Chronic precentral stimulation in trigeminal neuropathic pain

Summary The results of Deep Brain Stimulation in deafferentation pain syndromes, in particular in thalamic pain, indicate that excellent long-term pain relief can hardly ever be achieved. We report 7 cases using Motor-Cortex-Stimulation for treating severe trigeminal neuropathic pain syndromes, i.e., dysaesthesia, anaesthesia dolorosa and postherpetic neuralgia. The first implantation of the stimulation device for precentral cerebral stimulation was performed in June 1993, the last in September 1995. In all but one case the impulse-generator was implanted after a successful period of test stimulation. Successful means a pain reduction of more than 50% as assessed with a Visual Analogue Scale. Excluding one case, in whom a prolonged focal seizure resulting in a postictal speech arrest occurred during test stimulation, there have been no operative complications and the postoperative course was uneventful. In all the other patients the pain inhibition appeared below the threshold for producting motor effects. Initially these patients reported a good to excellent pain relief. In three of 6 patients a good to excellent pain control was maintained for a follow-up period of 5 months to 2 years. In the remaining three patients the positive effect decreased over several months.     

Bilateral cortical stimulation for deafferentation pain after spinal cord injury. Case report

The relief of intractable pain after spinal cord injury (SCI) is very difficult to obtain, even with dorsal root entry zone lesioning, spinal cord stimulation, and thalamic stimulation. Using bilateral motor cortex stimulation (MCS) the authors successfully treated a woman who experienced deafferentation pain 4 years after sustaining an SCI. To the authors' knowledge, this is the first report of bilateral MCS for pain relief after SCI. The success they achieved using this method indicates that MCS could be a new treatment option for deafferentation pain following SCI.     

Brain stimulation

Electrical stimulation in the PAG has been shown to elicit profound analgesia in experimental animals that is at least in part due to the release of endogenous opioid substances. Electrical stimulation in the thalamic nuclei VPL and VPM inhibits the activation of spinal dorsal horn neurons by noxious stimuli. Acute electrical stimulation in these two targets relieves chronic pain in about 80% of patients. Chronic electrical stimulation by permanently implanted electrodes relieves pain in about 70% of patients with pain of peripheral or nociceptive origin but in only about 50% of patients with central pain resulting from deafferentation. Stimulating electrodes are implanted stereotactically by a burr hole under local anesthesia. Transient complications occur in 15% to 25% of patients and include infections, malfunctions of the stimulating hardware, pain at the implant sites, and mild temporary neurologic deficits. Permanent complications, including hemiparesis, intracranial hemorrhage, and death, occur in 1% to 2% of patients. Brain stimulation is recommended for the treatment of chronic pain in patients in whom other forms of treatment have failed. The technique is reasonably safe and provides pain relief for a group of patients who have exhausted all other therapeutic modalities. Unfortunately, not all patients receive effective pain relief with brain stimulation. Other stimulation targets such as the K-F nucleus in the parabrachial region of the brain stem are currently being explored in an attempt to provide pain relief to a greater proportion of patients. In addition, improvements in stimulation hardware have made the technique easier and more effective.     

Phantom limb pain: cortical plasticity and novel therapeutic approaches

Phantom limb pain is still a very frequent consequence of peripheral deafferentation or amputation of a limb. Recent findings from animal and neuroimaging studies suggest that phantom limb pain might be a central phenomenon, related to changes in the cortical, thalamic and spinal representation of the painful limb, and might be a type of somatosensory pain memory. Based on these assumptions, new treatment approaches focus on sensory discrimination training or motor cortex stimulation in an effort to influence cortical reorganization. Prevention of perpetuation of a somatosensory pain memory might also be possible through pharmacological agents such as N-methyl-D-aspartate antagonists and gamma-aminobutyric acid agonists, substances that have been shown to influence and prevent cortical reorganization.     

Treatment of central and neuropathic facial pain by chronic stimulation of the motor cortex: value of neuronavigation guidance systems for the localization of the motor cortex

Thirty two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27. 3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (8 new patients and 5 reinterventions) were operated by a technique including localization by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and nine of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the 3 patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zoster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localization and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.     

Recording of corticospinal evoked potential for optimum placement of motor cortex stimulation electrodes in the treatment of post-stroke pain

The corticospinal motor evoked potential (MEP) evoked by motor cortex stimulation was investigated as an intraoperative index for the placement of stimulation electrodes in the epidural space over the motor cortex for the treatment of post-stroke pain. A grid of plate electrodes was placed in the epidural space to cover the motor cortex, sensory cortex, and premotor cortex employing a magnetic resonance imaging-guided neuronavigation system in two patients with severe post-stroke pain in the right extremities, a 66-year-old man with dysesthesia manifesting as burning and aching sensation, and a 67-year-old woman with dysesthesia manifesting as pricking sensation. The D-wave of the corticospinal MEP was recorded with a flexible wire electrode placed in the epidural space of the spinal cord during anodal monopolar stimulation of each plate electrode under general anesthesia. The grid electrode was fixed in position with dural sutures and the craniotomy closed. The effect of pain reduction induced by anodal monopolar stimulation of the same plate electrodes was examined using the visual analogue scale (VAS) on a separate day in the awake state without anesthesia. Comparison of the percentage VAS reduction and the recorded amplitude of the D-wave employing the same stimulation electrode revealed significant correlations in Case 1 (r = 0.828, p < 0.01) and Case 2 (r = 0.807, p < 0.01). The grid electrode was then replaced with two RESUME electrodes over the hand and foot areas, and the optimum positions were identified by D-wave recording before electrode fixation. Both patients reported satisfactory pain alleviation with lower stimulation voltages than usually required for patients with similar symptoms. These results indicate the potential of D-wave recording as an intraoperative indicator for the placement of stimulating electrodes over the motor cortex for pain relief.     

Augmentative treatment of chronic deafferentation pain syndromes after peripheral nerve lesions.

Deafferentation pain syndromes developing after peripheral nerve lesions are difficult to treat. According to the follow-up (mean: 39.5 months) of 6 patients suffering from causalgic pain we will present our method of augmentative therapy in chronic neuropathic pain caused by peripheral nerve lesions, i.e., peripheral nerve stimulation (PNS), spinal cord stimulation (SCS) and chronic intrathecal opioid infusion. None of the patients showed intraoperative or follow-up complications. Evaluated by visual analogue scales all patients reported a good to excellent pain relief (75-100%). (1) Regarding the favourable long-term results of PNS, this method should be considered in cases of mononeuropathic pain syndromes. (2) Neuropathic pain syndromes which are not assignable to a singular nerve lesion, can often be managed effectively by SCS. (3) In contrast to the widespread opinion, deafferentation pain syndromes of central or peripheral origin can be treated satisfactorily by intrathecal opiate administration.     

Chronic sciatalgia caused by sensitive deafferentiation following surgery for lumbar disk hernia: clinical and therapeutic aspects. Apropos of 110 patients]

Sensitive deafferentation is a well recognized entity which has changed the therapeutic approach of some kinds of chronic post operative sciatalgia. It mainly occurs related with a long story of radicular pain and the responsibility of so-called epidural fibrosis has to be discussed. The case records of 110 consecutive patients with deafferentation sciatalgia were reviewed and the clinical data precised: chronic and lasting burning pain with acute nightly paroxysms and sensitive alterations at objective examination. Neuroradiological explorations eliminated the possibility of recurrent disc herniation and neurophysiological tests assessed the chronic radicular suffering and the degree of lemniscal degeneration. After medical treatment (analgesic drugs with central tropism), a strict clinical assessment of pain intensity allowed optimal choice of the technique of neurostimulation: transcutaneous electrical stimulation (51 patients) and/or spinal cord stimulation (59 patients). The efficacy of transcutaneous stimulation (40 excellent and good results) was most often related to its continuous utilisation with a short post-effect. Its side-effects and the frequency of multiradicular involvement lead to spinal cord stimulation. With a mean follow-up period of 37 months, the pain relief was considered as excellent in 51.5%, good in 38% and poor in 8.5% of the patients. One patient had a negative test and was not definitively implanted. Another case failed to respond to stimulation. The clinical and technical complication of the method are reported.     

Neural mechanisms underlying deafferentation pain: a hypothesis from a neuroimaging perspective

Deafferentation pain following nerve injury annoys patients, and its management is a challenge in clinical practice. Although the mechanisms underlying deafferentation pain remain poorly understood, progress in the development of multidimensional neuroimaging techniques is casting some light on these issues. Deafferentation pain likely results from reorganization of the nervous system after nerve injury via processes that interact with the substrates for pain perception (the pain matrix). Therapeutic effects of motor cortex stimulation on deafferentation pain suggest that the core mechanisms underlying deafferentation pain also interact with the motor system. Therefore, simultaneous neuroimaging and brain stimulation, an emerging neuroimaging technique, was developed to investigate complicated interactions among motor, somatosensory, and pain systems. In healthy participants, parts of the pain matrix (the anterior cingulate cortex, parietal operculum, and thalamus) show activity during both somatosensory stimulation and brain stimulation to the motor cortex. This finding indicates that motor, somatosensory, and pain systems communicate among each other via the neural network. A better understanding of the plastic mechanisms influencing such cross-talk among these systems will help develop therapeutic interventions using brain stimulation and neurofeedback.     

Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature

Since the senior author's (J.E.A.) first report in 1972 of the use of deep brain stimulation (DBS) to control chronic pain, electrodes for DBS have been implanted in 141 patients. Of reported series, this one has the largest number of patients and the longest period of follow-up. The mean age of patients in this study was 51.2 years. The mean length of follow-up was 80 months. Patients had experienced pain for a mean period of 65 months before DBS was attempted; all patients had exhausted other medical and surgical therapies. For the purposes of this study, pain states were characterized as being either nociceptive or deafferentation in nature. Nociceptive pain was treated primarily by stimulation of the periaqueductal or periventricular gray, and deafferentation pain was treated primarily by stimulation of the sensory thalamus. Eighty-four patients were treated for deafferentation pain, which included the thalamic pain syndrome (25 cases), peripheral neuropathic pain (16 cases), anesthesia dolorosa (12 cases), paraplegia pain (11 cases), postcordotomy dyesthesia (5 cases), phantom limb pain (5 cases), thoracic neuralgia (4 cases), and miscellaneous pain states (6 cases). We treated 57 patients with nociceptive pain states, 51 for low back and skeletal pain and 6 for pain from the invasion of cancer. Initial relief of pain was obtained by 83 patients (59%). After the mean follow-up period of 80 months, 42 patients (31%) continued to obtain significant pain relief with DBS. Some pain states, particularly anesthesia dolorosa and paraplegia pain, did not seem to respond to DBS. Major complications of therapy included wound infection (12%) and intracranial hemorrhage (3.5%); there was one death in the series (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral nerve stimulation in the treatment of intractable pain.

Peripheral nerve stimulating devices were implanted for pain control in 33 patients with a variety of disabling chronic pain conditions, which had persisted despite usual medical and surgical therapy. The implants were placed on major nerves innervating the area of the patient's pain. Records were obtained of each patient's stated relief from pain produced by nerve stimulation, along with assessments of narcotic withdrawal, ability to return to work, sleep pattern, and relief from depression. Based on these five criteria 17 patients were judged to be treatment failures, while eight patients had excellent results, and seven had intermediate results. Twelve of the failures were in patients with either low back pain with sciatica, or pain from metastatic disease. The most dramatic successes occurred in patients with peripheral nerve trauma. The incidence of complications has been low, and two patients have used the stimulator for 5 years without adverse effects. Techniques of peripheral stimulator implantation, possible mechanisms of action, and conclusions regarding peripheral nerve stimulation in the treatment of chronic pain are discussed.     

Motor cortex stimulation for post-stroke pain using neuronavigation and evoked potentials: report of 3 cases

Although motor cortex stimulation (MCS) has been accepted as an effective therapeutic option for central pain, the efficacy of MCS widely varies among previous reports. In this report, we describe our recent trial for successful MCS in 3 patients with central pain due to cerebral stroke. Medical treatments were transiently effective, but gradually became ineffective in all of the cases. During surgery, the appropriate cortical target was determined by using neuronavigation, somatosensory evoked potential (SEP), and motor evoked potential (MEP). A flat, four-plate electrode was positioned on the dura mater parallel to the motor cortex. After surgery, pain almost resolved in 2 of 3 patients and markedly improved in another. The pain relief depended on their motor function. These findings strongly suggest that both patient selection and intraoperative monitoring for targeting the motor cortex are quite important for successful MCS, although further studies were essential.     

Efficacy of motor cortex stimulation in the treatment of neuropathic pain: a randomized double-blind trial

OBJECT: In this study the authors used a double-blind protocol to assess the efficacy of motor cortex stimulation (MCS) for treating neuropathic pain. METHODS: Eleven patients with unilateral neuropathic pain (visual analog scale [VAS] score 8-10) of different origins and topography were selected for MCS. A 20-contact grid was implanted through a craniotomy centered over the motor cortex contralateral to the painful area. The motor cortex strip was identified using neuroimages, somatosensory evoked potentials, acute electrical stimulation, and corticocortical evoked potentials. Subacute therapeutic stimulation trials allowed the authors to determine the most efficient pair of contacts to use for long-term MCS. The grid was replaced with a 4-contact electrode connected to an internalized stimulator. Bipolar stimulation at a 40-Hz frequency, 90-micro sec pulse width, amplitude 2-7 V, and 1 hour in "ON" and 4 hours in "OFF" mode was used. Pain was evaluated using the VAS, Bourhis, and McGill pain scales applied each month for 1 year. At Day 60 or 90, the stimulators were turned to OFF mode for 30 days in a randomized, double-blind fashion. The statistical tool used was the Wilcoxon test. RESULTS: Three patients did not report improvement in the subacute trial and were excluded from long-term MCS; the remaining patients underwent long-term stimulation. Significant improvement of pain was induced by MCS (p < 0.01); this persisted during the follow-up period. Turning stimulation to OFF mode increased pain significantly (p < 0.05). Improvement at 1 year was >or= 40% (40-86%) in all cases. CONCLUSIONS: Motor cortex stimulation is an efficient treatment for neuropathic pain, according to an evaluation facilitated by a double-blind maneuver. Subacute stimulation trials are recommended to determine the optimum motor cortex area to be stimulated and to identify nonresponders.     

Microsurgical junctional DREZ coagulation for treatment of deafferentation pain syndromes

BACKGROUND: In the treatment of intractable deafferentation pain, different procedures in the DREZ have proved most effective. For most of the spot-like techniques special equipment is mandatory. In this study the technique and the results of junctional DREZ coagulation for treatment of different pain syndromes with the help of bipolar forceps is presented. METHODS: In 40 patients with intractable deafferentation pain syndromes a junctional DREZ coagulation lesion along the entire dorsolateral fissure of the involved spinal cord segments was made using bipolar forceps. Etiologies of the pain included avulsion of the brachial plexus (21 cases), postherpetic pain (4 cases), phantom pain (3 cases), peripheral nerve injury (3 cases), reflex sympathetic dystrophy (2 cases), spinal cord transsection (1 case), and syringomyelia (6 cases). RESULTS: Of 21 patients who underwent junctional DREZ surgery for pain because of brachial plexus avulsion 10 (47.6%) had complete, 7 (33.3%) excellent, 3 (14.3%) good, and 1 (4.7%) fair pain relief (follow-up 20 to 120 months). In the group of 19 patients (follow-up 6 to 84 months) with pain syndromes other than postavulsion pain we achieved excellent results in 10 cases (52.6%), good in 8 (42.1%) and no pain relief in 1 case (5.3%). Transient sensory neurological disturbances lasting up to 8 weeks were observed in 6 (15%) cases; permanent sensory and motor deficit in 1 (2.5%) case. CONCLUSIONS: Clinical results of junctional coagulation DREZ lesion for the treatment of deafferentation pain syndromes are promising. There is no need for special equipment for creating DREZ lesions. The lesions are precisely placed with only a bipolar electrode. Postoperative complications are rare and transient. We believe that the junctional coagulation includes the entire dorsolateral sulcus and DREZ structures important for deafferentation pain.     

Chronic stimulation of the K?lliker-Fuse nucleus region for relief of intractable pain in humans.

Chronic electrical stimulation in the periventricular or periaqueductal gray matter regions and the thalamic somatosensory relay nuclei (ventralis posteromedialis and ventralis posterolateralis) provides long-term pain relief in about 50% of patients with intractable pain refractory to other conservative and/or surgical measures. To enhance the success of electrical stimulation in relief of pain, alternative brain and brain-stem targets have been sought. A series of laboratory studies indicated that the K?lliker-Fuse nucleus and the parabrachial region may provide appropriate alternatives to the "classic" targets. This report describes six patients with intractable chronic pain of nociceptive or central origin, in whom an electrode was stereotactically implanted in the region of the K?lliker-Fuse nucleus. K?lliker-Fuse nucleus stimulation alone or in combination with stimulation in the periaqueductal/periventricular gray matter region or the somatosensory thalamic nuclei provided excellent pain relief in three of the six patients.     

Motor cortex stimulation in patients with deafferentation pain: activation of the posterior insula and thalamus

OBJECT: The mechanisms underlying deafferentation pain are not well understood. Motor cortex stimulation (MCS) is useful in the treatment of this kind of chronic pain, but the detailed mechanisms underlying its effects are unknown. METHODS: Six patients with intractable deafferentation pain in the left hand were included in this study. All were righthanded and had a subdural electrode placed over the right precentral gyrus. The pain was associated with brainstem injury in one patient, cervical spine injury in one patient, thalamic hemorrhage in one patient, and brachial plexus avulsion in three patients. Treatment with MCS reduced pain; visual analog scale (VAS) values for pain were 82 +/- 20 before MCS and 39 +/- 20 after MCS (mean +/- standard error). Regional cerebral blood flow (rCBF) was measured by positron emission tomography with H2(15)O before and after MCS. The obtained images were analyzed with statistical parametric mapping software (SPM99). RESULTS: Significant rCBF increases were identified after MCS in the left posterior thalamus and left insula. In the early post-MCS phase, the left posterior insula and right orbitofrontal cortex showed significant rCBF increases, and the right precentral gyrus showed an rCBF decrease. In the late post-MCS phase, a significant rCBF increase was detected in the left caudal part of the anterior cingulate cortex (ACC). CONCLUSIONS: These results suggest that MCS modulates the pathways from the posterior insula and orbitofrontal cortex to the posterior thalamus to upregulate the pain threshold and pathways from the posterior insula to the caudal ACC to control emotional perception. This modulation results in decreased VAS scores for deafferentation pain.     

Subcortical electrical stimulation for control of intractable pain in humans. Report of 122 cases (1970-1984)

Chronic electrical stimulation of the subcortical area of the brain by implanted electrodes provides satisfactory control of a number of intractable pain syndromes that are refractory to medication. This series of 122 patients who underwent electrode implantation for the control of severe chronic pain was evaluated over a follow-up period of 2 to 14 years. Of the 65 patients with pain of peripheral origin, who were treated with stimulation of the periaqueductal gray region (PAG), 50 obtained successful pain control. Of 76 patients with a deafferentation pain syndrome, 44 obtained control of the dysesthesia with stimulation of the subcortical somatosensory region. Nineteen patients with both leg and back pain received electrodes in the PAG and the somatosensory regions; whereas back pain was relieved by PAG stimulation, dysesthetic leg pain was controlled more effectively by somatosensory region stimulation. The electrical stimulation technique appears to provide long-term pain control safely, with few side effects or complications.     

The Changes of c-Fos Expression by Motor Cortex Stimulation in the Deafferentation Pain Model

The effect of motor cortex stimulation (MCS) therapy for deafferentation pain was evaluated based on c-Fos, a known pain marker. Nineteen mature cats weighing 1.5–3.5 kg were used. Cats were divided into three groups: a deafferentation pain group in which the left trigeminal ganglion was destroyed, an MCS group in which MCS was used following destruction of the trigeminal ganglion, and a control group. Sites and levels of c-Fos expression were examined immunohistochemically. The percentage of c-Fos-positive cells in the left spinal nucleus of the trigeminus, the bilateral insula, and the bilateral operculum increased in both the deafferentation pain and the MCS groups. There were no statistically significant differences between these groups. In the cingulate gyrus, the percentage of c-Fos-positive cells increased bilaterally in the deafferentation pain group and the MCS group, but the increase was greater in the MCS group. The increase in c-Fos-positive cells in the left spinal nucleus of the trigeminus in the deafferentation group may reflect reported electrical hyperactivity. The cingulate gyrus, insula, and parietal operculum were activated after deafferentation. This change (increase in c-Fos positive cells) is related to the development of deafferentation pain. Pain relief due to MCS is not dependent on the suppression of the activated left spinal nucleus of the trigeminus or the descending analgesic mechanism of the brain stem. Activation of the cingulate gyrus appears to be a factor in the analgesic mechanism of MCS.     

Motor cortex stimulation in the treatment of deafferentation pain. I. Localization of the motor cortex

MRI and electrophysiological techniques to localize the primary motor cortex (MC) were performed on patients considered for MC stimulation for the treatment of deafferentation pain. The representation and trajectory of the rolandic fissure (RF) were accurately localized by external cranial landmarks and radiopaque fiducials superimposed on oblique MRI sections. In addition, the scalp distribution of the corticocortical responses elicited by acute epidural stimulation [motor cortex (MC) in frontal and sensory cortex (SC) in parietal scalp regions], and analgesic responses at the topographical representation of the painful periphery elicited by subacute epidural stimulation were found to be simple and reliable procedures to localize MC, SC and RF.     

Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies

Chronic motor cortex stimulation (CMCS) has provided satisfactory control of pain in patients with central or trigeminal neuropathic pain. We used this technique in 3 patients with intractable phantom limb pain after upper limb amputation. Functional magnetic resonance imaging (fMRI) correlated to anatomical MRI permitted frameless image guidance for electrode placement. Pain control was obtained for all the patients initially and the relief was stable in 2 of the 3 patients at 2 year follow-up. CMCS can be used to relieve phantom limb pain. fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication.