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.     

Efficacy of motor cortex stimulation for intractable central neuropathic pain: comparison of stimulation parameters between post-stroke pain and other central pain

Motor cortex stimulation (MCS) has now become the preferred option for neurosurgical management of intractable central neuropathic pain such as post-stroke pain and trigeminal neuropathic pain. However, the efficacy of MCS for other central neuropathic pain such as pain resulting from spinal cord or brainstem lesions is unclear. We retrospectively reviewed 11 consecutive patients with intractable central neuropathic pain who underwent MCS in our institution. Eight patients had poststroke pain caused by thalamic hemorrhage (n = 5) or infarction (n = 3) (thalamic group). Two patients had postoperative neuropathic pain caused by spinal cord lesions, and one patient had facial pain caused by a brainstem lesion associated with multiple sclerosis (brainstem-spinal group). Visual analog scale and stimulation parameters were evaluated at 1 and 6 months postoperatively. MCS was effective for six of eight patients in the thalamic group, and all three patients in the brainstem-spinal group. These efficacies continued for 6 months after surgery without significant change in the stimulation parameters compared with the parameters at 1 month in both groups. The mean amplitude at 1 month and frequency at 6 months after surgery were significantly higher in the brainstem-spinal group than the thalamic group, although the patient number was small. MCS is effective for other central neuropathic pain, but higher intensity stimulation parameters may be necessary to gain adequate pain reduction.     

Percutaneous epidural electrical stimulation of the spinal cord for intractable pain--with special reference to deafferentation pain

In a study of 44 patients with different types of chronic pain, mostly associated with deafferentation, chronic percutaneous epidural spinal stimulation has proved useful treatment achieving an initial 52% incidence of pain amelioration overall. Long-term result showed at six months in 86%, at 1 year in 90%, although technical problems, which included electrode displacement and required minor operative readjustment, affected 48% of those permanently implanted. No other complications were seen. Success bore no relationship to quality of pain reported by the patients or to duration of pain. The patients with denervation caused by nerve or root lesions responded better than those with cord lesions even though electrical paresthesia were delivered to the area of pain in each case. A decline in effectiveness with time was noted in small numbers of our cases despite persistence of paresthesia in the area of pain. It is suggested that late failure reflects plasticity of the nervous system in adapting to new inputs. Morphine study was carried out in some of these patients. Morphine did not help to ameliorate the pain in many cases with deafferentation pain. And also Naloxone was administered during successful pain-relieving stimulation. This did not result in recurrence of pain. The Somato Sensory Responses were recorded in 25 patients before and during neurostimulation. When stimulation was applied the late component was suppressed in most of those who enjoyed a good result. The early component was not changed in those patients even during stimulation. These results suggest that spinal cord stimulation would suppress the denervative hypersensitivity of dorsal horn in the patients with deafferentation pain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei of patients with deafferentation pain

Electrical activity was recorded from single cells in the thalamus of 10 patients with chronic pain associated with deafferentation. Under local anesthesia, these patients underwent either electrode implantation or thalamotomy for treatment of their pain. In eight of the 10 patients, single units were identified as discharging spontaneously in high-frequency, often rhythmic, bursts. The discharges were of two types: short bursts comprised of two to six spikes with a burst frequency of one to four per second; and long trains of 30 to 80 spikes of similar frequency. Reconstruction of electrode trajectories indicated that recordings were made from the region corresponding to the lateral aspect of the mediodorsal thalamic nucleus, the central lateral nucleus, a small part of the central median nucleus, and the parafascicular nucleus. In the eight patients in whom spontaneous neuronal burst activity was exhibited, it was impossible to study activity evoked by natural cutaneous stimulation due to the continuous spontaneous neuronal discharges. Both animal and human studies have suggested that pain related to deafferentation is accompanied by spontaneous hyperactivity in the dorsal horn of the spinal cord and in the ventral posterior thalamic nuclei. The authors present evidence of spontaneous neuronal hyperactivity in the intralaminar thalamic nuclei of patients with pain related to deafferentation. The findings suggest that spontaneous neuronal discharge in patients with pain related to deafferentation is more widespread in the central nervous system than has been previously appreciated. The results have important implications for the surgical treatment of chronic pain.     

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.     

Clinical and electrophysiological expression of deafferentation pain alleviated by dorsal root entry zone lesions in rats

OBJECT: The aims of this study were to construct an animal model of deafferentation of the spinal cord by brachial plexus avulsion and to analyze the effects of subsequent dorsal root entry zone (DREZ) lesions in this model. To this end, the authors measured the clinical and electrophysiological effects of total deafferentation of the cervical dorsal horn in rats and evaluated the clinical efficacy of cervical DREZ lesioning. METHODS: Forty-three Sprague-Dawley rats were subjected to total deafferentation of the right cervical dorsal horn by performing a posterior rhizotomy from C-5 to T-1. The clinical effects of this deafferentation, namely self-directed mutilations consisting of scraping and/or ulceration of the forelimb skin or even autotomy of some forelimb digits, were then evaluated. As soon as some of these clinical signs of pain appeared, the authors performed a microsurgical DREZ rhizotomy ([MDR], microincision along the deafferented DREZ and dorsal horn). Before and after MDR, single-unit recordings were obtained in the deafferented dorsal horn and in the contralateral (healthy) side. The mean frequency of spontaneous discharge from the deafferented dorsal horn neurons was significantly higher than that from the healthy side (36.4 Hz compared with 17.9 Hz, p = 0.03). After deafferentation, 81.4% of the rats developed clinical signs corresponding to pain following posterior rhizotomy. Among these animals, scraping was observed in 85.7% of cases, ulceration (associated with edema) in 37.1%, and autotomy in 8.5%. These signs appeared a mean 5.7 weeks (range 1-12 weeks) after deafferentation. Thirteen rats benefited from an MDR; nine (69%) experienced a complete cure, that is, a total resolution of scraping or ulceration (a mean 4.6 weeks after MDR). In contrast, only one of 11 sham-operated animals showed signs of spontaneous recovery (p = 0.01). CONCLUSIONS: These results emphasize the role of the spinal dorsal horn in the genesis of deafferentation pain and suggest that dorsal horn deafferentation by cervical posterior rhizotomy in the rat provides a reliable model of chronic pain due to brachial plexus avulsion and its suppression by MDR.     

Spinal epidural stimulation for central pain caused by spinal cord lesion]

Epidural spinal cord stimulation was carried out in 4 patients with denervation caused by spinal cord lesion, and we reviewed previously reported cases. Initial result showed at 1 week in 100% of our cases, but about 1/3 of the cases, even those with the same denervation caused by spinal cord lesion, had no pain relief at this stage in previously reported cases. In our cases, excellent pain relief was gained temporarily, even though the painful area and the spinal cord lesion were separated somatotopically in 2 cases (case 3, 4). Temporary success bore no relationship to quality and duration of pain. In all cases except case 1, a rapidly decreasing effectiveness was noted, and finally no pain relief was gained at all after 4, 3 and 5 months, respectively. In case 1 there was persistent pain relief estimated at 70-80% after 19 months, only when the spinal cord was stimulated. Epidural stimulation also produced sensations in the painful area. Spinal cord stimulation would suppress at least the dorsal horn neurons which were destroyed by various kinds of diseases. A decline in effectiveness with time would occur due to essential causes of the deafferentation pain, such as anatomical and regeneration factors.     

Spinal cord stimulation in management of chronic pain. A 9-year experience

Between 1978 and 1986, 109 patients with chronic pain underwent spinal cord stimulation (SCS) at the authors' institute as part of their pain treatment program. The results of SCS in these patients at the end of the test period and at the latest follow-up examination are analyzed in relation to the etiology of their pain. In 40 patients pain was associated with an obstructive peripheral vasculopathy, in 10 with a previous herpes zoster infection, in 15 with an incomplete traumatic spinal cord lesion, in nine with root and/or nerve damage, in 11 with cancer, and in 19 with previous back surgery. The etiology of the pain in five patients was uncertain. This experience supports the conclusion that the best indications for SCS are vasculopathic pain and post-herpetic neuralgia. No clinical usefulness was found for SCS in cancer pain or in central deafferentation types of pain.     

Conversion disorder mimicking Dejerine-Roussy syndrome (thalamic stroke) after spinal cord stimulation

OBJECTIVE: Dejerine-Roussy syndrome is a complex of various signs and symptoms in patients suffering from central thalamic pain, usually secondary to a vascular etiology. We describe a patient presenting with the potentially devastating signs and symptoms of thalamic stroke, at least temporally related to spinal cord stimulator implantation. The etiology of the patient's affliction was subsequently revealed to be a conversion disorder.Case report A 37-year-old woman presented for spinal cord stimulation as treatment of her brachial plexopathy after failure of conservative therapy. Before implantation, she underwent a clinical interview with a psychologist and psychometric testing. No psychological pathology was detected. Trial and permanent implantation of the cervical stimulator lead and pulse generator were uneventful. Eleven days after receiving the permanent implant, the patient experienced right-sided hemicorporal numbness and burning dysesthesia. The patient was admitted, and a diagnosis of Dejerine-Roussy syndrome (thalamic stroke) was made. She was discharged, and her symptomatology waxed and waned over a period of weeks. The patient was subsequently admitted for psychiatric evaluation because of anxiety attacks. During her protracted admission, her psychiatrists strongly suspected a conversion disorder. The stimulator was removed, and the patient received supportive care only. Within 6 months, sensory symptoms and all motor deficits had completely resolved. CONCLUSIONS: Despite careful preoperative evaluation, latent psychosocial issues may limit the effectiveness of spinal cord stimulation. We present a case of conversion disorder masquerading as Dejerine-Roussy syndrome after spinal cord stimulation. The implications of the failure of preoperative psychological evaluation and screening to avert implantation are discussed.     

Motor cortex stimulation for post-stroke pain: comparison of spinal cord and thalamic stimulation

We analyzed the effects of spinal cord stimulation (SCS), deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (VC) and motor cortex stimulation (MCS) in 45 patients with post-stroke pain. Satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels (7% by SCS, 25% by DBS and 48% by MCS). A painful sensation was sometimes produced by stimulation of the VC as well as the post-central, pre-central and pre-frontal cortices. Such a sensation occurred less frequently as the stimulation site was moved to higher levels (50% at the VC, 39% at the post-central cortex, 6% at the pre-central cortex and 3% at the pre-frontal cortex). These findings imply that abnormal processing of nociceptive information develops at the level of deafferentation and spreads to higher levels to a varying extent. This may be one of the reasons why satisfactory pain control was obtained more frequently as the stimulation site was moved to higher levels.     

Therapeutic stereotactic procedures on the thalamus for pain

Summary Thalamotomy and electrical stimulation of a thalamic target as treatment for persistent pain are discussed. Thalamotomy is only rarely performed these days according to a questionnaire, given to some colleagues, about the type and the number of operations they performed in the years 1984, 1985 and 1986. The need for stimulation in the periventricular or periaqueductal grey for nociceptive pain is decreasing due to the advent of intraspinal and intraventricular administration of opioids. Nowadays medial and lateral ventro-posterior thalamic nuclei are frequently stimulated for treatment of deafferentation pain. Of 36 patients with deafferentation pain, 22 initially had benefit from this stimulation, but long-term success was only achieved in 11 (30%) of them. It was a general trend that the patients with an initial high pain relief score obtained the best long-term results.     

Epidural spinal cord stimulation for the treatment of neurogenic bladder

Summary The effect of percutaneous epidural spinal cord stimulation on neurogenic bladder has been evaluated on the basis of objective clinical and urodynamic criteria. Seven patients suffering from stable bladder and sphincter dysfunction due to spinal cord diseases of different causes of non-evolutive nature were examined. In some of them chronic pain or spasticity, or both, were also present.Spinal cord stimulation substantially improved micturition in six out of seven patients. Complete or almost complete relief of bladder spasticity, marked increase of bladder capacity, and reduction or abolition of residual urine were recorded. The beneficial effect on bladder and sphincter function is strictly dependent on the stimulation, though it can outlast it. It requires some weeks to reach its maximum. It is still obtained after 22 months of treatment (longest present follow-up).No changes of striatal activity and detrusor reflex were produced by spinal cord stimulation in two additional patients, treated for chronic pain but having intact bladder function.Partially supported by Ministry of Public Instruction.     

Pain relief from dorsal root entry zone lesions made with argon and carbon dioxide microsurgical lasers

Argon and carbon dioxide microsurgical lasers were used to produce lesions in the dorsal root entry zone (DREZ) experimentally in six cats and surgically in 21 patients who had denervation pain syndromes. The technique of producing lesions, the histological and physiological changes seen in the cat spinal cord, and the results of treatment in the clinical series are discussed. Lesions were produced within the DREZ without new involvement of the dorsal column system or corticospinal tract in all but one patient. Based on their subjective evaluation, two-thirds of the patients were relieved of more than 50% of their preoperative pain. These experimental results and clinical experience suggest that the argon and carbon dioxide lasers effectively produce localized microsurgical lesions in the DREZ. The concept that an abnormality involving either neurons in the substantia gelatinosa or internuncial fibers in Lissauer's tract is responsible for pain in patients with primary sensory nerve deafferentation is discussed.     

Thermocoagulation of the dorsal root entry zone for the treatment of intractable pain

The authors report the results of DREZ thermocoagulation in 35 patients since March 1980. This technique was applied not only in patients with deafferentation pain after brachial plexus avulsion, but also for postamputation phantom limb pain and pain caused by injury to the spine and spinal cord, by peripheral nerve lesions, and by multiple sclerosis. Independent of etiology, the duration of the pain syndrome, and the quality and projection of the pain, the overall results have been satisfactory and long-lasting.     

Thalamic sensory relay nucleus stimulation for the treatment of peripheral deafferentation pain

We applied chronic deep brain stimulation (DBS) of the thalamic nucleus ventralis caudalis (Vc) for the treatment of peripheral deafferentation pain. The subjects included 11 cases of phantom limb pain and 7 of root or nerve injury pain without phantom sensation. In the phantom limb pain patients, the spike density markedly increased in the same area of the Vc where microstimulation induced paresthesia in the part with phantom sensation. Reorganization of the receptive field representation within the Vc was also demonstrated by microrecording and microstimulation. In the root or nerve injury pain patients with severe allodynia and without phantom sensation, oscillating neural hyperactivity appeared when the allodynia was induced during single-cell recording in the Vc. In both groups stimulation of these areas with the DBS electrode was useful for achieving pain reduction. Inhibition of spinothalamic tract neurons, restoration of the original receptive field representation and modulation of thalamocortical rhythmic oscillations are proposed to play important roles in a possible mechanism of Vc-DBS for the treatment of deafferentation pain.     

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.     

Implantation of anterior sacral root stimulators combined with posterior sacral rhizotomy in spinal injury patients

Brindley-Finetech sacral anterior root stimulators combined with posterior sacral rhizotomy were implanted in 68 males and 28 females with spinal cord lesions. In 9 patients the electrodes were implanted extradurally in the sacrum, and in 90 patients they were implanted intradurally (3 patients had a second extradural implant after a first intradural implant). Three patients died from causes unrelated to the implant. Of the 93 surviving patients, 83 used their implants for micturition and 82 were fully continent. The mean bladder capacity increased from 206 ml preoperatively to 564 ml after the operation. Three patients had a preoperative vesicorenal reflux that disappeared after surgery. In all, 51 patients used the stimulator for defecation. Erection was possible with electrical stimulation in 46 males and was used for coitus by 17 couples. Secondary deafferentation at the level of the conus was performed four times. Three patients who had a cerebrospinal fluid leak were operated on again. Two implants had to be removed because of infection. Sacral anterior root stimulation combined with sacral deafferentation is a welcome addition to the treatment of neurogenic bladder in spinal cord injury patients.     

Spinal cord injuries induce changes in CB1 cannabinoid receptor and C-C chemokine expression in brain areas underlying circuitry of chronic pain conditions

Due to their involvement in neuro-modulatory processes, the endogenous cannabinoid system and chemokine network, which were shown to interact which each other, are potential key elements in the cascades underlying central neuropathic pain development after spinal cord injury (SCI). Expression profiles of cannabinoid receptor type-1 (CB(1)), and of the chemokines chemokine ligand 2 (C-C motif?) (CCL2), chemokine ligand 3 (C-C motif?) (CCL3), plus their main receptors CCR2 and CCR1, were investigated in brain regions related to pain, emotion, learning, and memory in a rat SCI paradigm of post-traumatic neuropathic pain. Immunoreactivity (IR) was investigated 7 days and 42 days after sham operation, and moderate (100-kdyn), and severe (200-kdyn) thoracic spinal cord contusion lesions. Hippocampal (HC) subregions, amygdaloid complex, anterior cingulate cortex (ACC), periaqueductal gray (PAG), and thalamic nuclei were analyzed. Seven days after lesioning, CB(1) IR was induced in thalamic nuclei and HC subregions (CA3 and dentate gyrus), and downregulated in amygdaloid nuclei, ACC, and PAG. On day 42, CB(1) IR remained elevated in the HC and thalamic areas, and was induced in ACC after 100-kdyn, but downregulated after 200-kdyn lesions. It remained reduced in the PAG of severely lesioned animals, paralleling their prolonged neuropathic pain-related behavior. Double-labeling revealed partial co-expression of CB(1) with the pain-related vanilloid receptor transient receptor potential vanilloid receptor 1 (TRPV1), and chemokines (CCL2 and CCL3). These chemokines were induced in the PAG, thalamus, and HC, especially in the chronic time course after severe SCI. Thus interactions of CB(1), C-C chemokines, and TRPV1 likely play a role in SCI-induced plastic changes in the brain, underlying emotional-affective pain responses and central pain development after spinal cord lesions.