumbar disc. Am J Roentgenol 128:1056–1057 8. Genevay S, Palazzo E, Huten D et al. (2002) Lumboradiculopathy due to epidural varices: Two case reports and a review of the literature. Joint Bone Spine 69:214–217

9. Haines SJ, Jordan N, Boen JR et al. (2002) Discectomy strategies for lumbar disc herniation: Results of the LAPDOG trial. J Clin Neurosci 9:411–417

10. Knutsson F (1942) The vacuum phenomenon in the intervertebral discs. Acta Radiol 23:173–9

11. Marchettini P (1993) Muscle pain: animal and human experi- mental and clinical studies. Muscle Nerve 16:1033–1039 12. Marchettini P, Ochoa JL (1994) The clinical implications of re-

ferred muscle pain sensation. Am Pain Soc J 3:10–12 13. McNally EG, Wilson DJ, Ostlere SJ (2001) Limited magnetic

resonance imaging in low back pain instead of plain radiographs:

experience with first 1000 cases. Clin Radiol 56:922–925 14. Orendacova J, Cizkova D, Kafka J et al. (2001) Cauda equina

syndrome. Prog Neurobiol 64:613–637

15. Parisien RC, Ball PA (1998) William Jason Mixter (1880-1958).

Ushering in the “dynasty of the disc” Spine 23:2363–2366 16. Tarlov IM (1938) Perineural cysts of the spinal root. Arch Neurol

Psych 40:1067–1074

17. Yarde WL, Arnold PM, Kepes JJ et al. (1995) Synovial cysts of the lumbar spine: Diagnosis, surgical management, and pathogenesis report of eight cases. Surg Neurol 43:459–465

Radiofrequency

Definition

An electric current oscillating at high frequencies, usu- ally > 400,000 cycles per second.

Facet Joint Pain

Radiofrequency Ablation

Definition

The use of heat delivered via a high-frequency current to destroy tissue.

Cancer Pain Management, Neurosurgical Interven- tions

Facet Joint Procedures for Chronic Back Pain

Radiofrequency Denervation

Definition

Procedure by which a nerve is coagulated by heating the tip of an electrode to 80˚C, with consequent loss of no- ciceptive transmission.

Whiplash

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Radiofrequency Neurotomy, Electrophysiological Principles 2087

Radiofrequency Lesion

 Radiofrequency Neurotomy, Electrophysiological Principles

Radiofrequency Neurotomy, Electrophysiological Principles

JAYANTILALGOVIND

Department of Anaesthesia, Pain Clinic, Liverpool Hospital, University of New South Wales, Sydney, NSW, Australia

jaygovind@bigpond.com

Synonyms

RF; Thermo-coagulation; Radiofrequency Lesion; Heat Lesion; Thermal Neuroablation

Definition

Radiofrequency (RF) neurotomy is a means of treat- ing pain, by which the nerves from a source of pain are coagulated using an electrode, through which a high-frequency electrical current is passed, in order to heat the tissues immediately surrounding the tip of the electrode.

Characteristics

RF neurotomy is not electrocautery. It is the creation of a targeted, therapeutic, thermal lesion achieved by passing a low energy, high frequency, alternating cur- rent (100,000 – 500,000 Hz) between the small surface area on the uninsulated tip of an (active) electrode, and the large surface area of a ground plate (the dispersive electrode) that is applied to a remote area of the body.

The concentration of current in tissues around the active electrode achieves sufficient density to denature those tissues by heating them.

In Pain Medicine, RF neurotomy is used to coagulate peripheral nerves, in order to block nociceptive infor- mation from a source that is responsible for a patient’s pain. Similar techniques are used to produce lesions in the central nervous system for the relief ofcentral pain.

Electrophysiological Principles

Figure 1 illustrates the pattern of the electric current lines in the body between the active and dispersive electrode.

The current leaving the large area of the dispersive plate is concentrated onto the small area of the exposed tip of the electrode.

The alternating current produced by the generator passes through the body, and agitates charged molecules in the tissues, thereby heating them. Where the current con- verges and concentrates towards the active tip of the elec- trode, current density is greater and heating is greater.

Heating occurs as a result of agitation of charged molecules in the tissues and the resultant friction be- tween them. Thus, the tissue adjacent to the electrode becomes the source of heat, not the electrode itself.

In proportion to the current density, temperatures are higher closer to the electrode. Accordingly, around the tip of the electrode, isotherms can be depicted (Fig. 2).

If tissues are heated sufficiently they coagulate. The vol- ume of coagulated tissue assumes the shape of a “pro- late spheroid” (Organ 1976), whose long axis is formed along the uninsulated tip of the electrode (Fig. 3)

Creation and Size of Lesion

The principal factors that govern temperature equi- librium between the electrode and the heated tissue are distance from the tip (r), current intensity (I), and duration (t) of application (Lord and Bogduk 2002).

Tissue heating (T) varies with the square of the current intensity (I2); it decreases rapidly away from the tip by a factor of 1 / r4; and increases with the duration of ap- plication. Mathematically the relationship is (Lordand Bogduk 2002):

where K is a constant.

Sufficient time must be allowed for some of the heat to be transmitted to the periphery of the lesion volume. Opti- mal current should generate a lesion of a maximum vol- ume for the size of the electrode tip. The rapid application of high current, however, may result in solidification and char formation, which in turn will impede current flow and heating. Due to the increased resistance, lesion-size becomes submaximal.

As the temperature of the electrode reaches 60˚C, coag- ulation commences on the surface of the electrode tip (Lord and Bogduk 2002, Lord et al. 1988, Bogduk et al. 1987). The volume of coagulated tissue expands as the temperature reaches 80˚C. At this temperature, the lesion is initially about 60% of maximal achievable size.

If temperature is maintained at 80˚C for thirty seconds, the lesion increases to 85% size. After sixty seconds, it reaches 94% maximal size. The growth of the lesion asymptotes at 90 seconds. Maintaining the current for longer than this does not achieve appreciable increases in the size of the lesion (Bogduk et al. 1987). Accord- ingly, the optimal duration for the maximal coagulation lies between sixty and ninety seconds.

Temperature monitoring is critical to safety. During co- agulation the temperature should be increased slowly from body temperature to 80˚C. A rate of 1˚C per second is recommended. This slow increase allows patients to report any untoward sensations, and allows the opera- tor to abort the lesion before any appreciable damage is done. Maintaining the temperature under 85˚C not only

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2088 Radiofrequency Neurotomy, Electrophysiological Principles

Radiofrequency Neurotomy, Electrophysiological Principles, Figure 1 The electric field produced by a radiofrequency (RF) generator, between a ground plate on the body surface and an electrode introduced into the body. The field lines converge on the tip of the electrode.

Radiofrequency Neurotomy, Electrophysiological Principles, Figure 2 The isotherms of a radiofrequency current. As the electric field (E) oscillates, tissues are heated in proportion to the density of the field lines. Around the tip of the electrode, a temperature gradient is established, with temperatures highest at the surface of the electrode, but progressively less away from the electrode. The isotherms represent regions with the same temperature. The 65˚ isotherm is labelled.

ensures creating a lesion of maximal volume, but also avoids the risk of boiling, charring, and gas or steam for- mation, which can occur when higher temperatures are applied, and which compromise both the safety and the efficacy of the lesion made.

During coagulation, impedance should remain reason- ably constant as power and temperature are increased.

Erratic behaviour of the impedance and fluctuation of temperature indicates either faulty equipment or connec- tions, or dissipation of heat into tissues such as blood or other fluids.

Electrodes with larger exposed tips produce larger le- sions. Longer exposed tips produce elongated, elliptical lesions (Organ 1976; Alberts et al. 1966). Coagulation occurs principally in a radial direction perpendicular to the long axis of the electrode, i.e. sideways (Lord and Bogduk 2002; Lord et al. 1988; Bogduk et al. 1987).

Depending on the shape of the point of the electrode, relatively less coagulation occurs distal to the point.

The dimensions of lesions generated are proportional to the size of the electrode used, and can be nor- malised and expressed in terms of electrode-widths (Lord et al. 1988). In a radial direction, large di- ameter (1.6 mm) electrodes coagulate tissues up to 1.6 ± 0.3 (mean ± sd) electrode-widths away from the surface of the electrode. Distally, tissues up to 0.4± 0.2 electrode-widths from the tip of the electrode are coagulated. With electrodes of smaller diameter (0.7 mm), the radial range is 2.3± 0.4 electrode-widths, and the distal range is 1.4± 0.4 electrode-widths.

These figures indicate that electrodes must be placed ac- curately, i.e. very close to the target nerve, in order to en- sure that it is coagulated. Since the electrode-width of smaller electrodes is less than 1 mm, the electrode will,

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R

Radiofrequency Neurotomy, Electrophysiological Principles 2089

Radiofrequency Neurotomy, Electrophysiological Principles, Figure 3 The shape of a radiofrequency lesion. Tissues are heated in a more radial direction from the tip of the electrode than in a distal direction. On average, the effective radius (r) of the lesion is about twice the diameter, or less, of the electrode’s width (ew).

on average, coagulate nerves within 2 mm of its surface.

However, there is a 17.5% chance of failing to coagu- late the nerve, if it is not within 1.3 mm (mean size of lesion minus one sd) of the electrode. Larger electrodes coagulate tissues within 2.6 mm from their surface, with a one standard deviation lower limit of 2 mm.

Electrodes placed perpendicular to the target nerve may miss coagulating the nerve completely (Fig. 4a).

For optimal coagulation, the electrode must be placed parallel to the nerve (Lord and Bogduk 2002; Lord et al. 1988; Bogduk et al. 1987). Creating multiple, parallel lesions compensates for possible inaccuracies in placing the electrode exactly on the target nerve.

However, to be effective those lesions must be centred no further than one electrode-width from another. At greater displacements, nerves may escape coagulation because of the circular, cross-sectional shape of the lesions generated (Fig. 4b).

Physiology

By coagulating neural tissue, RF neurotomy creates a mechanical barrier to the transmission of nociceptive traffic. The denatured proteins in the nerve are incapable

Radiofrequency Neurotomy, Electrophysiological Principles, Figure 4 The problems of matching a radiofrequency electrode (e) and its lesion to the target nerve (n). (a) top view; (b) transverse view; of an electrode placed perpendicularly onto a nerve. Although the electrode rests on the nerve, the lesion it makes is largely proximal to the nerve, for little lesion is produced distal to its tip. As a result the nerve may escape complete coagulation. (c) top view; (d) transverse view; of electrodes placed parallel to the target nerve. Since the electrodes coagulate transversely, the nerve is more likely to be incorporated into the lesion.

(e) top view; (f) transverse view; of an electrode placed in two positions on a target nerve. If the two placements are not more than two electrode widths apart, their lesions overlap, and maximise the likelihood of the nerve being coagulated thoroughly.

of transmitting action potentials across the denatured zone.

Earlier views, that radiofrequency neurotomy selec- tively destroys Aδ and C fibres (Letcher and Goldring 1968), have not been corroborated. Experiments have established that radiofrequency neurotomy results in indiscriminate destruction of small unmyelinated, small myelinated and large myelinated fibres (Smith et al. 1981), including alpha motor neurones (Dreyfuss et al. 2000).

Recovery from RF neurotomy is not a simple matter of nerve regeneration. Before regeneration can occur, the coagulated proteins have to be removed and replaced,

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2090 Radiofrequency Rhizotomy

and the affected segment of nerve reconstituted. This takes considerably longer time than conventional regen- eration of a nerve after it has been cut.

Indications

The classical indication for RF neurotomy istrigeminal neuralgia. Otherwise, RF neurotomy can, in principle, be applied to any peripheral nerve that has been shown to be responsible for mediating a patient’s pain. However, the procedure has only been validated in the context of certain forms of spinal pain.

Pain arising from the lumbar or cervical zygapophysial joints can be treated by performing RF neurotomy of the nerves that innervate those joints. The cardinal indica- tion for this therapy is complete relief of pain following controlled,lumbar medial branch blocksorcervical medial branch blocks, respectively.

Experimental applications include lumbar discogenic pain and certain forms of sacroiliac joint pain (Lord and Bogduk 2002).

Side Effects and Complications

In principle, the side effects of RF neurotomy are due to the loss of function of the nerve that is coagulated. If the nerve has a cutaneous distribution, numbness will oc- cur in that distribution. Hyperaesthesia may complicate this denervation. If the nerve has a major proprioceptive function, impaired proprioception should be expected.

When motor fibres are coagulated, muscle denervation will occur.

The generic complications that may occur are those associated with any percutaneous procedure: infec- tion, haemotoma, allergy, and unintended damage to structures adjacent to the target nerve. Potential com- plications specific to RF neurotomy are electrical in nature, and include burns resulting from damaged insu- lation of the electrode, or from incorrect application of the dispersive plate. In particular, alternatives to plate electrodes, such as spinal needles, should not be used as the ground electrode. In that event, current concentrates around the needle and will cause burns along its entire length.

Efficacy

To be consistent with the rationale for the procedure, complete relief of pain should be the standard outcome.

If diagnostic blocks produce complete relief, so should RF. If complete relief is not achieved, either the patient was incorrectly selected or the procedure may have been technically imperfect.

Specific data, from observational studies and from controlled studies, are available forcervical medial branch neurotomy, for lumbar medial branch neu- rotomyand for trigeminal neurotomy. Early data are available for sacroiliac neurotomy. These are provided in the sections dealing with these procedures. For other

applications of RF neurotomy, comparable data are not available.

References

1. Alberts WW, Wright EW, Feinstein B, von Bonin G (1966) Ex- perimental Radiofrequency Brain Lesion Size as a Function of Physical Parameters. J Neurosurg 25:421–423

2. Bogduk N, MacIntosh J, Marsland A (1987) Technical Limita- tions to the Efficacy of Radiofrequency Neurotomy for Spinal Pain. Pain 20:529–535

3. Dreyfuss P, Halbrook B, Pauza K, Joshi A, McLarty J, Bogduk N (2000) Efficacy and Validity of Radiofrequency Neurotomy for Chronic Lumbar Zygapophyseal Joint Pain. Spine 25:1270–1277 4. Letcher FS, Goldring S (1968) The Effect of Radiofrequency Current and Heat on Peripheral Nerve Action Potential in the Cat. J Neurosurg Sci 29:42–47

5. Lord SM, Bogduk N (2002) Radiofrequency Procedures in Chronic Pain. Best Practice and Research. Clin Anaes- thetiol 16:597–617

6. Lord SM, McDonald GJ, Bogduk N (1988) Percutaneous Ra- diofrequency Neurotomy of the Cervical Medial Branches: A Validated Treatment for Cervical Zygapophyseal Joint Pain. Neu- rosurgery Quarterly 8:288–308

7. Organ LW (1976) Electrophysiologic Principles of Radiofre- quency Lesion Making. Appl Neurophysio 39:69–76 8. Smith HP, McWhorter JM, Challa VR (1981) Radiofrequency

Neurolysis in a Clinical Model: Neuropathological Correlation.

J Neurosurg 55:246–253

Radiofrequency Rhizotomy

Definition

Treatment of TN by an injury produced by a radiofre- quency current, applied through a needle placed in the space around the sensory (Gasserian) ganglion contain- ing the cell bodies of the sensory fibers in the trigeminal nerve.

Trigeminal, Glossopharyngeal, and Geniculate Neu- ralgias

Radiography

Plain Radiography

Radioisotope

Definition

An isotope that is radioactive, i.e. one having an unstable nucleus, which gives it the property of decay by one or more of several processes.

Cancer Pain Management, Radiotherapy

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R

Randall-Selitto Paw Pressure Test 2091

Radio-Ligand Binding

Definition

A method for detecting the distribution of receptors in tissue sections, based on the use of radio-labeled com- pounds that bind specifically to the receptor. These can then be revealed with autoradiography.

 Opioid Receptors at Postsynaptic Sites

Radiopharmaceuticals

Definition

Radioisotopic medications that emit radiation for diag- nostic or therapeutic purposes including bone cancer pain management.

 Adjuvant Analgesics in Management of Cancer- Rated Bone Pain

Radiosurgical Rhizotomy

Definition

Treatment of TN by a mild injury produced by irradi- ation of the intracranial portion of the trigeminal nerve using focused, MRI guided radiation, using either cobalt (gamma ray) or a linear accelerator as a source.

 Trigeminal, Glossopharyngeal, and Geniculate Neu- ralgias

Radiotherapy

Definition

Treatment of disease by ionizing radiation.

 Adjuvant Analgesics in Management of Cancer- Rated Bone Pain

Raeder’s Paratrigeminal Syndrome

Definition

A combination of pain, ipsilateral oculosympathetic de- fect and ipsilateral trigeminal dysfunction.

 Headache due to Dissection

Ramus

Definition

Ramus refers to a branch; a projecting part.

 Facet Joint Pain

Randall-Selitto Paw Pressure Test

VALERIEKAYSER

NeuroPsychoPharmacologie Médecine, INSERM U677, Faculté de Medécine Pitié-Salpêtrière, Paris, France

kayser@ext.jussieu.fr

Definition

Rat-appropriate mechanical assay based on the use of short-duration stimuli (in the order of seconds). In the course of this pain test, a pressure of increasing inten- sity is applied to a punctiform area on the hind paw, or far less commonly, on the tail. The monitored reactions range from paw withdrawal reflexes (the rat withdraws its paw) to more complex organized unlearned behav- iors (escape or vocalization). The measured parameter is the threshold (weight in grams) for the appearance of a given behavior. Tests using constant pressure have been abandoned progressively for those applying gradually increasing pressures.

Characteristics

The Randall-Selitto paw pressure test (Randall and Selitto 1957) is a sensitive assay, able to show effects for the different classes of antinociceptive agents, at doses comparable to those used for analgesics in hu- mans (refs. in Guilbaud et al. 1999). Its predictability is strong related to situations in which one is trying to understand the basic mechanisms underlying pain, and in terms of identifying analgesic molecules. Re- sults obtained with this assay are reproducible not only within the same laboratory but also between different laboratories. Its advantage is a precise stimulus appli- cation (e.g. right vs. left paw). Further, the test allows simultaneous analysis of the thresholdof response to noxious stimulation of a spinal reflex (withdrawal of the limb) on the one hand, and a centrally pro- cessed reaction (vocalization) on the other (Kayser and Christensen 2000). The method has been helpful especially for assessing mechanical hypersensitivity under varied experimental conditions, such as during different phases in localized inflammation (Kayser and Guilbaud 1987; Kayser et al. 1998). It requires, how- ever, restraining of the rat by hand. Thus, the animals cannot control the intensity or duration of the stimulus.

From a physiological point of view, it seems essential that three parameters in this test can be controlled with some precision by the experimenter: the intensity, the duration, and the surface area of stimulation. These three parameters determine the global quantity of no- ciceptive information that will be carried to the central nervous system by the peripheral nervous system. In healthy rats, this type of mechanical stimulation has a certain number of disadvantages. Firstly, repetition of the stimulus can produce a diminution, or conversely

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2092 Randall-Selitto Paw Pressure Test

an increase, in the sensitivity of the stimulated part of the body; in the latter case this carries the risk that the tissues may be altered by inflammatory reactions that could call into question the validity of repeated tests.

Secondly, there is the necessity of applying relatively high pressures. Lastly, there is a non-negligible level of variability of the responses. With the aim of improving the sensitivity of the test, Randall and Selitto (1957) proposed comparing the thresholds observed with a healthy paw and with an inflamed paw, based on the principle that inflammation increases the sensitivity to pain, and that this increased sensitivity is suscepti- ble to modification by analgesics. The inflammation was induced beforehand by a subcutaneous injection into the area to be stimulated of substances such as croton oil, beer yeast, or carrageenin, the last of these being the most commonly used today. Even though it was found that the sensitivity of the method was improved it was to the detriment of its specificity, be- cause two different pharmacological effects, analgesic and anti-inflammatory, could be confused. However, a comparison in the same animal of responses triggered from a healthy and an inflamed paw allows this problem to be overcome: nonsteroidal anti-inflammatory drugs are inactive on the former, but do increase the lowered vocalization threshold when pressure is applied to the latter (Winter and Flataker 1965). The mechanical stim- ulation used differs notably from the application of von Frey filaments, often almost revered by neurologists, but which has the disadvantage of activating low-threshold mechanoreceptors as well as nociceptors. There are also technical difficulties in applying mechanical stimuli in freely moving rats.

In practice, as illustrated in Figure 1, the paw or tail (Kayser et al. 1996) is jammed between a plane sur- face, and a blunt point mounted on top of a system of

Randall-Selitto Paw Pressure Test, Figure 1 Mechanical stimulation is made using the procedure of Randall and Selitto (1957), with an Ugo Basile analgesimeter: a linearly increasing force is applied via a dome shaped plastic tip (∅ = 1 mm) onto the surface of the hindpaw. The force causing paw withdrawal is quoted, as well as that inducing vocalization (audible squeak).

cogwheels with a cursor that can be displaced along the length of a graduated beam. These devices per- mit the application of constantly increasing pressure and the interruption of the assay when the threshold is reached. When the pressure increases, one can see successively the reflex withdrawal of the paw, a more complex movement whereby the animal tries to release its trapped limb, then a sort of struggle (animal tries to escape, not always observed), and thereafter vocaliza- tion (an audible squeak) (Winter and Flataker 1965).

The stimulus intensity necessary to elicit paw with- drawal from mechanical stimulation, struggle reaction or vocal response from the animal is determined. If the first of these monitored reactions is undoubtedly a proper spinal reflex, although under influence of de- scending supra-spinal inputs, the last two clearly involve supra-spinal structures (Winter and Flataker 1965). It was firmly established in experiments in which the effect of interruption of the anterolateral quadrant of the rat cervical spinal cord, as well as partial lesion of the lateral ventrobasal complex of the thalamus has been determined, using paw withdrawal and vocaliza- tion threshold to paw pressure as the endpoints. Both lesions led to a large enhancement of the vocalization threshold to paw pressure, but did not alter the paw withdrawal threshold (Kayser et al. 1985). Other stud- ies have shown that systemic low doses of morphine, that strongly depressed neuronal thalamic but not spinal responses to noxious stimuli in the rat, produced marked effects in the first but not in the second of these two tests (Kayser and Guilbaud 1990; Kayser 1994).

In our laboratory, a mechanical stimulus was applied using the Ugo Basile analgesymeter (Apelex). This instrument, controlled by a pedal, generates a linearly increasing pressure applied through a dome-shaped plastic tip (1mm diameter) onto the dorsal surface of the paw. The rat is gently held by the trunk, leaving the head and limbs freely exposed. Testing sessions are conducted in a quiet room. Rats are randomly assigned to groups of five or six for a given series of tests, and are not acclimatized to the test situation beforehand. Force is applied until the rat withdraws its limb (withdrawal threshold to paw pressure) and/or squeaks (vocalization threshold to paw pressure). The withdrawal reflex that occurs before vocalization is prevented by smoothly holding the rat’s hind paw in position under the pusher until vocalization. The two paws are tested consecu- tively in each rat. The sequence of sides is alternated between the animals to prevent ‘order’ effects. For each rat, a control threshold (mean of two consecutive stable thresholds expressed in grams) is determined before injecting the drug. After drug administration, nociceptive pressure thresholds are measured every 5 or 10 min, until they have returned to the level of the control values. Thus, each rat is its own control.

Results are then expressed in grams or as a percentage of the control values. Based on the principle that the

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