Clinical review of nucleus caudalis dorsal root entry zone lesions for facial pain

Twenty-seven patients with intractable facial pain underwent dorsal root entry zone thermocoagulation lesion of the nucleus caudalis of the spinal trigeminal nucleus. Retrospective review revealed a success rate of 85% in the immediate postoperative period declining to 52% on subsequent follow-up. The best results were in the subgroup of patients with postherpetic neuralgia, of which 67% achieved definite relief. There tended to be some correlation of satisfactory results and pain quality as well as extent of pain along trigeminal territory. The operative morbidity was low although most patients were observed to have a mild transient ipsilateral dysmetria.     

Anatomic examination of human dorsal root entry zone lesions

The anatomic delineation of radiofrequency dorsal root entry zone lesions using the Nashold thermocouple electrode is presented. The sharply delineated lesions involve a major portion of the dorsal horn of the spinal cord including Rexed's lamina V and part of VI. The extent of these lesions is appropriate, based on the currently understood mechanisms of spinal generators of chronic deafferentation pain.     

Pain control with laser-produced dorsal root entry zone lesions

Pain relief was evaluated in 40 patients with various types of deafferentation pain that were treated with dorsal root entry zone (DREZ) lesions produced with microsurgical lasers. Good long-term pain relief was evident in some paraplegics and in all patients with brachial plexus avulsion. Several other small subgroups of patients benefited from laser DREZ lesions as well. Pain associated with arachnoiditis and peripheral nerve injury or neuropathy did not respond to laser DREZ lesioning. Based upon the smaller lesion dimensions produced with the lasers, it is proposed that interruption of impulses in the tract of Lissauer may be a mechanism of pain control in patients that responded to laser DREZ lesions.     

Successful treatment of phantom pain with dorsal root entry zone coagulation

We studied 22 patients with amputation due to trauma, gangrene, or cancer. All developed postamputation pain, underwent a dorsal root entry zone (DREZ) procedure, and were followed from 6 months to 4 years after surgery. Overall, only 8 (36%) of these 22 patients had pain relief. However, good results were obtained in 6 (67%) of 9 patients with phantom pain alone, and in 5 (83%) of 6 patients with traumatic amputations associated with root avulsion. Poor results were obtained in patients with both phantom and stump pain, or stump pain alone. The DREZ procedure has a well-defined, but limited role in the treatment of postamputation pain.     

Involuntary movements of the lower extremity following dorsal root entry zone lesions in a man treated for phantom limb pain

A patient developed continuous patterned involuntary movements of abduction-adduction, flexion-extension of his right lower extremity following surgical placement of spinal dorsal root entry zone lesions for the treatment of phantom limb pain. The stereotype movements were monitored by video and electromyographic recording of quadriceps femoris and hamstring muscles. Administration of para-chlorophenylbutyric acid (baclofen) dramatically stopped the involuntary movements and electromyographic silence ensued. Voluntary muscle movements were preserved. The theoretical implications of this unique movement disorder and central patterning of motor activity within the spinal cord are discussed.     

Neurosurgical technique of the dorsal root entry zone operation

The dorsal root entry zone operation was introduced in 1976 to relieve the pain of brachial plexus avulsion. Since then it has been applied to pain treatment in paraplegia, postherpetic pain, phantom limb pain and other types of of deafferentation pain. Over 400 operations have been done at the Duke University Medical Center with overall good results in 60% of pain patients.     

Dorsal root entry zone lesions for conus medullaris root avulsions

We have found dorsal root entry zone (DREZ) lesions to be an effective treatment of chronic deafferentation pain in patients who have had avulsions of the dorsal rootlets from the spinal cord. Eight patients were operated in whom chronic pain of the lower extremity resulted from dorsal root avulsions from the conus medullaris. In 7 of the 8 patients, the mechanism of injury was a motor vehicle accident; all 7 sustained severe pelvic trauma. Seven of the 8 patients remained pain-free, off all narcotics, with an average follow-up of 33 months. All patients had DREZ lesions of the conus performed by radiofrequency techniques.     

Lesions of spinal and trigeminal dorsal root entry zone for deafferentation pain. Experience of 35 cases

Spinal and trigeminal dorsal root entry zone destruction (DREZ-tomy) was performed on 35 patients with deafferentation pain of various types. Overall, satisfactory pain relief was obtained in 65.5% of spinal DREZ-tomy cases in the follow-up observation. The result in the brachial plexus avulsion group was the best (82.4% improved), followed by the limb pain group without root avulsion (50.0%), but the truncal or visceral pain group showed the worst result (33.3%). Two patients with postherpetic trigeminal neuralgia were completely relieved of pain in the average follow-up period of 32 months, while in 2 patients with postrhizotomy facial pain, pain recurred 4 months after the operation in 1, and, in the other, pain in the medial part of the face remained unchanged. Complications were seen in about 60% of the patients, which were, however, all mild, except for 2 cases of death due to gastrointestinal disease.     

Dorsal root entry zone lesions in the treatment of pain following brachial plexus avulsion, spinal cord injury and herpes zoster

This paper details the long-term results in patients treated with dorsal root entry zone (DREZ) lesions for the treatment of pain following brachial plexus avulsion, spinal cord injury, and herpes zoster. With our current operative technique, 82% of patients with brachial plexus avulsion injuries were afforded long-term pain relief. Patients with pain confined to dermatomes just below the level of spinal injury also did well with DREZ lesions, although the results were less good in patients with diffuse pain or with sacral pain. The postoperative results in patients with postherpetic pain were disappointing.     

Dorsal root entry zone coagulation for intractable sciatica

Chronic back and leg pain which is unresponsive to medical and/or surgical treatment is a common and difficult neurosurgical problem. Twelve patients with this condition underwent dorsal root entry zone coagulation of that region of the conus medullaris which correlated with the pain. Only 2 patients had a favorable result. The implications of this finding are discussed.     

Human dorsal root ganglion neurons from embryonic donors extend axons into the host rat spinal cord along laminin-rich peripheral surroundings of the dorsal root transitional zone

Following dorsal root crush, the lesioned axons regenerate in the peripheral compartment of the dorsal root, but stop at the boundary between the peripheral and the central nervous system, the dorsal root transitional zone. We have previously shown that fibres from human fetal dorsal root ganglia grafted to adult rat hosts are able to grow into the spinal cord, but were not able to specify the route taken by the ingrowing fibres. In this study we have challenged the dorsal root transitional zone astrocyte boundary with human dorsal root ganglion transplants from 5–8-week-old embryos. By tracing immunolabelled human fibres in serial sections, we found that fibres consistently grow around the dorsal root transitional zone astrocytes in laminin-rich peripheral surroundings, and extend into the host rat spinal cord along blood vessels, either into deep or superficial laminae of the dorsal horn, or into the dorsal funiculus. Human fibres that did not have access to blood vessels grew on the spinal cord surface. These findings indicate, that in spite of a substantial growth capacity by axons from human embryonic dorsal root ganglion cells as well as their tolerance to non-permissive factors in the mature mammalian CNS, these axons are still sensitive to the repellent effects of astrocytes of the mature dorsal root transitional zone. Furthermore, this axonal ingrowth is consistently associated with laminin-expressing structures until the axons reach the host spinal cord.     

Experimental analysis of the extension of the dorsal marginal zone in Pleurodeles waltl gastrulae

The capacity for extension of the dorsal marginal zone (DMZ) in Pleurodeles waltl gastrulae was studied by scanning electron microscopy and grafting experiments. At the onset of gastrulation, the cells of the animal pole (AP) undergo important changes in shape and form a single layer. As gastrulation proceeds, the arrangement of cells also changes in the noninvoluted DMZ: radial intercalation leads to a single layer of cells. Grafting experiments involving either AP or DMZ explants were performed using a cell lineage tracer. When rotated 90 degrees or 180 degrees, grafted DMZ explants were able to involute normally and there was extension according to the animal-vegetal axis of the host. In contrast, neither single nor bilayered explants from AP involutes completely, and neither extends when grafted in place of the DMZ. Furthermore, when inside of the host, these AP grafts curl up and inhibit the closure of the blastopore. Once transplanted to the AP region, the DMZ showed no obvious autonomous extension. DMZs cultured in vitro showed little extension and this only from the late gastrula stage onward. Removal of blastocoel roof blocked involution to a varied extent, depending on the developmental stage of the embryos. From these results, it is argued that differences could well exist in the mechanism of gastrulation between anuran and urodele embryos. That migrating mesodermal cells play a major role in urodele gastrulation is discussed.     

Safety of early pain relief for acute abdominal pain.

OBJECTIVES--(a) to determine the efficacy of papaveretum in treating pain when administered early to patients presenting with acute abdominal pain and (b) to assess its effect on subsequent diagnosis and management. DESIGN--Prospective, randomised, placebo controlled study. SETTING--Walsgrave Hospital, Coventry. SUBJECTS--100 consecutive patients with clinically significant abdominal pain who were admitted as emergencies to a surgical firm. INTERVENTIONS--Intramuscular injection of up to 20 mg papaveretum or an equivalent volume of saline. OUTCOME MEASURES--Pain and tenderness scores, assessment of patient comfort, accuracy of diagnosis, and management decisions. RESULTS--Median pain and tenderness scores were lower after papaveretum (pain score 8.3 in control group and 3.1 in treatment group, p < 0.0001; tenderness score 8.1 in control group and 5.1 in treatment group, p < 0.0001). Forty eight patients were deemed to be comfortable after papaveretum compared with nine after saline. Incorrect diagnoses and management decisions applied to two patients after papaveretum compared with nine patients after saline. CONCLUSION--Early administration of opiate analgesia to patients with acute abdominal pain can greatly reduce their pain. This does not interfere with diagnosis, which may even be facilitated despite a reduction in the severity of physical signs. These patients should not be denied effective treatment.     

HSV-mediated expression of interleukin-4 in dorsal root ganglion neurons reduces neuropathic pain

Background

Triptans, 5-HT_1B/ID agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca²⁺ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca²⁺ channels are not yet documented.

Results

In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca²⁺ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba²⁺ currents (I_Ba) passing through Ca²⁺ channels. Zolmitriptan (0.1–100 μM) reduced the size of I_Ba in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT_1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca²⁺ channel blockers inhibited the inhibitory action of zolmitriptan on I_Ba, compared to N- and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT_1B/1D receptor linked to G_i/o pathway.

Conclusion

It is concluded that this zolmitriptan inhibition of HVA Ca²⁺ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.     

TRP channels: targets for the relief of pain

Patients with inflammatory or neuropathic pain experience hypersensitivity to mechanical, thermal and/or chemical stimuli. Given the diverse etiologies and molecular mechanisms of these pain syndromes, an approach to developing successful therapies may be to target ion channels that contribute to the detection of thermal, mechanical and chemical stimuli and promote the sensitization and activation of nociceptors. Transient Receptor Potential (TRP) channels have emerged as a family of evolutionarily conserved ligand-gated ion channels that contribute to the detection of physical stimuli. Six TRPs (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8 and TRPA1) have been shown to be expressed in primary afferent nociceptors, pain sensing neurons, where they act as transducers for thermal, chemical and mechanical stimuli. This short review focuses on their contribution to pain hypersensitivity associated with peripheral inflammatory and neuropathic pain states.     

Percutaneous radiofrequency lesions adjacent to the dorsal root ganglion alleviate spasticity and pain in children with cerebral palsy: pilot study in 17 patients

Background  

Cerebral palsy (CP) may cause severe spasticity, requiring neurosurgical procedures. The most common neurosurgical procedures are continuous infusion of intrathecal baclofen and selective dorsal rhizotomy. Both are invasive and complex procedures. We hypothesized that a percutaneous radiofrequency lesion of the dorsal root ganglion (RF-DRG) could be a simple and safe alternative treatment. We undertook a pilot study to test this hypothesis.     

Experimental colitis modulates the functional properties of NMDA receptors in dorsal root ganglia neurons

N-methyl-D-aspartate (NMDA) receptors (NMDARs) on spinal afferent neurons regulate the peripheral and central release of neuropeptides involved in the development of hyperalgesia. We examined the effect of experimental colitis on the molecular and functional properties of NMDARs on these neurons. Lumbosacral dorsal root ganglia (DRG) were collected from adult rats 5 days after the induction of colitis for whole cell patch-clamp recording, Western blot analysis, and quantitative RT-PCR. Compared with neurons from control rats, those taken from animals with colitis had a threefold higher density of NMDA currents in both retrograde-labeled, colon-specific, and unlabeled DRG neurons. Increased current densities were not observed in DRG neurons taken from thoracic spinal levels. There was no significant change in NMDA or glycine affinity or in voltage-dependent Mg2+ inhibition; however, there was a 10-fold decrease in sensitivity to the NR2B subunit-selective antagonist ifenprodil. Quantitative RT-PCR and Western blot analysis indicated a 28% increase in the expression of NR2B with little or no change in the other three NR2 subunits. The addition of the Src family tyrosine kinase inhibitor PP2 (10 microM) decreased NMDAR currents in neurons from colitis but not control rats. Conversely, pretreatment of DRG neurons from control animals with 100 microM sodium orthovanadate increased NMDAR currents and decreased ifenprodil sensitivity to levels similar to those observed in neurons from animals with colitis. In conclusion, colonic inflammation upregulates the activity of NMDARs in all DRG neurons within ganglia innervating this tissue through mechanisms involving increased expression and persistent tyrosine phosphorylation.     

Routing of transported materials in the dorsal root and nerve fiber branches of the dorsal root ganglion

After injection of the L7 dorsal root ganglion with ³H-leucine, fast axoplasmic transport carries some 3–5 × more labeled materials down the sensory fibers branches entering the sciatic nerve as compared to the dorsal root fiber branches of the neurons. Freeze-substitution preparations taken from the two sides of the lumbar seventh dorsal root ganglia of cats and monkeys showed little difference in the histograms of nerve fiber diameters of the sensory nerve fiber branch of these neurons as compared to the dorsal root fiber branches. A similar density of microtubules and of neurofilaments in the dorsal root and sensory nerve fiber branches over a wide range of fiber diameters was found in electron micrograph preparations. In the absence of an anatomical difference in the fibers to account for the asymmetrical outflow, a functional explanation based on the transport filament model was advanced.