Microglial deactivation by adeno-associated virus expressing small-hairpin GCH1 has protective effects against neuropathic pain development in a spinothalamic tract-lesion model.

AIMS: Neuropathic pain after spinal cord injury is one of the most difficult clinical problems after the loss of mobility, and pharmacological or neuromodulation therapy showed limited efficacy. In this study, we examine the possibility of pain modulation by a recombinant adeno-associated virus (rAAV) encoding small-hairpin RNA against GCH1 (rAAV-shGCH1) in a spinal cord injury model in which neuropathic pain was induced by a spinothalamic tract (STT) lesion. METHODS: Micro-electric lesioning was used to damage the left STT in rats (n = 32), and either rAAV-shGCH1 (n = 19) or rAAV control (n = 6) was injected into the dorsal horn of the rats at the same time. On postoperative days 3, 7, and 14, we evaluated neuropathic pain using a behavioral test and microglial activation by immunohistochemical staining. RESULTS: A pain modulation effect of shGCH1 was observed from postoperative days 3 to 14. The mechanical withdrawal threshold was 13.0 ± 0.95 in the shGCH1 group, 4.3 ± 1.37 in the control group, and 3.49 ± 0.85 in sham on postoperative day 3 (p < 0.0001) and continued to postoperative day 14 (shGCH1 vs. control: 11.4 ± 1.1 vs. 2.05 ± 0.60, p < 0.001 and shGCH1 vs. sham: 11.4 ± 1.1 vs. 1.43 ± 0.54, p < 0.001). Immunohistochemical staining of the spinal cord dorsal horn showed deactivation of microglia in the shGCH1 group without any change of delayed pattern of astrocyte activation as in STT model. CONCLUSIONS: Neuropathic pain after spinal cord injury can be modulated bilaterally by deactivating microglial activation after a unilateral injection of rAAV-shGCH1 into the dorsal horn of a STT lesion spinal cord pain model. This new attempt would be another therapeutic approach for NP after SCI, which once happens; there is no clear curative options still now.

Mesencephalotomy, How I Do It: Analysis of 34 Cases

The present paper aims to demystify the use of rostral mesencephalic reticulotomy (mesencephalotomy) in the treatment of chronic pain in cancer patients. A retrospective review of the medical records from the Central Pain and Stereotaxy Department of the A. C. Camargo Cancer Center, São Paulo, state of São Paulo, Brazil, between 2005 and 2012, was performed. Surgical indication was restricted to patients with cancer pain refractory to etiological and symptomatic treatments, > 2 months of expected survival, preserved cognition, and absence of coagulation disorders, of systemic infection, and of intracranial hypertension. We have selected 34 patients, with an average follow-up of 9.4 months, an average age of 54.3 years-old, and an average follow-up time until death of 6.4 months. Lung cancer was themost frequent diagnosis. Satisfactory and immediate pain relief was achieved in 91% of the cases, and 83% of these patients had no relapses. Among the complications, ocular movement disorder was the most frequent, but often transient. Permanent disturbances occurred in 8.8% of the cases (diplopia, rubral tremor, and paresthesia). Compared to the pharmacological treatment, mesencephalotomy was economically feasible, more effective, and improved quality of life. According to the data presented, it can be concluded that mesencephalotomy is a viable procedure for cancer pain control in selected cases.

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

Treatment of medically refractory cancer pain with a combination of intrathecal neuromodulation and neurosurgical ablation: case series and literature review.

OBJECTIVE: Up to 90% of patients with advanced cancer experience intractable pain. For these patients, oral analgesics are the mainstay of therapy, often augmented with intrathecal drug delivery. Neurosurgical ablative procedures have become less commonly used, though their efficacy has been well-established. Unfortunately, little is known about the safety of ablation in the context of previous neuromodulation. Therefore, the aim of this study is to present the results from a case series in which patients were treated successfully with a combination of intrathecal neuromodulation and neurosurgical ablation. DESIGN: Retrospective case series and literature review. SETTING: Three institutions with active cancer pain management programs in the United States. METHODS: All patients who underwent both neuroablative and neuromodulatory procedures for cancer pain were surveyed using the visual analog scale prior to the first procedure, before and after a second procedure, and at long-term follow-up. Based on initial and subsequent presentation, patients underwent intrathecal morphine pump placement, cordotomy, or midline myelotomy. RESULTS: Five patients (2 male, 3 female) with medically intractable pain (initial VAS = 10) were included in the series. Four subjects were initially treated with intrathecal analgesic neuromodulation, and 1 with midline myelotomy. Each patient experienced recurrence of pain (VAS ≥ 9) following the initial procedure, and was therefore treated with another modality (intrathecal, N = 1; midline myelotomy, N = 1; percutaneous radiofrequency cordotomy, N = 3), with significant long-term benefit (VAS 1-7). CONCLUSION: In cancer patients with medically intractable pain, intrathecal neuromodulation and neurosurgical ablation together may allow for more effective control of cancer pain.

Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.

BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. RESULTS: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. CONCLUSIONS: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.

Evidence for the involvement of the spinoparabrachial pathway, but not the spinothalamic tract or post-synaptic dorsal column, in acute bone nociception.

We have previously reported that acute noxious mechanical stimulation of bone activates neurons throughout the dorsal horn of the lumbar spinal cord, and argued that the spinal mechanisms that mediate bone nociception are different to those that mediate cutaneous and visceral nociception. In the present study, we provide evidence that the ascending spinal pathways that mediate acute bone nociception also differ to those that mediate acute cutaneous and visceral nociception. Injections of a retrograde tracer (Fluorogold) were made into the thalamus, gracile nucleus or lateral parabrachial nucleus to identify spinothalamic, post-synaptic dorsal column or spinoparabrachial projection neurons respectively (n=4 in each group). Spinal dorsal horn neurons activated by acute noxious mechanical stimulation of bone (bone drilling) were identified in these animals using Fos immunohistochemistry. Fluorogold and Fos-like immunoreactivity was not colocalized in any dorsal horn neurons projecting to the thalamus or gracile nucleus. In contrast, a total of 12.2+/-1.1% (mean+/-S.E.M.) of the spinoparabrachial projection neurons contained Fos-like immunoreactive nuclei following bone drilling and this was significantly greater than the percentage (3.4+/-0.5%) in animals of a sham surgery group (n=4) that were not exposed to bone drilling (Mann-Whitney; p<0.05). These data provide evidence for the involvement of the spinoparabrachial pathway, but not the spinothalamic or post-synaptic dorsal column pathways, in the relay of information regarding acute noxious mechanical stimuli applied to bone, and suggest that spinal pathways that mediate acute bone nociception may be different to those that mediate acute nociception of cutaneous and visceral origin.

Bilateral high-level percutaneous cervical cordotomy in cancer pain due to lung cancer: a case report.

BACKGROUND: Computed tomography-guided high-level percutaneous cordotomy has been used unilaterally or bilaterally for the treatment of localized intractable pain in malignancies. CASE DESCRIPTION: A 57-year-old man was admitted to the hospital with the complaint of intractable pain involving the left side of the chest, axillary region, and shoulder. He was operated for small cell lung cancer on the left side in December 2003 and received radiotherapy and chemotherapy. His neurological examination was normal. Magnetic resonance imaging of the thorax revealed contrast-enhancing lesions on the left side extending to mediastinum and pleura. His pain was relieved completely after the first cordotomy procedure, and he was discharged from the hospital on the second postoperative day. The patient was readmitted to the hospital with the complaint of severe unilateral chest pain like the initial pain on the right side 4 days after cordotomy. The CT-guided bilateral high-level percutaneous cordotomy was performed with a 15-day interval. CONCLUSION: The CT-guided bilateral high-level percutaneous cordotomy can be used in the treatment of intractable upper trunk pain in patients with cancer without pulmonary dysfunction.

[Clinico-urodynamic correlation in the hereditary ataxias]. / Correlación clínico-urodinámica en las ataxias hereditarias.

OBJECTIVES: To evaluate lower urinary tract functional symptoms in a series of patients with ataxia and to determine by urodynamic studies the kind of bladder-urethra neurological dysfunction in each case. We posed the question if the clinical picture could be enough to establish the diagnosis and therapeutic management of these patients with hereditary ataxia, or on the contrary it would be necessary to perform urodynamic studies in all cases. METHODS: Due to the low incidence of hereditary ataxias and patients' mobility it was necessary to recruit patients from various hospitals. The urodynamic study protocol employed in this study included 1) Evaluation of urinary symptoms; 2) Neurological physical examination; 3) Flowmetry with post void residual; 4) Cystomanometry; and 5) Perineal electromyography. We analyzed the relationship between urinary symptoms and urodynamic diagnosis, considering variables such as age, gender, type of ataxia, and time of evolution of the disease. RESULTS: The series includes 34 patients with ataxia and urinary symptoms, 14 cases of Friedreich's ataxia (FA) (41.2%) and other 20 cases of other various forms of ataxia we name non-Friedreich's (NF) (58.8%). Mean age was 37.2 years in FA and 50 years in NF (p < 0.05). Mean time of disease evolution was 20.5 yr. for FA, and 14.9 yr. for NF ataxia (p < 0.1). A mixed urinary syndrome was predominant in 53% of the patients, and 41.1% presented pure irritative symptoms in relation to voiding urgency (85.2%). The most frequent urodynamic diagnosis was detrusor hyperreflexia (61.7%) (37.5% with dyssynergia), followed by areflexia (or hyporeflexia) (23.5%), and normal studies (14.7%). Detrusor hyperreflexia presented with irritative urinary symptoms in 85.7% of the patients, and areflexia or hyporeflexia presented with obstructive symptoms in 75% of the cases. CONCLUSION: Although there is a good clinical-urodynamic correlation in cases of ataxia, we consider it is necessary to perform a complete urodynamic study in males with hereditary ataxia in order to rule out bladder outlet obstruction due to BPH. On the other hand, due to the fact that progression of the lesions can modify the clinical picture of the patient (including urinary tract symptoms), we consider essential to re-evaluate ataxic patients periodically to adapt their treatment to the urodynamic diagnosis.

Intrapericardiac injections of algogenic chemicals excite primate C1-C2 spinothalamic tract neurons.

Extracellular potentials of 38 C1-C2 spinothalamic tract (STT) neurons in anesthetized monkeys (Macaca fascicularis) were examined for responses to intrapericardiac injections of an algogenic chemical mixture (adenosine, 10(-3) M; bradykinin, prostaglandin E(2), serotonin, histamine, each 10(-5) M). Chemical stimulation of cardiac/pericardiac receptors increased activity of 21 cells, decreased activity of 5 cells, and did not change activity of 12 cells. Cells excited by chemical stimuli received input from noxious mechanical stimulation of somatic fields; most receptive fields included the neck, inferior jaw, or head areas. Nerve ablations in 11 cells excited by intrapericardiac chemicals showed that cardiac input activated by algogenic chemicals traveled primarily in vagal afferent fibers to C1-C2 segments; phrenic or cardiopulmonary sympathetic inputs were predominant in 2 of 11 cells. These results supported the concept that activation of cardiac vagal afferents might lead to the production of referred pain sensation in somatic fields innervated from high cervical segments.

[Brain stem glioma presenting with contralateral sensory impairment of ascending nature].

A case of brain stem glioma, presenting with impairment of contralateral pain-temperature sense of ascending nature, is reported. A 38-year-old woman with documented neurofibromatosis type 1 (NF-1) was admitted to our hospital for treatment, complaining of diminished pain-temperature sense in the left lower extremity. On admission, the symptom was first evaluated to be due to cervical myelopathy although motor involvement was absent. An MRI, myelography and CT-myelography of the cervical spine were done, demonstrating no abnormality. Shortly after the admission the sensory impairment progressed to the upper chest level and then to the upper extremity on the left. Because of her documented NF-1 a brain CT was checked, revealing a small mass with ring enhancement in the dorsal midbrain on the right. On MRI, the tumor location was at the right dorsolateral tectal region of superficial situation. Under the diagnosis of midbrain glioma the tumor was partially removed by the occipital transtentorial approach. At operation, the tumor has grown intraaxially, having pinkish-gray color and central necrosis. Histologically the tumor was diagnosed as glioblastoma multiforme. Postoperatively she presented a definite improvement of the sensory impairment in the reverse order, that is from upper extremity and then to the lower extremity. Progression and post-treatment improvement of the impaired pain-temperature sense in this case suggested that the topography and lamination of the lateral spinothalamic tract might be present even in the dorsal midbrain, namely the posterior-superficial layer to be sacral segment and the anterior-deep layer to be cervical one.

Understanding central post-stroke pain.

Almost a century ago, two French neurologists described an unusual pain syndrome following stroke. This so-called "thalamic" pain of Dejerine-Roussy exists today, affecting approximately 30,000 survivors of stroke in the United States (US) alone. Lesions involving the neospinothalamocortical tract are thought to cause thalamic pain, but the exact pathogenesis is unclear. Pharmacotherapeutic and surgical approaches offer pain relief in selected patients. Although definitive relief of central post-stroke pain (CPSP) may not be achievable for all at this time, intelligent and informed examination of the full range of options offers every sufferer a real potential for relief and mastery of pain. It is hoped that information provided herein will foster "intelligent caring" and facilitate informed decision making by consumers and caregivers alike.

Thermal and pain sensations evoked by microstimulation in the area of human ventrocaudal nucleus.

1. We have studied the sensations evoked by threshold microstimulation (TMS) in the area of the human principal sensory nucleus of the thalamus [ventralis caudalis (Vc)] in patients (n = 11) undergoing stereotactic surgery for the treatment of movement disorders and pain. Preoperatively, patients were trained to describe somatic sensory stimuli using a standard list of descriptors. This same list was used to describe sensations evoked intraoperatively by thalamic microstimulation. Stimulation sites (n = 216) were defined by location within the area where the majority of cells had a reproducible response to innocuous cutaneous stimulation (core region) or in the cellular area posterior and inferior to the core region (posteroinferior region). 2. TMS-evoked sensations were categorized as paresthetic if the descriptors "tingle," "vibration," or "electric current" were chosen by the patient to describe the sensation and as thermal/pain if the descriptors "cool," "warm," "warm and cool," or "pain" were chosen. Thermal/pain sensations were evoked by stimulation in 82% (9/11) of patients and at 19% of sites studied. These results suggest that thalamic microstimulation can evoke thermal/pain sensations reproducibly across patients. 3. Thermal/pain sensations were evoked more frequently by stimulation at sites in the posteroinferior region (30%) than by stimulation at sites in the core region (5%). Nonpainful thermal sensations composed the majority of thermal/pain sensations evoked by stimulation in both the core (80%) and posteroinferior regions (86%). Sites where stimulation evoked pain and nonpainful cool sensations were found anterior to the area where nonpainful warm sensations were evoked. Thermal/pain sensations were evoked at sites located medially near the border between the core and posteroinferior regions. 4. Radiologic techniques were used to determine the presumed nuclear location of stimulation sites. Thermal/pain sensations were evoked less frequently by stimulation in the part of Vc included in the core region than by stimulation in any of the following: the part of Vc included in the posteroinferior region, ventralis caudalis portae nucleus, ventralis caudalis parvocellularis nucleus, or the white matter underlying the ventral nuclear group. 5. The location of the sensation evoked by stimulation [projected field (PF)] varied widely in size. PFs were categorized as large if they involved more than one part of the body (e.g., face and arm) or if they crossed at least one joint proximal to the metacarpophalangeal joint or to the metatarsophalangeal joint. PFs were more frequently large at sites where thermal/pain sensations were evoked by TMS (33%) than at those where paresthesia were evoked (6%).(ABSTRACT TRUNCATED AT 400 WORDS)

CT-guided percutaneous selective cordotomy.

In this article the technique of CT-Guided Selective Cordotomy is described. The advantages of CT guidance in percutaneous cordotomy are the measurement of spinal cord diameters at the lesion site for each individual patient, direct visualization of target electrode relations, demonstration of spinal cord displacement during the procedure and localization of the electrode system in a specific part of the spinothalamic tract. Local destruction of the spinothalamic tract leads to selective cordotomy. Since 1987, CT-Guided Cordotomy has been applied to 54 cases of intractable cancer pain. In 33 of the 54 cases, the cordotomy was selective enough to be successful with a local denervation of the area where the pain was dominant. Except for one temporary hemiparesis and one temporary ataxia, no complications or side effects were observed.

Stereotactic mesencephalotomy.

Within the mesencephalon lie nuclear masses and fiber tracts that connect higher and lower portions of the neuraxis. The pathways subserving epicritic (discriminatory) sensation and protopathic (motivational) sensation are adjacent to one another and can be localized precisely with stereotaxy. Discrete thermal lesions overflowing between the direct spinothalamic and quintothalamic pathways laterally and the more diffuse ascending pathways medially can be created. By careful target selection the surgeon can avoid significant damage to adjacent structures and offer relief of central or malignant pain without substantial sensory disturbance. At the same time the emotional disturbances that often persist with other remedies are reduced. Intraoperative electrophysiologic monitoring may help minimize unwanted and distressing side effects. It is fortunate that nature has designed the upper brain stem in such a fashion to allow effective pain relief procedures. Although stereotactic mesencephalotomy is not a panacea, it offers relief of pain syndromes that cannot otherwise be helped while abolishing the associated emotional problems that otherwise can be relieved only by psychosurgical procedures.

Thalamic pain and stereotactic mesencephalotomy.

The severe pain that can be experienced by stroke patients is refractory both to drugs and to non-medical therapies. Various surgical procedures are widely advocated for its relief, stereotactic mesencephalic tractotomy in particular providing good results. Twenty seven patients with pain of central origin following stroke underwent stereotactic mesencephalic tractotomy by thermocoagulation at one of two alternative sites. Fourteen had lesions created at the original target adjacent to the superior colliculus, 75% reporting long term relief of their pain. Of this group, 83% had residual postoperative ocular dysfunction (50% symptomatic) and two died soon after surgery. Thirteen patients had surgery at the revised target at the level of the inferior colliculus: 58% had long term pain relief, 23% had ocular problems (none symptomatic) and mortality was nil.

Anatomy, physiology, and neuropharmacology of cancer pain.

The anatomy, physiology, and pharmacology of nociception and its modification by analgesic drugs have been studied extensively in the past decade. Although the neural mechanisms of nociceptors and the stimuli that activate them are much better understood, it must be emphasized that the perception of pain, as well as the meaning of pain to the individual, is a complex behavioral phenomenon and involves psychologic and emotional processes in addition to activation of nociceptive pathways. Pain related to malignant disease can be classified as somatic, visceral, and deafferentation in type. Somatic pain and visceral pain involve direct activation of nociceptors and are often a complication of tumor infiltration of tissues or injury of tissues as a consequence of cancer therapy. The management of this type of pain is typically accomplished by treating the tumor (with surgery, chemotherapy, and/or radiation therapy) and by using the appropriate non-narcotic, narcotic, and adjuvant analgesic agents. Neuroablative therapies may be helpful in specific circumstances. For example, cordotomy may be helpful for unilateral pain below the waist in patients with somatic and visceral pain. This procedure may also be helpful for early deafferentiation pain (i.e., lumbosacral plexopathy) in which peripheral nerves are compressed but not infiltrated or destroyed by metastatic tumor growth. Deafferentiation pain may be a complication of tumor infiltration of peripheral nerve or of cancer therapy that injures neural tissue. This type of pain is often poorly tolerated and difficult to control, particularly if not treated early and aggressively. Although incompletely understood, the pathophysiology of deafferentation pain appears to be different from that of somatic or visceral pain, and the treatment approaches may be different. Management approaches to deafferentation pain usually emphasize treatment of the pain, because injury to the nervous system may be difficult to reverse, even if one can successfully treat the underlying malignancy, and many deafferentation pain syndromes occur as a complication of cancer therapy. The role of narcotic analgesics in the management of deafferentation pain is not clear, although the published experience suggests that they are less useful than in somatic or visceral pain.

Sensory effects in man of lesions of the posterior columns and of some other afferent pathways.

Clinical observations are presented on the sensory effects of lesions of different afferent pathways of the spinal cord, correlated whenever possible with histological evidence of the location and extent of the lesions. They are based on personal cases and on significant cases in the literature, including posterior column section, other causes of damage to the posterior columns, and cases of commissural myelotomy. It is concluded that the traditional view of the effects of lesions of the posterior columns is correct, but that evidence from cases proved by postmortem examination is still needed. When the information normally supplied by the posterior columns is cut off, primary sensibility for light touch and pressure is not lost, but any kind of discrimination is disturbed. There is also a disturbance in knowledge of movement and position, ataxia, and clumsiness in the use of the hands. These defects greatly affect the palpatory examination of objects and, although they may appear slight on routine neurological examination, they can cause severe disturbances in the activities of daily living. For tactile modalities, a lesion of the spinothalamic complex causes minimal or no defects and a lesion of the posterior columns causes only slight defects, whereas a lesion of both pathways gives rise to total loss of tactile and pressure sensibility in the part of the body served by both pathways. This conclusion is based on 2 cases with combined commissural myelotomy and anterolateral cordotomy. The following disturbances of mechanoreception attributed to lesions of the posterior columns are discussed: lability of threshold, persistence of sensation, tactile and postural hallucinations and temporal and spatial disturbances. In man, lesions of the posterior columns cause an increase in pain, tickle, warmth and cold. Cases are presented with and without lesions of the posterolateral columns in conjunction with lesions of one or both anterolateral columns. As these lesions did not affect sensation and as there was no difference in the sensory state following anterolateral cordotomies with or without involvement of the posterolateral column, it is concluded that lesions of this column have no effect on sensation. Cases with lesions of the anterior two-thirds of the cord are also presented to illustrate the sensory state with only the posterior third of the cord intact. In these cases, tactile and pressure sensibility and knowledge of movement and position are normal.

Analgesic levels and technical method in stereotactic pontine spinothalamic tractotomy.

Stereotactic pontine spinothalamic tractotomy was performed on eight patients with severe pain due to malignancy. The procedure enables high levels of analgesia to be obtained with less risk of respiratory and micturition disorders than percutaneous or open cordotomy.

Cerebral-evoked responses elicited by direct stimulation of the lateral spinothalamic tract in the human.

The authors recorded cerebral-evoked responses elicited by direct stimulation of the human lateral spinothalamic tract (LST) during percutaneous cordotomy to investigate central conduction of noxious stimuli. These responses consisted of four negative potentials, peak latency being 3.8 (N1), 8.4 (N2), 12.2 (N3) and 21.9 (N4) ms respectively. N1 showed wide distribution over the scalp and was considered to be of subcortical origin. N2-N4 were distributed in both the temporal and central area. The different distribution pattern of N2-N4 from conventional somatosensory-evoked potential suggested a different projection of LST from the medial lemniscus system.

Loss and recovery of reactivity to noxious stimuli in monkeys with primary spinothalamic cordotomies, followed by secondary and tertiary lesions of other cord sectors.

Cebus albifrons monkeys were trained to escape electrical stimulation of either leg at five intensities, spanning a range from mild tingle to intense but tolerable pain, as judged by human observers who experienced the same stimuli. The average duration of stimulation received by the animals at each intensity was plotted for each leg during the period required for recovery of responsiveness to noxious electrical stimulation following ventrolateral spinal cordotomy. Recovery of escape responding was observed similarly following subsequent lesions to the spinal cord, in an attempt to define the pathways that subserve pain conduction after readjustment from cordotomies that produced substantial deficits of escape behaviour. The most enduring elevations of duration of stimulation by lesion I (left cordotomy) were produced by lesions that involved all of the ventrolateral column and most or all of one or both ventral columns. Secondary lesions of the dorsal columns, Lissauer's tract and the dorsolateral columns, in various combinations, did not produce long-term effects on escape responding. In contrast, a complete ventral hemisection produced a pronounced bilateral deficit that did not recover fully over three hundred and five post-operative days. The major conclusions are: (1) that the dorsal pathways do not play a major role in the rostral conduction of information critical for pain perception in monkeys, even though these pathways receive input from high threshold receptors; and (2) in order to produce a lasting decrease of pain sensitivity in primates by spinal surgery, the lesion must be bilateral and must involve both the ventrolateral and ventral columns.