Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data.

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 (eight new patients and five reinterventions) were operated by a technique including localisation 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 ten of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the three 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 zooster. 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 localisation 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.     

Motor cortex stimulation for chronic neuropathic pain: a preliminary study of 10 cases

There is growing evidence to support the use of motor cortex stimulation (MCS) in the management of patients with chronic neuropathic pain. A prospective audit of ten patients using a modified staged technique for motor cortex implantation provides further evidence for the analgesic effectiveness of this technique. Ten patients suffering from phantom limb pain (n=3), post stroke pain (n=5), post traumatic neuralgia secondary to gunshot injury to the brain stem (n=1) and brachyalgia secondary to neuro-fibromatosis (n=150% pain relief) and long-term benefit in 4/5 of patients who initially responded to intermittent cortical stimulation (longest follow up 31 months after implantation). Of those patients who benefited two had post stroke pain, two phantom limb pain and one post-traumatic neuralgia. We conclude that motor cortex stimulation is an effective analgesic intervention in some patients with chronic neuropathic pain, but it is difficult if not impossible to predict those patients who may respond to treatment prior to implantation. Randomised controlled trials are now urgently needed to test the effectiveness of motor cortex stimulation under double-blind conditions.     

Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy

Thirty-one patients with medically refractory neuropathic pain were included in a prospective evaluation of motor cortex stimulation. The long-term outcome was evaluated using five variables: (a) rate (percentage) of pain relief, (b) pain scores as assessed on VAS, (c) postoperative decrease in VAS scores, (d) reduction in analgesic drug intake, (e) a dichotomic (yes/no) response to the question whether the patient would accept, under similar circumstances, to be operated on again. Pain relief was rated as excellent (>70 % pain relief) in 10 % of cases, good (40-69 %) in 42 %, poor (10-39 %) in 35 % and negligible (0-9 %) in 13 %. Intake of analgesic drugs was decreased in 52 % of patients and unchanged in 45 % (unavailable data in 3 %), with complete withdrawal of analgesic drugs in 36 % of patients. Twenty-one patients (70 %) declared themselves favourable to re-intervention if the same beneficial outcome could be guaranteed. Neither preoperative motor status, pain characteristics, type or localisation of lesions, quantitative sensory testing, Somatosensory Evoked Potentials, nor the interval between pain and surgery were found to predict the efficacy of MCS. The level of pain relief, as evaluated in the first month following implantation was a strong predictor of long-term relief (regression analysis, R=0.744; p<0.0001). These results confirm that MCS can be a satisfactory and durable alternative to medical treatments in patients with refractory pain, and suggest that the efficacy of MCS may be predicted in the first month of therapy.     

Motor cortex stimulation for central pain following a traumatic brain injury

Central pain can occur in any lesions along the central nervous system affecting the spinothalamocortical pathway. Although diverse etiologies have been reported to cause central pain, there are few reports on the occurrence and surgical treatment of central pain following a traumatic brain injury (TBI). This paper describes the occurrence of central pain following a severe TBI, in which the diagnosis of central pain was typically delayed due to the patient's decreased ability to express his pain for severe aphasia as a neurological sequela. The severe burning pain, deep pressure-like pain, and deep mechanical allodynia, which presented over the contralateral side to the TBI, were successfully relieved with motor cortex stimulation (MCS). The analgesic effect of stimulation was found to be long lasting and was still present at the 12-month follow up. As shown in this patient, the occurrence of central pain syndrome should be considered by physicians caring for TBI patients, and a comprehensive, systematic study will be needed to determine the prevalence of central pain after a TBI.     

Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience

Chronic subthreshold stimulation of the contralateral precentral gyrus is used in patients with intractable neuropathic pain for more than 15 years. The aim of this study was to analyse retrospectively our own patient group with long term follow-up of 10 years. Seventeen patients with chronic neuropathic pain were treated with contralateral epidural stimulation electrodes. In 10 cases, trigeminal neuropathic pain (TNP) and in seven cases post-stroke pain (PSP) were diagnosed. The placement of the electrodes was performed in local anaesthesia using neuronavigation and intraoperative neuromonitoring. A test trial of minimum one week including double-blind testing was conducted and pain intensity was measured using a visual analogue scale (VAS). Correct placement of the electrode was achieved in all patients using intraoperative neurophysiological monitoring. Double-blind testing was able to identify 6 (35%) non-responders. In 5 of 10 (50%) with TNP and 3 of 7 (43%) with PSP a positive effect with pain reduction > or = 50% was observed. The mean follow-up period was 3.6 years (range 1-10 years) and includes a patient with 10 years of positive stimulation effect. Stimulation of the motor cortex is a treatment option for patients with chronic neuropathic pain localized in the face or upper extremity. Double-blind testing can identify non-responders. Patients with TNP profit more than patients with PSP. The positive effect can last for ten years in long-term follow-up.     

运动区皮质刺激治疗顽固性丘脑痛的初步研究

目的探讨运动区皮质刺激治疗顽固性丘脑痛的手术方法及效果。方法以条形电极对3例顽固性丘脑痛患者行对侧运动区皮质刺激并植入电子刺激器进行慢性电刺激。结果3例患者术后症状明显缓解,疼痛视觉模拟评分(VAS评分)较术前显著下降,无偏瘫、癫痫等并发症发生。结论运动区皮质刺激是控制顽固性丘脑痛的有效方法,中央沟精确定位及调节合适的刺激参数尤为重要。     

Chronic neuropathic pain in spinal cord injury: Efficiency of deep brain and motor cortex stimulation therapies for neuropathic pain in spinal cord injury patients

ObjectivesIn spite of all the scientific advances in pharmacological research, a great number of patients cannot efficiently manage their chronic pain with conventional pharmacological treatments. Brain stimulation techniques have considerably improved these last 10 years. These techniques could be an interesting option after a rigorous selection of patients. We aim to evaluate the efficacy of brain stimulation (deep brain stimulation [DBS] and motor cortex stimulation [MCS]) within the framework of neuropathic pain management in spinal cord injury (SCI) patients and elaborate some recommendations.Material and methodThe methodology used, proposed by the French Society of Physical Medicine and Rehabilitation (SOFMER), includes a systematic review of the literature, the gathering of information regarding current clinical practices and a validation by a multidisciplinary panel of experts.ResultsDBS is more effective on nociceptive pain than deafferentation pain. For the central pain of SCI patients, the long-term efficacy of DBS is quite low (three patients out of 19, amounting to 16%). MCS seems to have an interesting potential with a long-term efficacy of 57% (four patients out of seven), with less complications than DBS.ConclusionFor central pain in SCI patients, there is no sufficient level of evidence to validate the use of DBS. There is however a low level of evidence for MCS. These results must be validated by larger comparative or controlled versus placebo clinical studies.     

Deep brain stimulation for the alleviation of post-stroke neuropathic pain

Our aim was to asses the efficacy of deep brain stimulation in post-stroke neuropathic pain. Since 2000, 15 patients with post-stroke intractable neuropathic pain were treated with deep brain stimulation of the periventricular gray area (PVG), sensory thalamus (Ventroposterolateral nucleus-VPL) or both. Pain was assessed using both a visual analogue scale and the McGill's pain questionnaire. VAS scores show a mean improvement of 48.8% (SD 8.6%). However, there is a wide variation between patients. This study demonstrates that it is an effective treatment in 70% of such patients.     

Deep brain stimulation for chronic neuropathic pain: long-term outcome and the incidence of insertional effect

We conducted a retrospective analysis of long-term results of deep brain stimulation (DBS) for the treatment of neuropathic pain. Twenty-one patients had electrodes implanted in the ventrocaudalis thalamic nucleus (Vc) (n=13) or in both Vc and periaqueductal/periventricular gray matter (PAG/PVG) (n=8). After insertion of the electrodes, 9 patients (43%) had a substantial reduction in pain scores in the absence of stimulation (insertional effect). The effects of stimulation were studied right after surgery or upon return of the patients' pain after electrode insertion (stimulation trials). Patients with a greater than 50% reduction in pain scores were implanted with a pulse generator (IPG). Of interest, patients who had an insertional effect had a trend towards a successful stimulation trial (p=0.08). Overall, 13 of the 21 patients operated (62%) had a successful stimulation trial and received an IPG (12 with electrodes in Vc and one in both Vc and PAG/PVG). Seven patients (33%) did not benefit from stimulation and had the electrodes removed. One patient experienced a prolonged insertional effect and has not required stimulation. Of the 13 patients that received an IPG, 8 discontinued stimulation during the first year of treatment. Only 5 patients maintained long-term benefit (4 with stimulation in Vc and one in both Vc and PAG/PVG). The relatively low efficacy of DBS for the treatment of neuropathic pain stresses the need for further investigation and the exploration of new surgical targets.     

Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos‐IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos‐IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain.     

Motor and parietal cortex stimulation for phantom limb pain and sensations

Limb amputation may lead to chronic painful sensations referred to the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2 mA, 15 min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. Anodal tDCS of M1 induced a selective short-lasting decrease of PLP, whereas cathodal tDCS of PPC induced a selective short-lasting decrease of nonpainful phantom sensations; stump pain and telescoping were not affected by parietal or by motor tDCS. These findings demonstrate that painful and nonpainful phantom limb sensations are dissociable phenomena. PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.     

Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain

The aim of the present study has been to assess the responsiveness of various types of chronic pain to opioids given i.v. and tested against placebo in a double-blind, randomized fashion. Pain classified as primary nociceptive was effectively alleviated (P greater than 0.001) while neuropathic deafferentation pain was not significantly influenced by morphine or equivalent doses of other opioids. Also 'idiopathic' pain, defined as chronic pain with no or little demonstrable pathology, failed to respond. The results were not related to whether the patients were regular users of narcotic analgesics or not. The outcome of our double-blind opioid test has proved useful to justify a continued, or discontinued, use of narcotic medication in individual patients. It may also support the indication and choice of invasive stimulation procedures (spinal cord or brain). The results of the study illustrate the misconception of chronic pain as an entity and highlight the importance of recognizing different neurobiological mechanisms and differences in responsiveness to analgesic drugs as well as to non-pharmacological modes of treatment. The opioid test has thus become a valuable tool in pain analysis and helpful as a guide for further treatment.     

Modulation of neuronal activity after spinal cord stimulation for neuropathic pain; H215O PET study

Spinal cord stimulation (SCS) is an effective therapy for chronic neuropathic pain. However, the detailed mechanisms underlying its effects are not well understood. Positron emission tomography (PET) with H₂¹⁵O was applied to clarify these mechanisms. Nine patients with intractable neuropathic pain in the lower limbs were included in the study. All patients underwent SCS therapy for intractable pain, which was due to failed back surgery syndrome in three patients, complex regional pain syndrome in two, cerebral hemorrhage in two, spinal infarction in one, and spinal cord injury in one. Regional cerebral blood flow (rCBF) was measured by H₂¹⁵O PET before and after SCS. The images were analyzed with statistical parametric mapping software (SPM2). SCS reduced pain; visual analog scale values for pain decreased from 76.1 ± 25.2 before SCS to 40.6 ± 4.5 after SCS (mean ± SE). Significant rCBF increases were identified after SCS in the thalamus contralateral to the painful limb and in the bilateral parietal association area. The anterior cingulate cortex (ACC) and prefrontal areas were also activated after SCS. These results suggest that SCS modulates supraspinal neuronal activities. The contralateral thalamus and parietal association area would regulate the pain threshold. The ACC and prefrontal areas would control the emotional aspects of intractable pain, resulting in the reduction of neuropathic pain after SCS.     

Motor cortex stimulation reduces hyperalgesia in an animal model of central pain

Electrical stimulation of the primary motor cortex has been used since 1991 to treat chronic neuropathic pain. Since its inception, motor cortex stimulation (MCS) treatment has had varied clinical outcomes. Until this point, there has not been a systematic study of the stimulation parameters that most effectively treat chronic pain, or of the mechanisms by which MCS relieves pain. Here, using a rodent model of central pain, we perform a systematic study of stimulation parameters used for MCS and investigate the mechanisms by which MCS reduces hyperalgesia. Specifically, we study the role of the inhibitory nucleus zona incerta (ZI) in mediating the analgesic effects of MCS. In animals with mechanical and thermal hyperalgesia, we find that stimulation at 50 μA, 50 Hz, and 300 μs square pulses for 30 minutes is sufficient to reverse mechanical and thermal hyperalgesia. We also find that stimulation of the ZI mimics the effects of MCS and that reversible inactivation of ZI blocks the effects of MCS. These findings suggest that the reduction of hyperalgesia may be due to MCS effects on ZI.     

Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain: a pilot study.

Only about 60-70% of well selected patients with neuropathic pain syndromes of peripheral origin enjoy sufficient pain relief with spinal cord stimulation (SCS). Since recent animal experiments have demonstrated that the GABA-B receptor is pivotal in the effect of SCS on certain neuropathic symptoms, the use of baclofen as an adjunct to stimulation emerged as an option in patients not responding satisfactorily to SCS. Forty-eight patients with neuropathic pain of peripheral origin responding poorly to SCS were enrolled in a study with intrathecal baclofen; in a few cases adenosine was also tried. Twenty patients reported significant pain reduction at bolus trials and were offered implantation of a drug pump. Seven patients subsequently had pumps implanted together with SCS and four had pumps alone. Three patients had only peroral baclofen therapy as an adjunct to SCS. The 14 patients continuing with baclofen therapy as an adjunct to SCS, or alone, were followed for an average of 35 months after pump implant. The group with SCS+pump n=5; 2 explanted) reported an average decrease of pain ratings from VAS 82 to 33. The group with i.t. baclofen only had a pain decrease from VAS 63 to 33, while the three patients with peroral baclofen+SCS had less benefit from drug therapy. Adjunctive drug therapy for patients with unsatisfactory pain relief by SCS may offer a possibility to enhance pain alleviation.