Gamma Knife Central Lateral Thalamotomy for Chronic Neuropathic Pain: A Single-Center, Retrospective Study.

BACKGROUND: Chronic neuropathic pain can be severely disabling and is difficult to treat. The medial thalamus is believed to be involved in the processing of the affective-motivational dimension of pain, and lesioning of the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a target for stereotactic lesioning. OBJECTIVE: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain. METHODS: We retrospectively reviewed all patients with neuropathic pain who underwent central lateral thalamotomy using GKRS. We report on patient outcomes, including changes in pain scores using the Numeric Pain Rating Scale and Barrow Neurological Institute pain intensity score, and adverse events. RESULTS: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Meaningful pain reduction occurred in 12 patients (57%) after a median period of 3 months and persisted in 7 patients (33%) at the last follow-up (the median follow-up was 28 months). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared with all other patients (P = .009). No patient had treatment-related adverse events. CONCLUSION: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction after this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.

Stimulation of the medial plantar nerve for complex regional pain syndrome.

We describe a 47-year old male with complex regional pain syndrome II in the distribution of the medial plantar nerve following metatarsal fracture, which was treated with peripheral nerve stimulation. Using a new technique of nerve stimulation with a percutaneous-type electrode, the patient experienced sustained relief at 12 months follow-up. To our knowledge, this is the first report of peripheral neurostimulation effectively managing pain for the medial plantar nerve.

Peripheral median nerve stimulation for the treatment of iatrogenic complex regional pain syndrome (CRPS) type II after carpal tunnel surgery.

We report on the use and follow-up of direct peripheral nerve stimulation of the median nerve for the treatment of iatrogenic complex regional pain syndrome (CRPS). A 56-year-old woman presented with CRPS type II in the right forearm and hand, which had started after multiple carpal tunnel surgeries and had lasted for 2 years. The visual analogue scale (VAS) score was 8-10 out of 10. After a successful 15-day trial of median nerve peripheral nerve stimulation via a quadripolar lead in the right carpal tunnel space, an implantable pulse generator was inserted in the right infraclavicular space. The VAS score decreased to 1-2 out of 10 and the patient regained the ability to sleep. After 36 months of follow-up, the patient was still experiencing good pain relief without other treatment. We conclude that peripheral nerve stimulation is easy to use in pain management and could offer a valid treatment option for iatrogenic CRPS type II.

Maladaptive homeostatic plasticity in a rodent model of central pain syndrome: thalamic hyperexcitability after spinothalamic tract lesions.

Central pain syndrome (CPS) is defined as pain associated with a lesion of the CNS and is a common consequence of spinal cord injuries. We generated a rodent model of CPS by making unilateral electrolytic or demyelinating lesions centered on the spinothalamic tract in rats. Thermal hyperalgesia and mechanical allodynia occurred in both hind paws and forepaws by 7 d postlesion and were maintained >31 d. Field potentials in the ventral posterior lateral nucleus (VPL) in thalamic brain slices from lesioned animals displayed an increased probability of burst responses. Ethosuximide, a T-type calcium channel blocker, eliminated busting in lesioned thalamic slices and attenuated lesion-induced hyperalgesia and allodynia. We conclude that CPS in this model results from an increase in the excitability of thalamic nuclei that have lost normal ascending inputs as the result of a spinal cord injury and suggest that ethosuximide will relieve human CPS by restoring normal thalamic excitability.

Mirror visual feedback alleviates deafferentation pain, depending on qualitative aspects of the pain: a preliminary report.

OBJECTIVES: Following lesions in somatosensory pathways, deafferentation pain often occurs. Patients report that the pain is qualitatively complex, and its treatment can be difficult. Mirror visual feedback (MVF) treatment can improve deafferentation pain. We sought to classify the qualities of the pain in order to examine whether the potential analgesic effect of MVF depends on these qualities. METHODS: Twenty-two patients with phantom limb pain, or pain related to spinal cord or nerve injury, performed a single MVF procedure. Before and after the MVF procedure, we evaluated phantom limb awareness, movement representation of the phantom or affected/paralysed limb, pain intensity on an 11-point numerical rating scale (0-10) and the qualities of the pain [skin surface-mediated (superficial pain) vs deep tissue-mediated (deep pain)] using lists of pain descriptors for each of the two categories. RESULTS: Fifteen of the patients perceived the willed visuomotor imagery of the phantom or affected/paralysed limb after the MVF procedure. In most of the patients, a reduction in pain intensity and a decrease in the reporting of deep-pain descriptors were linked to the emergence of willed visuomotor imagery. CONCLUSIONS: In this pilot study, we roughly classified the pain descriptor items into two types for evaluating the qualities of deafferentation pain. We found that visually induced motor imagery by MVF was more effective for reducing deep pain than superficial pain. This suggests that the analgesic effect of MVF treatment does depend on the qualities of the pain. Further research will be required to confirm that this effect is a specific consequence of MVF.

Mirror therapy in patients with causalgia (complex regional pain syndrome type II) following peripheral nerve injury: two cases.

OBJECTIVE: To describe the use of mirror therapy in 2 patients with complex regional pain syndrome type II following traumatic nerve injury. DESIGN: Two case reports. SUBJECTS: Two patients with complex regional pain syndrome type II. METHODS: Two patients received mirror therapy with the painful hand hidden behind the mirror while the non-painful hand was positioned so that, from the perspective of the patient, the reflection of this hand was "superimposed" on the painful hand. Pain was measured with a visual analogue scale. RESULTS: The first case had developed a severe burning and constant pain in the hand due to a neuroma. In this patient, a strong reduction in pain was found during and immediately after mirror therapy. As a result, the patient was able to perform active exercises that were previously too painful. However, despite the pain relief during and directly after the exercises, the overall level of pain did not decrease. The second patient also had severe burning pain following a glass injury. In this patient, repeated mirror therapy for a 3-month period strongly decreased pain due to causalgia. CONCLUSION: The presented cases demonstrate that the use of mirror therapy in patients with causalgia related to a neuroma is worthy of further exploration as a potential treatment modality in patients with causalgia.

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.

An fMRI study of cortical representation of mechanical allodynia in patients with neuropathic pain.

OBJECTIVE: To investigate cerebral activity associated with allodynia in patients with neuropathic pain. METHODS: The brain responses of 27 patients with peripheral (5), spinal (3), brainstem (4), thalamic (5), lenticular (5), or cortical (5) lesions were studied with fMRI as innocuous mechanical stimuli were addressed to either the allodynic territory or the homologous contralateral region. RESULTS: When applied to the normal side, brush and cold rubbing stimuli did not evoke pain and activated a somatosensory "control" network including contralateral primary (SI) and secondary (SII) somatosensory cortices and insular regions. The same stimuli became severely painful when applied to the allodynic side and activated regions in the contralateral hemisphere that mirrored the "control" network, with, however, lesser activation of the SII and insular cortices. Increased activation volumes were found in contralateral SI and primary motor cortex (MI). Whereas ipsilateral responses appeared very small and restricted after control stimuli, they represented the most salient effect of allodynia and were observed mainly in the ipsilateral parietal operculum (SII), SI, and insula. Allodynic stimuli also recruited additional responses in motor/premotor areas (MI, supplementary motor area), in regions involved in spatial attention (posterior parietal cortices), and in regions linking attention and motor control (mid-anterior cingulate cortex). CONCLUSION: On a background of deafferentation in the hemisphere contralateral to stimuli, enhanced or additional responses to innocuous stimuli in the ipsilateral hemisphere may contribute to the shift of perception from innocuous toward painful and ill-defined sensations.

The amelioration of symptoms in cervical spinal stenosis with spinal cord deformation through specific chiropractic manipulation: a case report with long-term follow-up.

OBJECTIVE: To describe the chiropractic management of a patient with paresthesia on the entire left side of her body and magnetic resonance imaging (MRI)-documented cervical spinal cord deformation secondary to cervical spinal stenosis. CLINICAL FEATURES: A 70-year-old special education teacher had neck pain, headaches, and burning paresthesia on the entire left side of her body. These symptoms developed within hours of being injured in a side-impact motor vehicle accident. Prior to her visit, she had been misdiagnosed with a cerebrovascular accident. INTERVENTION AND OUTCOMES: Additional diagnostic studies revealed that the patient was suffering from cervical spinal stenosis with spinal cord deformation. Two manipulative technique systems (Advanced Biostructural Therapy and Atlas Coccygeal Technique) unique to the chiropractic profession and based on the theory of relief of adverse mechanical neural tension were administered to the patient. This intervention provided complete relief of the patient's complaints. The patient remained symptom-free at long-term follow-up, 1 year postaccident. CONCLUSION: There is a paucity of published reports describing the treatment of cervical spinal stenosis through manipulative methods. Existing reports of the manipulative management of cervical spondylosis suggest that traditional manual therapy is ineffective or even contraindicated. This case reports the excellent short-term and long-term response of a 70-year-old patient with MRI-documented cervical spinal stenosis and spinal cord deformation to less traditional, uniquely chiropractic manipulative techniques. This appears to be the first case (reported in the indexed literature) that describes the successful amelioration of the symptoms of cervical spinal stenosis through chiropractic manipulation. More research into the less traditional chiropractic systems of spinal manipulation should be undertaken.

Complex regional pain syndrome in pediatric patients with severe factor VIII deficiency.

Two boys with severe factor VIII deficiency that initially presented with acute onset of joint pain and swelling consistent with an uncomplicated hemarthrosis are reported. When appropriate management failed to provide resolution of symptoms, alternate diagnoses were considered. Both boys ultimately had complex regional pain syndrome (CRPS) diagnosed. The delay in diagnosis contributed to prolonged patient discomfort and lack of appropriate therapy. Complex regional pain syndrome encompasses a group of disorders that are characterized by pain severity or duration disproportionate to that expected. It is uncommon in the pediatric population. Because early diagnosis and appropriate treatment may improve outcome, it is important for practitioners to consider CRPS in the differential diagnosis of persistent pain in children with hemophilia.

Management of spasticity, pain, and paroxysmal phenomena in multiple sclerosis.

Multiple sclerosis (MS) is a disease with tremendous variability and innumerable symptoms. Among the more common symptoms is spasticity. Despite a lack of full knowledge of the physiology causing this phenomenon, successful treatments have been developed. Many of these have had a recent introduction. Pain and paroxysmal phenomena are surprisingly common in MS, but have not had the recognition their frequency deserves. It is not unusual to hear that they are rare in MS, but surprisingly they are all too common. Their management is changing as newer treatments are developed.

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

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

Complex regional pain syndrome (reflex sympathetic dystrophy and causalgia): management with the calcium channel blocker nifedipine and/or the alpha-sympathetic blocker phenoxybenzamine in 59 patients.

Complex Regional Pain Syndrome (CRPS) is the new name for entities formerly known mostly as Reflex Sympathetic Dystrophy and Causalgia. Treatment of CRPS with either the calcium channel blocker nifedipine or the alpha-sympathetic blocker phenoxybenzamine was assessed in 59 patients, 12 with early stages of CRPS, 47 with chronic stage CRPS. In the early stage CRPS patients, 3 of 5 were cured with nifedipine and 8 of 9 (2 of whom had earlier received nifedipine) with phenoxybenzamine, for a cure rate of 92% (11 out of 12). In the chronic stage CRPS patients, 10 of 30 were cured with nifedipine; phenoxybenzamine cured 7 of 17 patients when administered as a first choice and another 2 of 7 patients who received nifedipine earlier, for a total late stage success rate of 40% (19 out of 47). The most common side effects necessitating discontinuing the drug were headaches for nifedipine and orthostatic dizziness, nausea and diarrhoea for phenoxybenzamine. All male patients on phenoxybenzamine experienced impotence, but this did not lead to discontinuing this agent and immediately disappeared after stopping the drug. These results once again stress the importance of early recognition of CRPS, and treatment with either of these drugs could be considered as a first choice for early CRPS, especially because in this series this treatment was not combined with physical therapy making it very cost-effective. In the chronic stage of CRPS, treatment with these drugs was much less successful (40%), even though it was always combined with physical therapy, but it can still be considered, either as a first choice or when other types of treatment have failed.

Pain clinic #15. Treatment of sciatic nerve causalgia following pelvic fracture.

Direct injury to the sciatic nerve may occur in patients who sustain acetabular/pelvic fractures. Sciatic nerve causalgia has been noted in patients who suffer posterior wall acetabular fracture with or without ipsilateral hip dislocation. Sympathetic nervous system dysfunction is considered the primary cause for this syndrome, although some investigators suggest central nervous system involvement. This report documents the treatment results of three patients suffering from sciatic nerve causalgia who were referred to the Pain Treatment Center during the past year. In each case, diagnosis was confirmed by sympathetic blockade. Treatment regimens varied and included nerve blocks, cryoanalgesia techniques, and transcutaneous electrical nerve stimulation therapy. The syndrome was relieved in these patients within four to six weeks. Patients were followed for six months after initial treatment.

Management of causalgia after peripheral nerve injury.

The authors report on a series of patients with severely painful disorders of peripheral nerves--they review the modern theories on the nature of causalgia and reflex sympathetic dystrophy. Peripheral causes include spontaneous discharges from neuroma sprouts, their sensitivity to adrenergic compounds, ectopic generator activity in abnormally myelinated fires and increased firing in dorsal root ganglia. Central causes include spontaneous activity of deafferented nerves in the dorsal horn and development of response to new receptive fields. The natural history of such disorders is poor--many patients suffering pain for 10 years or more--the clinical picture is characterized by spontaneous burning pain and allodynia and hyperpathia, chronicity, osteoporosis, skin and nail changes and deformities. The basis of treatment is sympathetic blockade using intravenous guanethedine on alternate days. At least 6 blocks are given as the majority of patients do not respond until the 5th or 6th block. Each block is followed by desensitization and intensive rehabilitation. The authors emphasize that sympathetic blockade is only one, albeit the most important, modality in a multi-faceted treatment programme. Surgical attempts to relieve pain almost uniformly failed--causing as they do further neuronal changes peripherally and centrally. Recurrences depend on the degree of initial response. Those who obtained virtually complete relief of pain had a lower recurrence rate but a high proportion needed repeated sessions of treatment at yearly intervals. Follow-ups must therefore be indefinite.

A hypothesis on the physiological basis for causalgia and related pains.

A hypothesis is presented concerning the neuronal mechanisms which subserve the sympathetically maintained pains such as causalgia and reflex sympathetic dystrophy. The hypothesis rests on two assumptions: that a high rate of firing in spinal wide-dynamic-range (WDR) or multireceptive neurons results in painful sensations; and that nociceptor responses associated with trauma can produce long-term sensitization of WDR neurons. The hypothesis states that chronic sympathetically maintained pains are mediated by activity in low-threshold, myelinated mechanoreceptors, that this afferent activity results from sympathetic efferent actions upon the receptors or upon afferent fibers ending in a neuroma and that these afferent fibers evoke sufficient activity in sensitized spinal WDR neurons to produce a painful sensation. This hypothesis is based on known characteristics of these neuronal populations studied in experimental animals and on the observed sensory disturbances reported in patients successfully treated with sympathetic blocks. This hypothesis does not require nerve injury or dystrophic tissue. It explains both the continuous pain and the allodynia that are common to these syndromes and their abolition by sympathetic block. Specific changes are proposed in the diagnosis and treatment of post-traumatic pains.

Deafferentation and causalgia.

The concept of deafferentation pain has been developed as an entity distinct from somatic pain which can arise in the course of both cancerous and nonmalignant disease. Its distinctive clinical features and responses to diagnostic and therapeutic manipulations have been reviewed. Evidence is marshalled to show that it results from gradually developing alterations in the central nervous system, which, once established, persist despite removal of the original stimulus. Evidence is presented that the mesencephalic tegmentum may be part of a reticulothalamocortical system undergoing denervation hypersensitivity following deafferentation, whose stimulation by electric impulses, and, presumably, naturally occurring neural inputs, can result in a painful conscious experience reproducing the patient's pain in a manner similar to that whereby stimulation of temporal-parietal association cortex elicits recall of past events.