Anatomy and Physiology of Pain Principles of Pain Spinal Cord Stimulation Intrathecal Drug Delivery Selective Spinal Cord Lesioning Neuroanesthesia

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In the 1960s, a large number of neurophysiologic investigations proved that the dorsal horn was the primary level of modulation of pain sensation. This idea was popularized in 1965 through the gate control theory, which drew neurosurgeons’ attention to this area as a possible target for pain surgery. Neurostimulation of the primary afferent neurons was developed to enhance the inhibitory mechanisms of the spinal cord. Conversely, in 1972  anatomical studies were undertaken and preliminary surgical trials in the human dorsal root entry zone (DREZ) to determine whether a destructive procedure at this level was feasible. Soon after, in 1974, Nashold and his group started to develop DREZ lesions using the RF thermocoagulation as the lesion maker in the substantia gelatinosa of the dorsal horn and later in the whole DREZ. This has been performed especially for pain caused by brachial plexus avulsion. Later on, DREZ procedures were performed by using a laser and an ultrasound probe for pain caused by brachial plexus avulsion.


This procedure consists of a longitudinal incision of the dorsolateral sulcus ventrolaterally at the entrance of the rootlets into the sulcus. Microbipolar coagulations are performed continuously inside the sulcus down to the apex of the dorsal horn and along all the spinal cord segments selected for surgery. The lesion, which penetrates the lateral part of the DREZ and the medial part of the tract of Lissauer (TL), extends down to the apex of the dorsal horn, which can be recognized by its brown-gray color. The average lesion is 2 to 3 mm deep and is made at a 35° angle medially and ventrally.
The procedure is presumed to preferentially destroy the nociceptive fibers grouped in the lateral bundle of the dorsal rootlets, as well as the excitatory medial part of the TL. The upper layers of the dorsal horn are also destroyed if microbipolar coagulations are made inside the dorsal horn . The upper layers of the dorsal horn are known to be the site of “hyperactive” neurons, especially in the cases with peripheral deafferentation (Fig.1). The procedure is presumed to at least partially preserve the inhibitory structures of the DREZ, (i.e., the lemniscal fibers reaching the dorsal column, as well as their recurrent collaterals to the dorsal horn and the substantia gelatinosa [SG] propriospinal interconnecting fibers running through the lateral part of the TL). This MDT was conceived in order to prevent the complete abolition of tactile and proprioceptive sensations and to avoid deafferentation phenomena.



FIGURE.1 Dorsal horn microelectrode recordings in man. The electrode was a floating tungsten microelectrode that was implanted intraoperatively free-hand under the operative microscope; it reached 5 mm in depth (in laminae IV–VI). The vertical bars are 50 μV, and the horizontal bars are 100 ms. Upper trace, normal activity. Recordings in a nondeafferented dorsal horn (spastic patient). Left, almost no spontaneous activity (3 spikes at random). Middle, spike burst discharges (arrows) evoked by regular light tactile stimulation of the corresponding dermatoma. Right, electrical stimulation of the corresponding peripheral nerve. Lower trace, deafferentation hyperactivity. Recordings in the L5 cord segment of a patient with pain caused by a traumatic section of the hemi-cauda equina from root L4 to S4. Left, spontaneous activity of the recorded unit: continuous, regular, high-frequency discharge. Middle, unit during light tactile stimulation of the L4–S1 dermatome (arrow). Right, during electrical stimulation of the tibial nerve (the arrows are two consecutive stimuli). Note the continuous regular discharges, which remain unaltered.


Working in the DREZ requires knowledge of the morphological anatomy of the dorsal roots corresponding to the spinal level. The axis of the dorsal horn in relation to the sagittal plan crossing the dorsolateral sulcus will condition the angulation of the DREZotomy. According to 82 measurements performed by Young, the mean DREZ angle is 30° at C6, 26° at T4, 37° at T12, and 36° at L3. The site and extent of the DREZ lesion will also be determined by the shape, width, and depth of the TL and dorsal horn (Fig.2).
Surgery is performed with the patient under general anesthesia, but with only an initial short-lasting muscle relaxant to allow intraoperative observation of motor responses to bipolar electrical stimulation of the nerve roots. Stimulated ventral roots have a motor threshold at least three times lower than the dorsal roots. Standard microsurgical techniques are used with 10× to 25× magnification.


The prone position with the head and neck flexed in the “concorde” position has the advantage of avoiding brain collapse caused by cerebral spinal fluid (CSF) depletion. The head is fixed with a three-pin head holder. The level of laminectomy is determined after identification of the prominent spinous process of C2 by palpation. A hemilaminectomy, generally from C4 to C7, with preservation of the spinous processes, allows sufficient exposure to the posterolateral aspect of the cervical spinal cord segments that correspond to the upper limb innervation, that is, the rootlets of C5 to T1 (T2).
After the dura and the arachnoid are opened longitudinally, the exposed roots and rootlets are dissected free by separation of the tiny arachnoid filaments that bind them to each other, to the arachnoid sheath, and to the spinal cord pia mater. The radicular vessels are preserved. Each ventral and dorsal root from C4 to T1 is electrically stimulated at the level of its corresponding foramen to precisely identify its muscular innervation and its functional value. Responses are in the diaphragm for C4 (the response is palpable below the lower ribs), in the shoulder abductors for C5, in the elbow flexors for C6, in the elbow and wrist extensors for C7, and in the muscles of the hand for C8 and T1.
Microsurgical lesions are performed at selected levels that correspond to the pain territory. The incision is made with a microknife. Then microcoagulations are made in a “chain” (i.e., dotted) manner. Each microcoagulation is performed by short-duration (a few seconds), low-intensity, bipolar electrocoagulation with a special sharp bipolar forceps. The depth and extent of the lesion depend on the degree of the desired therapeutic effect and the preoperative sensory status of the patient.



FIGURE.2 Variations of shape, width, and depth of the DREZ area, according to the spinal cord level (from left to right: cervical n° 7, thoracic n° 5, lumbar n° 4, sacral n° 3). Note how, at the thoracic level, Lissauer’s tract is narrow and the dorsal horn deep. Therefore, it is easy to understand that DREZ lesions at this level can be dangerous for the corticospinal tract and the dorsal column.


If the laxity of the root is sufficient, the sulcotomy is accomplished through an incision performed continuously in the dorsolateral sulcus, ventrolaterally along all of the rootlets of the targeted root. If this is not the case, a partial ventrolateral section is made successively on each rootlet of the root after the surgeon has isolated each one by separation of the tiny arachnoid membranes that hold them together.
For pain due to brachial plexus avulsion, dotted microcoagulations inside the dorsal horn (at least 3 mm in depth from the surface of the cord) are performed after incision of the dorsolateral sulcus. Sharp graduated bipolar forceps are used to make the microcoagulations at the level of the avulsed roots. Selective ventrolateral DREZ lesions are extended to the root remaining above and below. In brachial plexus avulsion, dissection of the spinal cord is sometimes difficult to achieve safely because of scar tissue adhering to the cord. Atrophy and/or gliotic changes at the level of the avulsed roots can make identification of the dorsolateral sulcus hazardous. In such cases, it is necessary to start from the roots remaining above and below. The presence of tiny radicular vessels that enter the cord may help determine the site of the sulcus. Yellow areas corresponding to old hemorrhages on the surface of the cord and/or microcavities in the depth of the sulcus and the dorsal horn provide some guidance for tracing the sulcomyelotomy. When the dorsolateral sulcus is difficult to find, intraoperative monitoring of the dorsal column somatosensory evoked potentials (SEPs) evoked by stimulation of the tibial nerve is especially helpful.


The patient is positioned prone on thoracic and iliac supports, and the head is placed 20 cm lower than the level of the surgical wound to minimize the intraoperative loss of CSF. The desired vertebral level is identified by palpation of the spinous processes or, if this is difficult, by a lateral x-ray study that includes the S1 vertebra. Interspinous levels identified by a needle can then be marked with methylene blue. A laminectomy—either bilateral or unilateral, according to pain topography—from T11 to L1 (or L2) is performed. The dura and arachnoid
are opened longitudinally and the filum terminale is isolated. Roots are then identified by electrical stimulation. The L1 and L2 roots are easily identified at their penetration into their respective dural sheaths. Stimulation of L2 produces a response of the iliopsoas and adductor muscles.
Identification of L3 to L5 is difficult for many reasons: (1) the exit through their respective dural sheaths is caudal to the exposure; (2) the dorsal rootlets enter the DREZ along an uninterrupted line; (3) the ventral roots are hidden in front of the dentate ligament; and (4) the motor responses in the leg to stimulation of the roots are difficult to observe intraoperatively because of the patient’s prone position. Stimulation of L3 produces a preferential response in the adductors and quadriceps, of L4 in quadriceps, and of L5 in the tibialis anterior muscle. Stimulation of the S1 dorsal root produces a motor response of the gastrocnemius- soleus group that can be confirmed later by repeatedly checking the Achilles ankle reflex before, during, and after MDT at this level.
Stimulation of the S2–S4 dorsal roots (or better, the corresponding spinal cord segments directly) can be assessed by recording the motor vesical or anal response by use of cystomanometry, rectomanometry, or electromyography of the anal sphincter (or by inserting a finger into the rectum). Because neurophysiological investigations are time-consuming to perform in the operating room, measurements at the conus medullaris can be sufficient in patients who already have severe preoperative impairment of their vesicoanal functions. These measurements, based on human postmortem anatomical studies, have shown that the landmark between the S1 and S2 segments is situated around 30 mm above the exit from the conus of the tiny coccygeal root.
At the lumbosacral level, MDT is difficult and possibly dangerous because of the rich vasculature of the conus. The posterolateral spinal artery courses along the posterolateral sulcus. Its diameter is between 0.1 and 0.5 mm, and it is fed by the posterior radicular arteries. It joins caudally with the descending anterior branch of the Adamkiewicz artery through the conus medullaris anastomotic loop of Lazorthes. If it is freed from the sulcus, this artery can be preserved.


Intraoperative monitoring of SEPs can be performed at the surface of the exposed spinal cord. Recordings of presynaptic potentials from the dorsal root and postsynaptic potentials from the dorsal horn can be useful for identification of the spinal cord segments. Potentials have a maximal amplitude in C6–C7 stimulation of the median nerve and the C8 segment for stimulation of the ulnar nerve. They have a maximum amplitude in the L5–S2 segments for stimulation of the tibial nerve, and in the S2–S4 segments for stimulation of the dorsal nerve of the penis or clitoris.



FIGURE.3  Effects of MDT on the evoked electrospinogram (EESG). Recordings from the surface of the dorsal column, medially to the DREZ at the C7 cervical (Ce) and the L5 lumbosacral (LS) segments, ipsilateral to the stimulation of the median and the tibial nerve, respectively, before (A) and after (B) MDT. The initial positive event P9 (for cervical) (P17 for lumbosacral) corresponds to the far-field compound potential originating in the proximal part of the brachial (lumbosacral) plexus. The small and sharp negative peaks N11 (N21) correspond to near-field presynaptic successive axonal events, probably generated in the proximal portion of the dorsal root, the dorsal funiculus, and the large-diameter afferent collaterals to the dorsal horn. After MDT, all of these presynaptic potentials remain unchanged. The larger slow negative wave N13 (N24) corresponds to the postsynaptic activation of the dorsal horn by group I and II peripheral afferent fibers of the median (tibial) nerves. They are diminished after MDT (in the order of two thirds). The later negative slow wave N2 (just visible in the cervical recording) corresponds to postsynaptic dorsal horn activity consecutive to the activation of group II and III afferent fibers. N2 is suppressed after MDT.


Recordings of surface spinal cord SEPs can also be helpful in monitoring the surgical lesion itself. Dorsal column potentials can be monitored to check the integrity of the ascending dorsal column fibers, especially when the dorsolateral sulcus is not clearly marked (as is common in brachial root avulsion). The dorsal horn potentials can be monitored to follow the extent of MDT, particularly when good sensory functions are present before surgery.


Unitary spikes generated in the dorsal horn neurons are interesting to record during DREZotomy to indicate abnormal activities, to help identify the surgical target, and to better understand the electrophysiological mechanisms underlying painful phenomena. Toward this goal, one group has developed special, simplified floating microelectrodes. At the beginning, these electrodes were based on the design by Merril and Ainsworth, and later they were developed into an original design (i.e., a double microelectrode with an enhanced ability to distinguish spikes from artifacts). In this way, they conducted recordings in 25 patients. To learn about specific patterns recorded from deafferented neurons, more patients must be studied. The group has performed microdialysis studies in the dorsal horn of patients undergoing DREZotomy. The aim of the work was to measure concentrations of some of the main neurotransmitters hypothesized from the animal experiments to be present in the human dorsal horn. The microprobe has an apical 4-mm-long tubular
membrane [diameter: 0.216 mm, Cuprophane (HOSPAL Industrie, Meyzieu, France), cutoff 6000 Da]. The probe is perfused at 2 μl/min with a Ringer solution. Dialysate fractions are collected from the extracellular fluid every 5 min for about 1 hr. All the samples are frozen for later analysis [high performance liquid chromatography (HPLC) with fluometric detection]. At the present time they have made the technique feasible for identification and dosages of the following substances: glutamate, aspartate, GABA, glycine, taurine, serine, and threonine. The preliminary results indicate some differences between painful and nonpainful states. Further studies are needed before giving conclusions.


In 1976 Nashold and his group published data on a method using RF thermocoagulation to destroy hyperactive neurons in the substantia gelatinosa and in 1979 in the whole DREZ region. In 1981 the technique was modified to produce less extensive lesioning so that the risk of encroachment into the neighboring corticospinal tract and dorsal column would be minimized. With the modified technique, the lesion is made with a 0.5 mm insulated stainless steel electrode with a tapered noninsulated 2 mm tip, designed and manufactured by Radionics Inc. (Burlington, MA).
For treatment of pain after brachial plexus avulsion, the electrode penetrates the dorsolateral sulcus to a depth of 2 mm at an angle of 25–45° in the lateral– medial direction. A series of RF coagulations are made under a current of 35–40 mA (not over 75°C) for 10–15 s. The RF lesions are spaced at 2–3 mm intervals along the longitudinal extent of the dorsolateral sulcus. The lesion observed under magnification is seen as a circular whitened area that extends 1–2 mm beyond the tip of the electrode.
In a recent publication, Nashold emphasizes the importance of obtaining impedance measurements from tissue during surgery. Before and after each lesion is made, the impedance has to be measured. It is usually less than 1200 Ω in a damaged spinal cord. The authors state that as the transition from injured parenchyma into more normal tissue is made, impedance readings should increase and eventually reach normal levels of 1500 Ω. The authors use these numbers as a guide to stop the lesion making at the desired end.


Levy et al. in 1983 and Powers et al. in 1984  advocated CO2 and argon lasers, respectively, as lesion makers. According to Levy et al.’s description, the pulse duration of the CO2 laser is 0.1 sec and the power is adjusted to about 20 W, so that one or two single pulses create a 2 mm depression at a 45° angle in the DREZ. The lesions are probed with a microinstrument marked at 1 mm increments to ensure that the depth of the lesions (1–2 mm) is adequate. Intraoperative observations in humans and experimental studies comparing DREZ lesions performed with the RF thermocoagulation to those made with various laser beams found that the laser lesions were generally more circumscribed and less variable. Walker et al., on the other hand, reported on the danger of creating extensive damage and syrinx cavities with the laser (CO2). In a well-documented study evaluating the effects of DREZ lesions with RF or CO2 on the dog spinal cord, Young found that the size and extent of the lesion related primarily to the magnitude of power used to make the lesion. They showed that by using any of the three techniques, the lesions could be successfully localized to the DREZ (including the layers I–VI of the dorsal horn) and the dorsal column and the corticospinal tract spared. The main difference was that with the laser, the lesion was shaped like the letter “V”, with the maximum width at the surface, whereas with RF it tended to be more spherical.The same glial reactions were observed using both methods in chronic animal models.
Young, in his series of patients, made a comparative analysis of RF and CO2-laser procedures. With RF, 39 of the 58 patients (67%) reported good results (pain regressed by 50% or more) and with the CO2 laser, 9 out of the 20 patients (45%) reported good results. Postoperative complications with RF were noted in 26%, and with CO2 laser in 15%.


This procedure was developed by Kandel and Dreval in Moscow. It has been mostly used for pain caused by brachial plexus avulsion. According to the description given by Dreval, the technique consists of a continuous longitudinal opening of the dorsolateral sulcus at the level of the avulsed roots to the depth of the microcavities and the changed spongy cord tissue. At the same time, ultrasonic destruction of the pathological tissues is done. The lesion is strictly in the projection of the dorsolateral sulcus at an angle of 25° medially and ventrally. The depth of the microcavities is the main criterion of the depth of the lesioning. After ultrasonic DREZ sulcomyelotomy, the grey color of the dorsal horn is well seen in the depth of the opened dorsolateral sulcus. The vessels crossing the sulcus are kept intact. The ultrasonic lesions are produced at a working frequency of 44 kHz, and the amplitude of ultrasonic oscillation is 15–50 μm. The lesions are placed in a “chain” manner along the sulcus.


Indications are as follows:
1. Cancer pain that is limited in extent (such as in Pancoast-Tobias syndrome).
2. Persistent neurogenic pain that is due to:
A) Brachial plexus injuries, especially those with avulsion.
B) Spinal cord lesions, especially for pain corresponding to segmental lesions. Pain below the lesion is not favorably influenced. Segmental pain caused by lesions in the conus medullaris and the cauda equina is significantly relieved. Pain due to cauda equina lesions can also be indications.
C) Peripheral nerve injuries, amputation, and herpes zoster, when the predominant component of pain is of the paroxysmal type and/or corresponds to provoked allodynia hyperalgesia.
3. Disabling hyperspasticity with pain.
Surgery in the DREZ must be considered alongside other methods belonging to the armamentarium of pain surgery. Figure.4 summarizes present
process of decision making for neuropathic pain.



FIGURE.4 Decision making for neuropathic pain, originating from the following: upper left, peripheral nerves, plexus, roots distal to ganglion lesions; upper right, roots central to ganglion lesions; lower right, incomplete and complete spinal cord lesions; lower left, treatment for the segmental and the infralesional components of the pain are different.


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