Pergamon

SURVEY ARTICLE

LUMBAR FACET PAIN: BIOMECHANICS, NEUROANATOMY AND

NEUROPHYSIOLOGY

John M. Cavanaugh,* A. Cuneyt Ozaktay ,* H. Toshihiko Yamashita? and Albert 1. King*

*Wayne State University, Bioengineering Center Detroit, MI 48202, U.S.A.; and TDepartment of Orthopaedic
Surgery. Muroran City General Hospital Muroran, Hokkaido 051, Japan

Abstract-Idiopathic low back pam has confounded health care practitioners for decades. Although there has been
much advance in the understanding of the biomechanics of the lumbar spine over the past 25 years, the cellular and
neural mechanisms that lead to facet pain are not well understood. An extensive series of experiments was
undertaken to help elucidate these mechanisms and gain a better understanding of lumbar facet pain. Biomechanic
and neuroanatomic studies were performed in human cadaveric facet joints and neurophysiologic studies were
performed in New Zealand White rabbits. These studies provide the following evidence to help explain the
mechanisms of lumbar facet pain: (1) The facet joint can carry a significant amount of the total compressive load on
the spine when the human spine is hyperextended. (2) Extensive stretch of the human facet joint capsule occurs
when the spine is in the physiologic range of extreme extension. (3) An extensive distribution of small nerve fibers
and free and encapsulated nerve endings exists in the lumbar facet joint capsule, including nerves containing
substance P, a putative neuromodulator of pam. (4) Low and high threshold mechanoreceptors fire when the facet
joint capsule is stretched or is subject to localized compressive forces. (5) Sensitization and excitation of nerves in
facet joint and surrounding muscle occur when the joint is inflamed or exposed to certain chemicals that are
released during injury and inflammation. (6) Marked reduction in nerve activity occurs in facet tissue injected with
hydrocortisone and lidocaine. Thus. the facet joint is a heavily innervated area that is subject to high stress and
strain. The resulting tissue damage or inflammation is likely to cause release of chemicals irritating to the nerve
endings in these joints, resulting in low hack pam. Copyright ‘1’ 1996 Elsevier Science Ltd.
Keywor& Low back pain; Facet joint: Nociceptors: Inllammation Substance P.

LUMBAR FACET JOINT ANATOMY AND NEL’ROANATOMY message of pain. The pain generators are usually the free
nerve endings of the pain fibers, which are the smallest
The lumbar facet joints are also called the sonratosensory neurons. They are either small myelinated
zygapophysial joints They are paired synovial joints that A-delta fibers, l-5 pm in diameter or unmyelinated
join the vertebral arch of one vertebra to the arch of the C fibers, 0.5-2 pm in diameter, and their endings are
next vertebra. In the lumbar area in the standing subject unencapsulated. These are also called group III and IV
the facet joint plane is vertically oriented with the plane fibers respectively (Guyton, 1981). Under normal condi-
between sagittal and coronal when looking down the tions, pain fibers (nociceptors) have high mechanical thre-
spine. sholds That is, they fire only when the stress to them is
The tissues in the spine itself have a complex pattern of noxious. Under pathologic conditions such as inflamma-
innervation (Fig. 1, from Paris, 1983). The facet joint is tion, chemical mediators sensitize the nerve endings and
innervated by medial branches of the dorsal rami that high levels of stress or strain are no longer required for
exit the intervertebral foramen (Pedersen cr al.. 19.56). them to fire; they can fire spontaneously or in response to
Typically, the joint is innervated from a branch at the low levels of stress and strain.
same level and a branch originating front the foramen
above (Bogduk, 1983)
CLINICAL EVIDENCE FOR FACET PAW

SOURCES OF PAIN GENERATION

The existence of the facet syndrome is controversial.
Hirsch er al. (1963) and Mooney and Robertson (1976)
For a region of the lumbar spine to be a source of pain
produced low back pain with radiation to the thigh by
it must be innervated by nerve fibers that transmit the
injecting hypertonic saline into facet joints. A review of
the literature by Helbig and Lee (1988) indicated that
facet block had a 5&60% success rate and facet rhyzoly-
Received in final form I5 December 1995.
Author correspondence to: John M. Cavanaugh. M.D.. sis similar results. Kuslich et al. (1991) and Kuslich and
Wayne State University, Bioengineering Center. 818 W. Ahern (1994) performed a pain-provocation study in 193
Hancock, Detroit, MI 48202. U.S.A. awake patients undergoing decompressive lumbar spine

Ill7
1118 J. M. Cavanaugh et al.

Sympathetic cham

Branch under anterior

longitudinal ligament
Ascending branch
sinuvertebral nerve
gray ramus
to disc
Sinuvwtebral
to disc
b Gray ramus

Branches from
ramus to disc
Medial branch of

facet branch
to sacrotliac ot post.
pnmafy ramus
Fig. 1. Segmental innervation of the lumbar spine (from Stanley V. Paris (1983) Orthop. Clin. North ,4m. 14,
385410, with permission). Facet und erector spinae muscle innervation: The posterior primary ramus sends
medial branches to the facet at the level of nerve exit and to the facet below. Per some investigators there is
also a branch to the facet above (as shown). There are also medial branches to muhifidus muscle.
Intermediate erector spinae muscles (longissimus) are innervated by the intermediate branches of posterior
primary rami. Lateral erector spinae (iliocostalis) are innervated by lateral branches of posterior primary
rami, which also innervate cutaneous tissue (see Bogduk, 1983). Interuertebral disc innervation: Branches
from the sympathetic chain innervate the lateral and anterior portions of the disc above and below. The
recurrent sinuvertebral nerve which is formed from the gray ramus communicans and mixed spinal nerves
innervates the posterior and postero-lateral portions of the disc at two levels inside the spinal canal. The
ventral ramus sends small branches to the disc at the level of nerve exit

surgery for disc herniation and/or spinal stenosis under
progressive local anesthesia using 1% lidocaine. Even
though disc and nerve roots were the main sources of
pain, 54% of patients had some sensation when the facet
capsule was stimulated and 20% had significant pain. On
the other hand, Jackson et ul. (1988) performed facet
injections on 454 patients without root tension signs and
in whom conservative therapy had failed. A set of vari-
ables to select patients in whom injections were successful
could not be determined. Lilius et a/.. (1989) found that
injection of normal saline was as effective as injection of
steroids and lidocaine to ease facet pain. Schwarzer et al.
(1994) performed facet joint injections or medial branch
blocks in 176 consecutive patients. Those who responded
to the first series of blocks with lignocaine were given
a confirmatory block with longer-acting bupivacaine.
Fifteen percent had a positive response to both with
longer duration relief after bupivacaine and were thus
deemed to have facet pain. In the study by Schwarzer
et ul. (1994) the set of clinical features proposed by Fair-
bank et ul. (1981) or Helbig and Lee (1988) to diagnose
facet pain did not reliably discriminate those with pain of
facet origin from those with pain of another origin. These
studies demonstrate that the facet syndrome is difficult to
diagnose and the fact that patients respond to placebo
injections into the facet makes the cause in many cases
uncertain. However, the dual anesthetic studies of
Schwarzer et u[. (1994) demonstrate that the facet
joint is the source of low back pain in a percentage of
patients.
Our studies were undertaken to understand better the
mechanisms of facet pain and reveal the following: The
facet joint capsule is richly innervated and can undergo
extensive stretch under physiologic loading. The nerves
are activated by capsular stretch and by neurogenic and
non-neurogenic mediators of inflammation (substance P,
bradykinin, PLAZ) that may contribute to the cycle of
pain when there is facet joint pathology.
BIOMECHANICS STUDIES
Wayne State University had a unique vertical acceler-
ator housed in an elevator shaft which could propel
a seated cadaver up the shaft to simulate the first 200 ms
of an aircraft ejection. Ewing et al. (1972) proposed that
 Lumbar facet pain
the articular facets were motion limiters which played
a role in injury prevention. When hyperextension was
induced in the lumbar spine, the facet load persisted
throughout the ejection pulse and there was an 80%
increase in the g-level required to fracture the vertebral
body (an increase from about 10 to 18 gs). Tests carried
out as a result of this hypothesis led to the discovery by
Prasad et a/. (I974) of a facet load which was transmitted
down the spine in parallel with the load through the disc
and endplate. The key transducer was an intervertebral
load cell (IVLC) inserted above a lumbar disc, after an
inferior portion of the vertebral body above it was cut
out. The difference between the load measured by the
IVLC and the inertial load seen by the spine at that level
was termed ‘facet load’ because no other structure in the
spine was available to carry this load.
A quasi-static study using isolated lumbar segments
consisting of three vertebrae and two discsalong with the
IVLC was carried out by Yang and King (1984) to
quantify this facet load as a function of the eccentricity of
the applied load relative to the disc center. It was ob-
served in these tests that when there was significant facet
loading, the inferior tip of the facets bottomed out on the
laminae below and acted as pivots for the entire vertebra
to rotate rearward, causing a visible stretch of the su-
perior portion of the facet capsules,with extravasation of
blood onto the external surface of the capsule. El*Bohy
et ~1.(1989) extended the study t,o include the simulation
of extensor muscle action (Fig. 2) and showed that facet
loads existed in the erect posture and that they increased
Fig. 2. Illustration of the experimental setup for biomechanical studies of facet joint loading (from El-E3ohy
et uL, 1989). A pair of wire cables, each with turnbuckle and load cell, simulated extensor muscle loadiug.
when a simulated weight Iocated about 34 cm in front of
the spine was added to the spine.
The next obvious biomechanical experiment was to trj
to quantify the capsular stretch first noted by Yang and
King (1984). A stereophotogrammetric system consisting
of two video cameras was set up to track the motion of
a set of 800 pm diameter spherical targets which were
attached to the surface of a facet capsule by means of
a skin adhesive, as reported in Schultz ef a6.(1988). Large
strains were found in many of the specimens tested when
the segment was placed in extension (El-Bohy er 6&l.,1987).
The stretch per N m of applied moment is shown in Table
1 for both extension and flexion. The peak moments were
approximately 18 Nm for extension and 24 N m for
flexion. The stretch was measured as the percent change 111
length per original length between markers”
It should be noted that the measured strains were
highly localized and the applied loads were nc>t large
enough to cause rupture of the capsules or any visible
injury. However, stretch of the capsuIe was visible to the
naked eye very much like the stretching of a rubber band,
often when the spine was in extension but not when the
spine was in flexion. It was also observed that in exten-
sion there was bony contact of the tip of the facet with the
lamina below and that a rearward rotation of the su-
perior portion of the inferior articular process of the facet
occurs, causing the superior portion of the capsule to be
extensively stretched. The external geometry of the
superior portion of the facet was apparently a major
factor in determining the magnitude of the stretch and it
A Anterior
B Sody wetght
0 Dead wetght
L Load ceN
P FMterlor
.S Sptfle segment
T Turnbuckte
1120 J. M. Cavanaugher ~1.

Table 1. Maximum tensilefacet capsulestretchdata (%/Nm)

Extensiontests Flexion tests
CadaverNo. X-axis Y-axis Z-axis Resultant X-axis Y-axis Z-axis Resultant
400 7.1 a.7 5.3 12.4 0.6 0.2 0.1 0.6
464 4.8 5.5 8.2 11.0 0.1 0.4 0.3 0.5
807 3.3 2.5 6.4 7.6 0.4 0.6 0.3 0.8
329 7.4 6.3 0.2 9.7 0.8 2.6 1.9 3.3
455 1.3 3.9 1.3 4.3 0.3 1.3 0.3 1.4
490 0.8 2.5 4.7 5.4 2.2 4.5 I.2 5.2
2 0.8 7.4 7.0 10.2 1.3 3.5 6.4 7.4
117 0.8 6.6 6.6 9.4 0.9 7.1 1.3 7.3
34 12.4 21.0 21.1 32.2 2.0 0.3 3.0 3.6

SD 4.0 5.6 6.0 7.8 0.7 2.4 2.0 2.6

cv 93.8 78.4 88.7 77.5 104.5 122.8
AVG 4.3 7.2 6.8 11.4 1.0 2.3 1.6 3.3

Note: X-axisis directedanteriorly in the transverseplane; Y-axisis directedlaterally to the left in the
transverseplane;Z-axisis directedsuperiorlynormal to the transverseplane;SD is the standarddeviation;
CV is the coefficientof variation; AVG is the average.

is not surprising to find a large degree of variation in the
data. An arthritic facet with bony build-up of its
anteroposterior thickness can causea much larger stretch
than a thin facet. Not everyone encounters pain when the
spine is put into hyperextension.
These results form the biomechanical basis for a hy-
pothesis that the facet joint capsule is a source of low
back pain and that the pain may arise from large strains
in the joint capsule that cause pain receptors to fire. To
test this hypothesis, the following neuroanatomic and
neurophysiologic studies were performed.
NEUROANATOMIC STUDIES
Eight whole facet joint capsules from L2/L3 to L5/Sl
were excised from five unembalmed adult cadavers. Sil-
ver impregnation using a whole mount staining method
(Winkelman and Schmit, 1959) along with gold toning
was used to stain the specimens. Silver nitrate and gold
toning display the nerve structures by staining of neuro-
filaments within nerve fibers and endings (Gambetti
et ul., 1981; Potter, 1971). More than 100 small group III
and IV nerve fibers were found in both outer and inner
capsular layers (Ozaktay et al., 1991). Numerous free
nerve endings [Fig. 3(a)] and Ruffini-type endings were
also seen along with an occasional Pacinian-type cor-
puscle [Fig. 3(b)]. It is the free nerve endings that are
likely to serve a pain function (Wyke, 1982). The encap-
sulated endings (Ruffini, Pacinian) serve the function of
mechanoreception for position senseor movement. Stud-
ies in the rabbit capsule demonstrated similar types of
nerve endings (El-Bohy, 1990).
NEUROPHYSIOLOGIC STUDIES
The next step was to perform nerve recordings from
nerves innervating the facet joint. The previous work
done by others in the knee joint (Grigg and Hoffman,
1982; Grigg ef al., 1982, 1986; Schaible and Schmidt,
1983a,b) was used as a model in these studies.
Surgery
Adult male New Zealand White rabbits (3-4 kg) were
anesthetized with ketamine hydrochloride, xylazine and
butorphanol, i.m. The animals were hydrated with
lactated Ringers through a marginal ear vein. A lumbar
laminectomy was performed to expose the lumbar dorsal
roots of interest and the dorsal roots were cut at their
proximal ends, split and kept in mineral oil at 37’C
(Fig. 4). The left L5/L6 or L6/L7 facet joints were studied
and recordings were made from the corresponding L5 or
L6 dorsal roots.
instrumentation
The data were amplified (Model 1700 Differential A-C
Amplifier, A-M SystemsInc, Everett, WA), monitored on
an oscilloscope (Model No. 5113, Tektronix Inc,
Beaverton, OR) and stored using an analog data recorder
(MR-30, TEAC Corporation, Montebello, CA). The data
were later digitized and analyzed with a computer
software system (R.C. Electronics ISE-16E, Goleta, CA).
Experiment protocol to characterize sensory
nerve function
The following procedure was used to characterize the
response of facet joint and adjacent muscle units to local
pressure,capsule stretch an inflammatory chemicals. The
split dorsal roots were draped one at a time over
platinum recording electrodes (Fig. 4). The tissue of inter-
est was searched with l-2 mm diameter blunt glass rods
for mechanosensitive units. When the responsive area
was identified (the receptive field), it was stimulated with
pressure aesthesiometer hairs (Pressure Aesthesiometer,
Stoelting Co., Chicago, ILL) to determine the mechanical
threshold at which the nerve would begin to fire. These
nylon hairs are similar to von Frey hairs and ranged from
0.20 to 28 g in buckling strength. Previous work on the
 Lumbdr facet pain

Fig. 3. (a otomi crograph showing free nerve endings with a parent nerve fiber 2 pm in diame
I hL [man lar fa( :et joint capsule (scale bar = 25 pm). (b) A Pacinian-type corpuscle with its distu
III ski carat Ice in a human lumbar facet joint capsule. (Scale bar = IO0 pm. 250 x 550 jirn m
1122 J. M. Cavanaugh et al.

with CVs ranging from 20 to 70 m s- ’ as group II (larger,

FMTweReccrder
myelinated A-beta fibers).

Facet joint and muscle units in control animals

Stimulation
Facet Jatnt tsoleteci Inferior
tipSUl~
Artlculer Pmceas
Fig. 4. IlluskaGon of experimental setup for facet joint record-
ings. In capsular stretch studies the inferior L5 or L6 articular
process was cut and freed from the surrounding lamina so that it
could be pulled in medialHatera1, dorsal-ventral and
caudal-rostra1 directions to stretch the facet joint capsule and
activate units. The instrumentation for all experiments was as
shown. The analog data were later downloaded through an A/D
converter for computer analysis.
knee joint suggested that 6 g and higher was high
threshold (Schaible and Schmidt, 1983a). The receptive
field was stimulated electrically with pulses of 0.1 ms
duration using a metal bipolar electrode to obtain
conduction velocities (CVs). Often voltages greater than
10 V were required to evoke action potentials. CVs were
calculated by measuring the distance in millimeters (mm)
between stimulating and recording electrodes and
dividing this by the onset latency of the evoked response
in milliseconds (ms). Alternatively, CVs were obtained by
recording from two bipolar platinum wire electrodes and
measuring the latency for the action potential to travel Spine loading studies
from one electrode to the next. Fibers conducting at less Twenty-four in uitro experiments were done in order to
than 2.5 m s - ’ were classified as group IV (unmyelinated determine if facet joint receptors would respond to spine
C fibers), those with CVs ranging from 2.5 to 20 m se1 as loading (Avramov et al., 1992). The abdominal aorta of
group III (finely myelinated, A-delta fibers) and those the anesthetized rabbit was cannulated and perfused with
(Yama-shita et al., 1990, 1993b)
Thirty mechanosensitive units were identified at the
facet joint and 27 others in the muscles and tendons near
their insertion into the facet. Of the 30 units at the facet
joint, 13 were in the capsule, 15 in the border regions
between capsule and muscle or tendon, and two in the
ligamentum flavum (Fig. 5). Of the 30 units in the facet
joint, two units had CVs < 2.5 m s- ’ (group IV), 17 units
had CVs of 2.5-20 m s- ’ (group III) (Fig. 6), and 11 units
had CVs > 20 ms-’ (group II). Nine units had
thresholds > 6.0 g, 17 units had thresholds < 6.0 g, and
four units were not examined. Eight units responded to
joint movement caused by pulling on the isolated L5
lamina. Five of these were in the medial aspect of the
facet joint. These units were most responsive to l-2 mm
of caudal-to-rostra1 stretch. The two units in the
ligamentum flavum were most responsive to
ventral-to-dorsal stretch. Of the 27 units in muscle and
tendon, one unit had a CV < 2.5 rns-’ (group IV),
4 units had CVs of 2.5-20 m s- ’ (group III), and 22 units
had CVs > 20 rns-l (group II). One unit had
a threshold > 6.0 g and 26 units had thresholds < 6.0 g.
Thus, the facet joint contained a much higher propor-
tion of high-threshold, low conduction velocity units
than muscle. It is these units that are likely to serve as
a pain function. These studies demonstrated that some
units in the joint capsule were indeed responsive to
stretch. However, the stretch was applied through
a somewhat non-physiologic means (pulling on a surgi-
cally isolated joint) so the next step was to determine
whether spine loading would cause capsular stretch that
would cause facet joint units to fire.

muscles and tendons facet joint capsule

Fig. 5. Map of receptive fields in rabbit facet joint and adjacent tissue (modified from Yamashita et al.,
1993b). Squares denote units with thresholds less than 6 g, circles denote units with threshold greater than
6 g. If the unit responded to stretch the symbol is hollow.
 Lumbar facet pain

Fig. 6. Example of discharge from an A-delta (small myelinated) fiber. L&t tra shows the response to
mechanical pressure applied with a glass probe. Right trace shows the same unit reaponding to an electrical
pulse applied to the receptive field every second. The latency between electrical stimulus and action
potential response was used to determine conduction velocity.

CM

a.“.
.v* ,.“. --.--

Fig. 7. 1r1 uitro spine loading chamber. Oxygenated Krebs solution was perfused through the abdomimti
aorta. Axial load, measuredby a load cell,wasrecordedsimultaneouslywith neuronal dischargerecorded
from dorsalrootlets,usinga bipolar recordingelectrode(From Avramov er a[., 1992). AA, abdominal aorta:
AC, acrylicchamber,filled with Krebs solution;CAC, caudalclamp;CEC.cephaladclamp: FJ,facetjoint.
FJC, facet joint capsule; LC, load cell; LD, loading device; L3, 3rd lumbar vertebra; L7. 7th lumbar
vertebra;PC, perfusingcatheter;RE, recordingelectrode.

Krebs soluGon oxygenated with 95% OZ-5% COZ. The
lumbar spine was removed with bone rongeurs and
placed in a chamber perfused with the same solution
(Fig. 7). Receptive fields were characterized and nerve
recordings made for 2-3 h as the spine was loaded in
tension and compression. A 100 pound load cell (Entran
Devices ELF-100, Faifield, NJ) recorded tensile and
compressive loads.
In these experiments a typical response was a vigorous
multi-unit discharge during loading. During compressive
loading the spine underwent dorsal-lateral bending that
caused the facet joints to articulate along the joint plane,
stretching the facet joint capsule. Loading excited both
units with spontaneous activity, as well as units that were
silent before loading was initiated. Three patterns were
observed: (1) short duration bursts during onset or
change in loading (phasic-type responses),(2) prolonged
discharges that began during low levels of loads of
300-500 g (slowly adapting, low-threshold mechanore-
ceptors), and (3) prolonged discharges activated by
higher loads of 3-5.5 kg (slowly adapting high-threshold
mechanoreceptors). It is this iatter response which
strongly suggests activation of pain fiber&. Fourteen
smalI myelinated or nnmyeIinated fibers (groups III and
IV) were found around the facet joint. Figure 8 illustrates
the response of a low-threshold unit af the tip of the facet
joint that also responded to spinal compression. It was
often not possible to track the response of these indi-
vidual units to spine loading as this loading naturally
elicited firing from many nerves.
7% ejkts qfjizcet joirtt it7jummutiott 0t1 nets uctirilj~
In both the in Vito and in &ro experiments described
above, nerves typically stopped firing after the mechan-
ical stimulus was removed or shortly thereafter. even if
the stimulus was clearly noxious. Thus, thcsc results
demonstrate that capsular stretch could cause the onset
of facet pain but does not explain its persistence. It is
likely that obvious tissue damage (i.e. tearing of’muscle or
capsule) would result in persistent discharge c;tused in
1124 J. Ivl. Cavanaugher ul.
a of inflammatory mediators in facet joint pain was studied
b response to joint movement was recorded and compared
Fig. 8. Response of a unit at the tip of the facet joint to electrical
stimulus, local applied pressure and spine loading (From
Avramov ef al., 1992). (a) Evoked response due to stimulating
the receptive field with a bipolar electrode. (AP = action
potential, SP = stimulus pulse). (b) Response due to stimulation
of receptive field with 0.93 g von Frey hair (up arrow = onset of
stimulus, down arrow = offset of stimulus). (c) Simultaneous
recording of neuronal discharge (upper trace) and load as
measuredby the load cell (lowertrace).An initial peak of 350g
(at dashed arrow) activated this low threshold unit. Higher
threshold units typically did not respond until compressive
loads reached 3000 g or more.
part by the release of algesic chemicals from damaged
and inflamed tissue. This is likely to occur when there is
joint motion well beyond physiologic limits, such as
cervical facet joint strain in whiplash injury or medial
collateral ligament tear in knee injury. The possible role
next as a step in understanding the persistence of low
back pain. These studies focused on neurogenic and
non-neurogenic inflammatory mediators. Kaolin (a silica
product) and carrageenan (a seaweed product) are com-
monly used to produce an acute tissue inflammation
which results in a release of histamine, bradykinin and
prostaglandins into extracellular tissue. These algesic
(pain-producing) chemicals can excite and/or sensitize
nerve endings (Berberich et al., 1988; Grigg et u/., 1986;
Rang et al., 1991). To our knowledge, the response of
sensory nervesto inflammation had never been studied in
lumbar spine tissues.
In initial studies in seven rabbits the left L5/L6 or
L6/L7 facet joint was injected with 0.1 ml of 2% car-
rageenan and 0.1 ml of 4% kaolin. The nerve discharge in
to control animals (Cavanaugh et u/., 1990). In these
studies units were found in multifidus, rotatory and inter-
mamillary muscles, or in the facet joint capsule and
border regions at the junction of capsule and muscle
tendon insertions. For 42 units, receptive fields were
identified with pressure aesthesiometer hairs or glass
rods. For 30 units thresholds ranged from 0.05 to 17.3 g
with the lower threshold units primarily in muscle and
the higher threshold units at the facet joint. Most of the
units in this study were in group II ( > 20 m s- ‘) or
group III (2.5-20 m se ‘). Spontaneous discharge rates
(SDRs) were monitored for 21 units in inflamed tissue
and 21 units in controls. The average SDR was 18.1 units
per second (range &SO) in the inflamed joints and 9.3
units per second (range O-28) in the controls. The units in
control animals were often quiet unless stimulated mech-
anically while units in inflamed tissue often had elevated
baseline discharge rates. In inflamed joints, there
occurred vigorous multi-unit response to stretch by
moving the facet joint approximately 1 mm in caudal-
rostral, ventral-dorsal and lateral-medial directions.
In a later study in 15 rabbits the mechanical threshold
and CV were determined for receptive fields in the L5/L6
facet joint capsule or adjacent muscle. Then 0.1 ml of 2%
Type II carrageenan (Sigma, St. Louis, MO) in 0.9%
NaCl was injected into the receptive fields and the
discharge was monitored for 2 h and 30 min (Ozaktay
et ul., 1994). At the end of these experiment the tissue
was histologically examined using hematoxylin and
eosin (H&E) staining.
In this study spontaneous discharge rate showed in-
creasesthat consisted of two phases: a first phase from
0 to 30 min and a second phase from 45 to 150 min
(Fig. 9). The time course of single units, identified as
groups II, III, IV and silent units, was investigated. Units
which were previously silent appeared in the first 15 min
and persisted beyond 75 min. Thresholds of the
characterized units ranged from 1.2 g to glass rod and
decreased with time, demonstrating that inflammation
sensitized these units to mechanical pressure. Histologic
examination revealed inflammatory changes in
carrageenan injected tissues,vasodilatation and edema in
 Lumbar facet pain I f-5
h-..

a : b: : : :

460 e

-15 -5 0 I 5 10 15 30 45 60 75 90 105120135150
0 TIME (Inin)

Fig. 9. Representative one second recordings of multi-unit discharges as taken from a carrageenan injected
experiment (from Ozaktay et al., 1994); (a) 5 min before the injection; (b) S min after the carrageenan
injection; (c) 90 min after the carrageenan injection; (d) 150 min after the carrageenan injection; (el
multi-unit discharge rate per second from the same experiment computed in a histogram. The histogram
bars corresponding to Figs 9(ak(d) are noted.

synovial capsule and additionally, leukocyte infiltration eleven-amino-acid neuropeptide released from small
in the perivascular space within surrounding muscle tis- nerve fibers. It has been shown to be released from nerve
sue. In contrast, in isotonic saline injected control experi- endings in the knee .joint (Yaksh. 1988). Substance
ments there were no significant changes observed in the P causes vasodilatation. plasma extravasation and re-
electrophysiologic or histologic studies. lease of histamine from mast cells f Rang <f ul., 1991).
There are obvious clinical implications to the fact that These are important in the inllammatory cascade which
peripheral nerve endings become sensitized by chemical can prolong pain. Substance P is also released at nerve
mediators of tissue damage and inflammation. Inflamed synapses in the dorsal horn of the spinal cord to facilitate
joints have an ongoing background nerve discharge that action potential transmission in spinal cord pain path-
can cause constant pain at rest and sensitized nerve ways (Coderre ef Q/., 1993; Rang cr ul., 1991) Substance
endings that can cause increased pain during ordinary P has been demonstrated in nerves of lumbar spinal
movements. Thus, facet nociceptors that would normally tissues (Korkala et u/.. 1985) and in our laboratory in
only fire when mechanical stress is clearly noxious will small nerve fibers of the facet joint (El-Bohy cf ul., 198l.l).
me at much lower stresses in the presence of these chem- However, its effect on lumbar spinal tissue nerve activity
icals and maintain a background discharge even without had never been studied.
mechanical stress. This peripheral sensitization is In 15 rabbits a study was undertaken to examine how
a mechanism for the persistence of pain. substance P alfects the mechanosensitive afferent units
identified in the lumbar facet joint and adjacent tissues of
the rabbit (Yamashita c>r u/., 1993a). Substance P was
The carrageenan studies demonstrated that tissue applied to the receptive fields of the units by means of
intktmmation had a profound effect on the mechanical microinjection. and aherent activity of the units was
sensitivity and discharge rate of facet joint units. Another recorded from dorsal root filaments. Changes of afferent
type of tissue inflammation which is more subtle is called discharge rates and l,on Frey thresholds were measured
neurogenic inflammation and is the result of inflammatory for 30 min.
chemicals released from the nerves themselves. One of the Most of the units (,83,3X) showed an increase in SDR
most studied neurogenic mediators is substance P, an after the injection of IO I[& substance P into the receptive
1126 J. M. Cavanaugh et al.

Fig. 10. Excitation of facet joint units to injection of 10 ng substance P (SP) into the receptive field: (A)
2 min before SP application; (B) During SP application. (CHF) 30 s, 1 min, 5 min and 10 min after SP
application (From Yamashita et al., 1993a).

field; 54.2% of the units showed immediate onset
(Fig. 10) and 29.2% of the units showed slow onset of the
excitation. One-third of the units showed decreased von
Frey thresholds after the application of substance
P (evidence of sensitization). Substance P had an excita-
tory effect on 81.8% of the units with thresholds > 5.0 g
and conduction velocities < 30 m s- ’ that may serve as
nociceptors, and 84.6% of the units with thresholds
< 2.0 g which may serve as proprioceptors. These stud-
ies suggest that release of substance P may contribute to
transmission of both nociceptive and proprioceptive sen-
sations. In our studies, substance P may have had a direct
effect on the nerve endings in paraspinal tissue, or acted
indirectly through its influence on vasodilatation, plasma
extravasation and histamine release.
Effects of PLA2 on nerve response in the facet joint
Phospholipase AZ (PLAZ) is another chemical that
may contribute to low back pain. It hydrolyses the sn-2
fatty acid in membrane phosphohpid bilayers to produce
arachidonic acid. In turn, prostaglandins and related
eicosanoids are synthesized from arachidonic acid
(Bomalaski and Clark, 1993). This can lead to inflammat-
ory tissue responses.PLAZ may play a role in arthritis as
increased amounts have been found in synovial inflam-
matory effusion (Pruzanski and Vadas, 1991). Saal et al.
(1990) found that herniated human lumbar disc contains
high levels of PLAZ and its activity is 20- to lOO,OOO-fold
more active than PLAZ from other pathologic tissue.
Meyers et al. (1992) showed that human disc and snake
venom PLAz are structurally similar and show similar
neurotoxicity when injected in rat sciatic nerves. There
had been no previous study of the effects of PLAZ on
nerve discharge. Because of this and because PLAZ has
been found in high concentrations in pathologic discs
and rheumatoid joints, such a study was carried out in
our laboratory.
Ozaktay et al. (1995) injected 400, 750 or 1500 U of
PLAZ (Baja naja venom, Sigma, St. Louis, MO) in
buffered carrier solution (100 ~1,pH 7.5,50 mM HEPES,
7 mM CaCIX, 150 mM NaCl) into the receptive field of
the lumbar facet joint or surrounding muscle in 18
anesthetized rabbits. The carrier solution was injected as
controls in four experiments. The threshold and unit
activity was followed for 90 min for later computer
analysis.
Multi-unit data
Only 1500 U PLAZ injections (n = 5) produced signi-
ficant decreasein spontaneous activity of nerve discharge
over time. At 30 min, the characterized units were no
longer mechanically responsive. In three of four experi-
ments using 750 U PLAZ, the nerve discharge increased
in response to mechanical stimulation at 30 min and re-
mained at elevated discharge rates over time. After 400 U
PLAr (n = 5) or control (n = 4) injections, spontaneous
activity did not show any significant changes over time.
Single unit data
Myelinated A-beta fibers (group II, n = 8) showed
significant decreasein their activity after injection of 750
and 1500 U PLAZ. Myelinated A-delta fibers (group III,
n = 8), which may signal pain, became mechanically
excited 30 min after 750 U PLAZ injection. Two units
that were neither spontaneously active nor mechanically
responsive before PLAZ injection were evoked
mechanically 30 min after injection of 750 U PLAZ, and
remained spontaneously active over time. These may be
‘silent nociceptors’ as described by Schaible and Grubb
(1993).
 Lumbar facetpain ’%I’7
‘.

The enzymatic activity of pLAZ has been hypothesized three months). Based on the usual time course of tissue
either directly or indirectly to alter cellular function, injury, inflammation and repair, acute traumatic strain in
induce the releaseof cellular or lipid mediators of inflam- facet joint capsules could lead to acute or subacute low
mation or disrupt cellular and tissue integrity leading to back pain. This is supported by our studies.
injury (Vadas ef ui., 1989). In our studies, neurotoxicity The potential for acute traumatic strain in the lumbar
was demonstrated in response to very low doses of snake facet joints is suggested by the capsular stretch studies of
venom PLA1 injections on facet capsule receptive fields. El-Bohy et a!. (1987). The resulting tissue injury and
This appears to be dose related, since 1500 U injections inflammation can cause prolonged nociceptor excitation
resulted in greater reduction in nerve activity than 750 U as in our neurophysiology models. This peripheral sensit-
injections. In fact, 750 U initially caused nerve excitation.ization (Rang et ui., 1991) can lead to a sensitization of
These data establish electrophysiologic evidence of po- nerves in the spinal cord termed central sensitization
tential inflammatory and neurotoxic roles for PLA1 (Coderre et al., 1993; Jesse1and Kelley, 1991) contribu-
(Ozaktay et al., 1995). ting to persistent pain. The sensitization of nerves to
facet or muscle may also lead to reflex muscle spasm.
The rwurophysiolo~gy qj’cwti-injlammatory and Stimulation of mechanoreceptors of the lumbar facet
unffkysic~ uqfxfs caused reflex nerve response in the contralateral side in
Previous investigators have shown that facet joint pain our rat model (Cavanaugh et al., 1989), presumably in
can be successfullyrelieved with injection of an analgesic motor neurons that can play a role in reflex muscle
into the facet joint. However, Lilius et al. (1989) reported contraction.
that injection of normal saline was as effective as On the other hand, the physiologic basis for chronic
injection of steroids and lidocaine to ease facet pain. low back pain that does not resolve in two or three
Schwarzer et al. (1994) have proposed that to insure that months in uncertain, although neuroplastic changes in
one is dealing with true facet pain, that the pain be the spinal cord after prolonged nociceptive input
relieved with both a short acting analgesic (lignocaine) (Coderre et & 1993) and focal areas of nerve demyelina-
and a longer acting analgesic (bupivacaine). Using this tion and neuroma formation (Devor, 1994) provide com-
criterion, 15% of a seriesof patients were demonstrated pelling explanations. Another possible source of chronic
to have low back pain of lumbar facet origin. low back pain of facet origin is osteoarthritis. Substance
With our animal model, we investigated the response P containing nerve fibers have been reported in osteoar-
of lidocaine and hydrocortisone succinate applied to thritic facet joints in subchondral bone erosion channels
paraspinal muscle, facet joint and dorsal roots. Hydro- (Beaman et a/., 1993). Releaseof substance P from nerve
cortisone sodium succinate (0.1 ml, 50 mg ml- ‘) applied terminals can contribute to the cycle of pain. Since the
directly to the roots caused immediate cessation of all facet joints carry a significant load in compression plus
nerve activity typically for over 30 min (Cavanaugh and extension (Yang and King, 1984) it is plausible that they
Weinstein, 1994). Lidocaine and hydrocortisone applied are a locus of persistent pain in facet osteoarthritis. The
to facet joint receptive fields showed a similar immediate mechanisms of chronic low back pain and chronic pain in
decreasein spontaneous nerve activity (Cavanaugh et u/.. general need further study.
1990). In related work in which saline or buffer controls
were injected into receptive fields, we did not observe the AcknowLedgemenrs-The work reported in this paper was sup-
same decrease in discharge as with hydrocortisone or ported by NIH Grant Nos. GM 20201, NS 28994 and AR 41739.
lidocaine. Obviously, the placebo effect of normal saline The significant contributions of Drs Avram Avramov. Dimitar
Blagoev, Ahmed El-Bohy, Ashraf El-Bohy, Thomas V. Getchell.
injections is not addressed in our model. Qing Hang Li and King Hay Yang to this research arc grafefully
Based on the neuroanatomic and neurophysiologic acknowledged. In addition, we would like to thank Professor
data any technique to ease the patient’s pain through Peter Grigg of the University of Massachusetts who was kind
facet injections must include the facet capsule as an enough to provide us with training in his techniques for record-
ing from somatosensory afferents in the knee joint.
injection site. We have demonstrated the efficacy of injec-
tion into the capsule and surrounding tissue in the rabbit
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