Epidural Posterior Insular Stimulation Alleviates Neuropathic Pain Manifestations in Rats With Spared Nerve Injury Through Endogenous Opioid System.

OBJECTIVES: Neuropathic pain (NP) is defined as constant disabling pain secondary to a lesion or disease of the somatosensory nervous system. This condition is particularly difficult to treat because it often remains resistant to most treatment strategies. Despite the recent diversification of neurostimulation methods, some patients still suffer from refractory pain syndromes. The central role of the posterior insular cortex (PI) in the modulation of pain signaling and perception has been repeatedly suggested. The objective of this study is to assess whether epidural insular stimulation (IS) could reverse NP behavior. MATERIALS AND METHODS: A total of 53 adult Sprague-Dawley rats received left-sided spared nerve injury (SNI) or Sham-SNI to induce NP symptoms. Afterward, epidural electrodes were implanted over the right PI. After two weeks of postoperative recovery, three groups of SNI-operated rats each received a different stimulation modality: Sham-IS, low-frequency-IS (LF-IS), or high-frequency-IS (HF-IS). Behavioral and functional tests were conducted before and after IS. They comprised the acetone test, pinprick test, von Frey test, and sciatic functional index. An additional LF-IS group received a dose of opioid antagonist naloxone before IS. Intergroup means were compared through independent-samples t-tests, and pre- and post-IS means in the same group were compared through paired t-tests. RESULTS: We found a significant reduction of cold allodynia (p = 0.019), mechanical hyperalgesia (p = 0.040), and functional disability (p = 0.005) after LF-IS but not HF-IS. Mechanical allodynia only showed a tendency to decrease after LF-IS. The observed analgesic effects were reversed by opioid antagonist administration. CONCLUSION: These results suggest a significant reversal of NP symptoms after LF-IS and offer additional evidence that IS might be beneficial in the treatment of resistant NP syndromes through endogenous opioid secretion. Relying on our novel epidural IS model, further fine tuning of stimulation parameters might be necessary to achieve optimal therapeutic effects.

Somatosensory Thalamic Activity Modulation by Posterior Insular Stimulation: Cues to Clinical Application Based on Comparison of Frequencies in a Cat Model.

BACKGROUND: The posterior insula (PI) has been proposed as a potential neurostimulation target for neuropathic pain relief as it represents a key-structure in pain processing. However, currently available data remain inconclusive as to efficient stimulation parameters. OBJECTIVE: As frequency was shown to be the most correlated parameter to pain relief, this study aims to evaluate the potential modulatory effects of low frequency (LF-IS, 50 Hz) and high-frequency (HF-IS, 150 Hz) posterior insular stimulation on the activity of somatosensory thalamic nuclei. MATERIALS AND METHODS: Epidural bipolar electrodes were placed over the PI of healthy adult cats, and extracellular single-unit activities of nociceptive (NS), nonnociceptive (NN), and wide dynamic range (WDR) thalamic cells were recorded within the ventral posterolateral nucleus and the medial division of the thalamic posterior complex. Mean discharge frequency and burst firing mode were analyzed before and after either LF-IS or HF-IS. RESULTS: LF-IS showed a significant thalamic modulatory effects increasing the firing rate of NN cells (p ≤ 0.03) and decreasing the burst firing of NS cells (p ≤ 0.03), independently of the thalamic nucleus. Conversely, HF-IS did not induce any change in firing properties of the three recorded cell types. CONCLUSION: These data indicate that 50 Hz IS could be a better candidate to control neuropathic pain.

Validation of a New Arabic Version of the Neuropathic Pain Diagnostic Questionnaire (DN4).

The "Douleur Neuropathique 4 (DN4) questionnaire" was developed for screening neuropathic pain. The purpose of this work was to validate the DN4 questionnaire in the standard Arabic language. First, the questionnaire was translated and semantically adapted to Arabic according to the international guidelines for cross-cultural adaptation. Second, a prospective observational study was performed to validate this questionnaire. A total of 195 patients with chronic pain (n = 99 with neuropathic pain and n = 96 without neuropathic pain) were enrolled in the study. The internal consistency Kuder-Richardson's Formula 20 for the whole DN4 questionnaire was 0.86 (P < 0.001) and the intraclass correlation coefficient 0.99 (95% CI: 0.99 to 1.00). The test-retest reliability kappa coefficient for each item ranged from 0.92 to 1.00. Using a receiver-operating characteristic (ROC) curve analysis, the areas under the curve were 0.94 and 0.97 for the 7-item DN4 and 10-item DN4, respectively. A cut-off score of 3 resulted in a sensitivity of 97.0% and a specificity of 82.3% for the 7-item DN4, while a cut-off score of 5 for the 10-item DN4 resulted in a sensitivity of 93.0% and a specificity of 95.8%. Tingling, numbness, and hypoesthesia to touch and to pricking were the most discriminating pain items. The sensitivity and specificity of the 7-item DN4 and 10-item DN4 were not influenced by either pain severity or educational level. In conclusion, this new Arabic version DN4 questionnaire is a simple, reliable, and valid tool for discriminating between neuropathic and non-neuropathic pain. It represents a useful tool in clinical setting and population-based studies.

Intrathecal Baclofen Therapy for Refractory Spasticity: A Case Series.

BACKGROUND: Management of refractory spasticity symptoms remains a challenging task for clinicians. Intrathecal baclofen (ITB) therapy has emerged as a promising option for treating this condition. This study evaluates the effectiveness of ITB therapy in managing refractory spasticity symptoms. METHODS: A retrospective chart review was conducted on 34 patients with refractory spasticity symptoms who underwent ITB therapy at a single institution. The patients' demographics, clinical characteristics, and dosages were recorded. The primary outcome measures were the reduction in pain, improvement in mobility, decrease in spasm frequency, and alleviation of spasticity. RESULTS: ITB therapy successfully reduced pain, improved mobility, decreased spasm frequency, and alleviated spasticity. The mean daily administered dose was 245 µg (range: 88-510 µg, standard deviation:104). However, it was observed that the appropriate dosage of ITB therapy was patient-specific and time-sensitive. Moreover, side effects were observed when an incorrect dose was administered. CONCLUSIONS: ITB therapy is an effective and safe option for managing refractory spasticity symptoms. However, the appropriate dosage should be individualized and monitored closely to avoid side effects. This study highlights the importance of carefully considering the potential risks and benefits of ITB therapy for each patient.

Pentoxifylline significantly reduces radicular pain secondary to lumbar disc hernia: A prospective, randomized crossover, single-blind controlled pilot study.

BACKGROUND AND OBJECTIVES: Optimal medical treatment for low back pain, sometimes associated to radicular pain, has yet to be established. Herniated nucleus pulposus has been found to release TNFα, a pro-inflammatory cytokine involved in radiculopathy. Interestingly, Pentoxifylline (PTX), a phosphodiesterase inhibitor, blocks the activity of TNFα. The aim of this study is to assess the effectiveness of PTX when added to the treatment protocol of radiculopathy in lumbar disc herniation. METHODS: Fifty-eight patients with radicular pain secondary to a lumbar disc hernia were included in this prospective, randomized crossover, single-blind controlled study. PTX was added randomly to the same treatment protocol (ibuprofen + paracetamol + pregabalin) either during the first or the second 15 days of treatment. Patients' pain was assessed at day 15 via the Numeric Rating Scale (NRS) and the Patient's Global Impression of Change score (PGIC). D15 NRS value was considered as the primary outcome measure. RESULTS: Mean D15 NRS score was 3.2 ± 0.84 during the 15-days treatment with PTX, and 5,1 ± 0.97 during the 15-days treatment without PTX (p < 0.0001). During the 15 days treatment period with/without PTX, PGIC score was (7) in 19/3 patients, (6) in 30/10 patients, (5) in 7/27 patients and (4) in 2/18 patients respectively, difference being highly significant (p < 0.0000). CONCLUSION: Adjunction of PTX to the standard medical treatment of radicular pain associated with lumbar disc hernia seems to significantly decrease patients' pain intensity in addition to improving their global satisfaction with treatment.

Lumbar microdiscectomy: a clinicoradiological analysis of outcome.

BACKGROUND: The long-term outcome after lumbar microdiscectomy (LMD) may be affected by low back pain (LBP) and segmental instability, the determinants of which remain unclear. We sought to analyze the interaction between clinical, functional, and radiological variables and their impact on patient outcome. METHODS: All patients who underwent LMD in 2004-2005 were invited to participate in this retrospective cohort study. Patients were re-evaluated clinically and radiologically after a three to five year follow-up. RESULTS: Forty-one of 97 eligible patients were enrolled. Twelve patients (29.3%) reported moderate-to-severe sciatica, 12 (29.3%) had moderate LBP, and 13 (31.7%) exhibited clinical evidence of segmental instability. Thirty-eight patients (92.7%) had minimal disability and 3 (7.3%) had moderate disability. Twenty-three patients (56.1%) were fully satisfied, while 18 (43.9%) had only partial satisfaction, having expected a better outcome. Thirty-three patients (80.5%) returned to full-time work. Median disc space collapse (DSC) was 20% (range 5-66%) and L4-L5 was particularly affected. Prevalence of Modic changes increased from 46.3% to 78% with type 2 predominance. Multivariate logistic regression analysis identified the following negative prognostic factors: female sex, young age, lack of regular exercise, and chronic preoperative LBP. There was no correlation between the course of Modic changes, DSC, and patient outcome. CONCLUSION: Although many patients may be symptomatic following LMD, significant disability and dissatisfaction are uncommon. Female sex, young age, lack of exercise, and chronic preoperative LBP may predict a worse outcome. Disc collapse is a universal finding, particularly at L4-L5. Neither DSC nor Modic changes seem to affect patient outcome.

Chronic sub-dural hematomas: twist drill craniostomy with a closed system of drainage, for 48 hours only, is a valuable surgical treatment.

Twist drill craniostomy with closed drainage system for 48-hour duration is an effective treatment of chronic subdural hematomas.

Outcome and Prognosis of Microsurgical Decompression in Idiopathic Severe Common Fibular Nerve Entrapment: Prospective Clinical Study.

OBJECTIVE: Compression of the common fibular nerve at the level of the fibular neck is considered to be the most frequent lower limb entrapment syndrome, which can be either idiopathic or secondary. Decompressive surgery is indicated only after failure of conservative treatment and/or severe neurologic deficit. The effectiveness of microsurgical decompression has been established only for secondary entrapment syndrome. The aim of this study is to assess the results of microsurgical decompression and establish the prognosis of idiopathic severe common fibular nerve entrapment. METHODS: Fifteen patients were included in this prospective clinical study and were followed at day 1 after surgery and later at 1, 6, and 12 months. More than half (64.3%) of patients had a total motor deficit (0/5). The median motor function preoperatively was 0/5. The average time of conservative treatment before surgery was 25.7 days (range 5-110 days). One patient refused surgical management. RESULTS: Thirteen out of 14 patients who underwent surgery showed significant motor function improvement. The median motor strength at 12 months was 4.5/5. Half of the patients regained normal motor function. The only patient who did not improve had the longest time to surgery interval (110 days). The patient who refused surgery showed no improvement (0/5 at 12 months). CONCLUSIONS: Microsurgical decompression should be considered early in the context of severe idiopathic common fibular nerve entrapment in order to get a favorable outcome.

Impact of the lunar cycle on the incidence of intracranial aneurysm rupture: myth or reality?

OBJECTIVE: To analyze the impact of the lunar cycle and season on the incidence of aneurysmal subarachnoid hemorrhage (SAH). PATIENTS AND METHODS: The medical records of 111 patients who were admitted over a 5-year period to our department because of aneurysmal SAH were retrospectively reviewed. The date of aneurysm rupture was matched with the corresponding season and moon phase. RESULTS: An incidence peak for aneurysm rupture (28 patients) was seen during the phase of new moon, which was statistically significant (p < 0.001). In contrast, no seasonal variation in the incidence of SAH was observed. CONCLUSION: The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH.

Differential effect of motor cortex stimulation on unit activities in the ventral posterior lateral thalamus in cats.

Although motor cortex stimulation (MCS) is being increasingly used to treat chronic refractory neuropathic pain in humans, its mechanisms of action remain elusive. Studies in animals have suggested the involvement of subcortical structures, in particular, the thalamus. Most of these studies have been performed in rats, a species presenting significant differences in thalamic anatomy and function relative to primates, in particular, a very limited number of thalamic GABA interneurons. The aim of this study was to investigate the effects of MCS on single-unit activities of the thalamic ventral posterior lateral (VPL) nucleus in cats, which contains substantial numbers of GABA interneurons. Spontaneous and evoked activities of VPL units were studied before and after MCS. Motor cortex stimulation induced significant depression of the wide-dynamic-range (WDR) cells' firing rate, concomitant with activity enhancement of nonnociceptive (NN) units. More than half of WDR cells showed a significant decrease in the firing rate, while a similar proportion of NN units exhibited the opposite after-effect. Maximal firing attenuation of WDR cells occurred when the MCS location matched somatotopically their receptive field. Repetition of MCS runs led to an accentuation of WDR depression. After peripheral stimulation, evoked activity in each cell showed MCS effects similar to those observed in spontaneous activity. These data demonstrate a selective top-down inhibition by MCS of nonspecific nociceptive (WDR) cells, enhanced by somatotopic concordance and stimulation repetition, in parallel to facilitation of NN cells. These 2 outcomes may play a role in the complex analgesic effect of MCS observed in neuropathic pain conditions.

Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model.

BACKGROUND: Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. METHODS: Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value before nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological study at week 12. RESULTS: Our results showed that MCS enhances functional recovery, nerve regeneration, and muscle reinnervation starting week 4 compared with the control group (P < 0.05). The MCS induces higher reinnervation rates even compared with peripheral stimulation, with better results in the MCSa group (P < 0.05), especially in terms of functional recovery. CONCLUSIONS: MCS seems to have a beneficial effect after peripheral nerve injury and repair in terms of nerve regeneration and muscle reinnervation, especially when acute mode is used.

Radiofrequency ablation of spinal osteoid osteoma: a prospective study.

OBJECTIVE Surgery has been considered the standard treatment for spinal osteoid osteomas that are refractory to analgesic agents. Radiofrequency ablation (RFA) is a less invasive technique with established efficiency for the treatment of peripheral osteoid osteomas. The main objectives of this study are to evaluate the safety of RFA based on the results of a previous experimental study in rats conducted in the authors' laboratory and to identify its short- and long-term efficiency in the treatment of spinal osteoid osteomas. METHODS Between March 2009 and July 2016, 8 consecutive patients with spinal osteoid osteomas were enrolled in the study and underwent 9 CT-guided RFA procedures. All patients presented with spinal pain (median preoperative visual analog scale [VAS] score 7.55, range 6-8.8) predominantly during the night, and they all had normal neurological examination results before the procedure. Pain (according to the VAS score) and neurological status were reassessed immediately before discharge, with further follow-up at 1, 6, and 12 months after the procedure. At the final follow-up, VAS score, neurological examination, patient satisfaction, and a radiological control (CT scan) were documented (median 48 months, range 12-84 months). VAS scores before and after the procedure were compared during the 3 days before surgery (D0), on the day of the surgery, Day 1 (D1), and at the final follow-up. RESULTS No neurological deficit was documented following the procedure or at the final follow-up. A statistically significant reduction in the VAS score was observed on Day 1 (mean 2.56 ± 0.68, p = 0.005) compared with D0. At the final follow-up, all patients reported a VAS score of 0 and a satisfaction rate of 100%. Only 1 patient had recurrent symptoms (pain, VAS score 8.1) 6 months after the initial RFA. A second procedure was performed, and the patient was subsequently symptom free at the final follow-up. CT scanning performed in all patients (12-84 months post-RFA) showed residual sclerosis in 4 patients and complete resolution of the radiological lesion in the remaining 4 patients. CONCLUSIONS CT-guided RFA appears to be a safe and effective method for the management of spinal osteoid osteoma and can be safely performed for lesions close to the dura or exiting nerve root based on the motor response threshold testing performed during the procedure. It should be considered the treatment of choice for spinal osteoid osteomas refractory to conservative treatment, thus avoiding more aggressive spinal approaches with subsequent potential morbidity.

Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain: Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review.

BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide the neuromodulation society worldwide into "believers" and "nonbelievers." A European expert meeting was organized in Brussels, Belgium by the Benelux Neuromodulation Society in order to develop uniform MCS protocols in the preoperative, intraoperative, and postoperative courses. METHODS: An expert meeting was organized, and a questionnaire was sent out to all the invited participants before this expert meeting. An extensive literature research was conducted in order to enrich the results. RESULTS: Topics that were addressed during the expert meeting were 1) inclusion and exclusion criteria, 2) targeting and methods of stimulation, 3) effects of MCS, and 4) results from the questionnaire. CONCLUSIONS: Substantial commonalities but also important methodologic divergencies emerged from the discussion of MCS experts from 7 European Centers. From this meeting and questionnaire, all participants concluded that there is a need for more homogenous standardized protocols for MCS regarding patient selection, implantation procedure, stimulation parameters, and follow-up-course.

On the relation between sensory deafferentation, pain and thalamic activity in Wallenberg's syndrome: a PET-scan study before and after motor cortex stimulation.

Decrease of thalamic blood flow contralateral to neuropathic pain has been described by several groups, but its relation with sensory deafferentation remains unclear. Here we report one instance where the thalamic effects of sensory deafferentation could be dissociated from those of neuropathic pain. A 50-year-old patient underwent a left medullary infarct leading to right-sided thermal and pain hypaesthesia up to the third right trigeminal division, as well as in the left face. During the following months the patient developed neuropathic pain limited to the left side of the face. Although the territory with sensory loss was much wider in the right (non painful) than in the left (painful) side of the body, PET-scan demonstrated significant reduction of blood flow in the right thalamus (contralateral to the small painful area) relative to its homologous region. After 3 months of right motor cortex stimulation the patient reported 60% relief of his left facial pain, and a new PET-scan showed correction of the thalamic asymmetry. We conclude that thalamic PET-scan hypoactivity contralateral to neuropathic pain does not merely reflect deafferentation, but appears related to the pain pathophysiology, and may be normalized in parallel with pain relief. The possible mechanisms linking thalamic hypoactivity and pain are discussed in relation with findings in epileptic patients, possible compensation phenomena and bursting thalamic discharges described in animals and humans. Restoration of thalamic activity in neuropathic pain might represent one important condition to obtain successful relief by analgesic procedures, including cortical neurostimulation.

Long-term functional results of selective peripheral neurotomy for the treatment of spastic upper limb: prospective study in 31 patients.

OBJECT: To manage refractory upper-limb spasticity, selective peripheral neurotomy (SPN) is proposed when the spastic muscles to be treated are under the control of a single or a few peripheral nerves. The aim of this study was to assess prospectively the long-term effects of SPN. METHODS: Thirty-one patients with disabling upper-limb spasticity were selected by a multidisciplinary team using clinical, analytical, and functional scales as well as nerve block tests for assessment. Sixty-four SPNs were performed at the level of the musculocutaneous (15 SPNs), the median (25 SPNs), and the ulnar (24 SPNs) nerves. Results of a long-term follow up (mean 4.5 years) showed statistically significant improvement on 1) analytical assessment (p < 0.01): resting position, active amplitude, and motor strength; 2) Ashworth Scale scoring (p < 0.01); 3) hand function assessment (p < 0.01); and 4) rating of daily activities. Four patients with severe painful spasticity experienced complete pain relief after surgery. On the basis of a Visual Analog Scale ranging from 0 to 100, the mean degree of patient satisfaction was 61.5. Complications occurred in five patients (15%): two postoperative hematomas, one (temporary) hypesthesia, and one transient paresia of the wrist and finger flexors. CONCLUSIONS: Selective peripheral neurotomy leads to long-term satisfactory improvement in function and/or comfort with a low morbidity rate in appropriately selected patients suffering from severe harmful spasticity of the upper limb that has been refractory to conservative therapy. Patients must be selected after complete assessment by a multidisciplinary team.

Antithrombotic Medication Use and Misuse Among Patients with Intracranial Hemorrhage: A 16-Year, Lebanese, Single-Center Experience.

OBJECTIVE/BACKGROUND: The use of antithrombotic medication (ATM) frequently is reported in patients with intracranial hemorrhage (ICH) and is associated with increased mortality. Unfortunately, ATMs sometimes are prescribed and/or used inappropriately. We sought to determine the rate of ATM misprescription/misuse among patients with ICH in a single-center retrospective study. METHODS: All patients admitted with ATM-related ICH in 1998-2014 were included. Charts were reviewed and demographic, clinical, and radiologic variables were recorded. The type of ATM, dose, and duration of treatment were analyzed critically. The adequacy of ATM prescription/use was assessed in light of the recommendations and guidelines of the American Heart Association, American Stroke Association, and French National Authority for Health, in effect at the time of admission. RESULTS: A total of 106 patients with mean age 68 years were identified. Aspirin (53.8%) was the most commonly used drug, followed by oral anticoagulants (31.1%) and clopidogrel (22.6%). In only 80 patients (75.5%), the use of ATM was in line with contemporary guidelines. In the remaining 26 (24.5%), the use of ATMs was inappropriate, including bad drug combination, wrong dose, poor indication, wrong drug class, and/or incorrect treatment duration. CONCLUSIONS: In this Lebanese cohort of patients with ICH, the 24.5% rate of ATM misprescription and/or misuse is highly alarming and the origin of this problem is likely multifactorial. Immediate measures should be undertaken, and efforts should be focused on regaining tight control of ATM prescription and fulfillment, ensuring good patient education, and offering more vigilant oversight on physician licensure.

Thalamic thermo-algesic transmission: ventral posterior (VP) complex versus VMpo in the light of a thalamic infarct with central pain.

The respective roles of the ventral posterior complex (VP) and of the more recently described VMpo (posterior part of the ventral medial nucleus) as thalamic relays for pain and temperature pathways have recently been the subject of controversy. Data we obtained in one patient after a limited left thalamic infarct bring some new insights into this debate. This patient presented sudden right-sided hypesthesia for both lemniscal (touch, vibration, joint position) and spinothalamic (pain and temperature) modalities. He subsequently developed right-sided central pain with allodynia. Projection of 3D magnetic resonance images onto a human thalamic atlas revealed a lesion involving the anterior two thirds of the ventral posterior lateral nucleus (VPL) and, to a lesser extent, the ventral posterior medial (VPM) and inferior (VPI) nuclei. Conversely, the lesion did not extend posterior and ventral enough to concern the putative location of the spinothalamic-afferented nucleus VMpo. Neurophysiological studies showed a marked reduction (67%) of cortical responses depending on dorsal column-lemniscal transmission, while spinothalamic-specific, CO2-laser induced cortical responses were only moderately attenuated (33%). Our results show that the VP is definitely involved in thermo-algesic transmission in man, and that its selective lesion can lead to central pain. However, results also suggest that much of the spino-thalamo-cortical volley elicited by painful heat stimuli does not transit through VP, supporting the hypothesis that a non-VP locus lying more posteriorly in the human thalamus is important for thermo-algesic transmission.

Brain opioid receptor density predicts motor cortex stimulation efficacy for chronic pain.

The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using (11)C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. All patients underwent 2 preoperative baseline scans at 2-wk intervals and were clinically assessed after 7mo of chronic MCS. The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.