Electrical stimulation of precentral cortical area in the treatment of central pain: electrophysiological and PET study

The clinical, electrophysiological and haemodynamic effects of precentral gyrus stimulation (PGS) as a treatment of refractory post-stroke pain were studied in 2 patients. The first patient had a right hemibody pain secondary to a left parietal infarct sparing the thalamus, while the second patient had left lower limb pain developed after a right mesencephalic infarct. In both cases, spontaneous pain was associated with hyperpathia, allodynia and hypoaesthesia in the painful territory involving both lemniscal and extra-lemniscal sensory modalities in patient 1, extra-lemniscal sensory modality only in patient 2. Both patients were treated with electrical PGS by means of a 4-pole electrode, the central sulcus being per-operatively located using the phase-reversal of the N20 wave of somatosensory evoked potentials. No sensory side effect, abnormal movement or epileptic seizure were observed during PGS. The analgesic effects were somatotopically distributed according to the localization of electrode on motor cortex. A satisfactory long-lasting pain control (60-70% on visual analog scale) as well as attenuation of nociceptive reflexes were obtained during PGS in the first patient. Pain relief was less marked and only transient (2 months) in patient 2, in spite of a similar operative procedure. In this patient, in whom PGS eventually evoked painful dysethesiae, no attenuation of nociceptive RIII reflex could be evidenced during PGS. Cerebral blood flow (CBF) was studied using emission tomography (PET) with O-labeled water. The sites of CBF increase during PGS were the same in both patients, namely the thalamus ipsilateral to PGS, cingulate gyrus, orbito-frontal cortex and brainstem. CBF increase in brainstem structures was greater and lasted longer in patient 1 while patient 2 showed a greater CBF increase in orbito-frontal and cingular regions. Our results suggest that PGS-induced analgesia is somatotopically mediated and does not require the integrity of somatosensory cortex and lemniscal system. PGS analgesic efficacy may be mainly related to increased synaptic activity in the thalamus and brainstem while changes in cingulate gyrus and orbito-frontal cortex may be rather related to attentional and/or emotional processes. The inhibitory control on pain would involve thalamic and/or brainstem relays on descending pathways down to the spinal cord segments, leading to a depression of nociceptive reflexes. Painful dysesthesiae during stimulation have to be distinguished from other innocuous sensory side effects, since they may compromise PGS efficacy.     

Cancer-related neuropathic pain

Infection by the human immunodeficiency virus (HIV) causes depletion of CD4-positive lymphocytes with consequent immunodeficiency. HIV infection also causes, by direct or indirect mechanisms, both reactive and neoplastic changes in lymphoid tissues. In primary infection reactive changes are a direct response to HIV. Later in the course of the disease there are reactive changes in lymph nodes and extranodal lymphoid tissues which are likely to be largely an indirect effect of HIV infection, being a response to opportunistic infection by other organisms. There is also an increased incidence of autoimmune phenomena in HIV-infected subjects which is likely to be consequent, at least in part, on impaired control of the proliferation of self-reactive B-cell clones. A second mechanism of immune damage of blood cells, probably operating in the case of HIV-related immune thrombocytopenic purpura, is that of cellular damage by immune complexes containing antiviral antibodies. Lymphoid neoplasms associated with HIV infection include non-Hodgkin's lymphoma, Hodgkin's disease and, uncommonly, plasma cell dyscrasias. HIV-associated lymphomas have distinct clinicopathological features and generally a poor prognosis. As for reactive lymphoid lesions, induction of neoplasia is likely, in the majority of cases, to be an indirect rather than a direct effect of the virus. The combination of chronic B-cell stimulation and impaired T-cell function is important, and interaction of lymphoid cells with virus-infected stromal cells may also play a role. Infection by oncogenic viruses such as the Epstein-Barr virus and human herpes virus 8 is also aetiologically important. In rare cases of T-cell lymphoma, HIV may be directly oncogenic.     

The effect of peripheral glycerol on trigeminal neuropathic pain examined by quantitative assessment of abnormal pain and sensory perception

In nine patients with trigeminal neuropathic pain after nerve injury, we examined prospectively the effect of peripheral glycerol neurolysis on abnormal pain and sensory perception. In the painful facial skin area of these patients, we found increased temperature and tactile thresholds and the presence of abnormal temporal summation of pain. In seven patients, neuropathic pain was peripheral and disappeared after application of local anaesthesia at or proximal to the site of nerve injury. Neuropathic pain was central in two patients, and unresponsive to local anaesthesia applied proximal to the site of nerve injury. Six weeks after injection of glycerol proximal to the site of nerve injury, no or marginal pain relief was found in 8 patients with peripheral or central trigeminal neuropathic pain. On the other hand, in one of the patients with peripheral trigeminal neuropathic pain, glycerol was given at the site of nerve injury, and produced total pain relief for the whole observation period of 7 months. In this patient, pain relief was associated with normalisation of abnormal temporal summation of pain, which was not observed in the 8 patients with no or marginal pain relief. No further changes in temperature or tactile thresholds were found in any of the 9 patients after a single injection of absolute glycerol. Total pain relief in one of the patients probably is related to the ability of glycerol to inhibit ongoing ectopic impulse generation at the site of nerve injury. We suggest that glycerol-induced reduction of primary afferent hyperactivity may secondarily result in down-regulation of central neuronal hyperexcitability. The efficacy of application of glycerol at the site of nerve injury in patients with peripheral trigeminal neuropathic pain may warrant further investigation. However, this prospective study does not provide evidence that application of glycerol proximal to the site of nerve injury has a place in the treatment of trigeminal neuropathic pain.     

Pharmacology of neuropathic pain

The development of new animal models now allows the pharmacological study of the neuropathic pain. Our results concern mainly antidepressants and opiates; although the results are incomplete, they show that the different components of the pain syndrome depend on various mechanisms and require adapted treatments and that the treatment must begin as soon as possible, before plastic processes sustain a vicious circle of pain. In the future, pharmacological studies will permit better specification of indications for drugs already used, as well as the associations that improve their efficacy; studies will also encourage development of new treatments more adapted to the physiopathology of the pain syndrome.     

Electrical stimulation of the trigeminal nerve root for the treatment of chronic facial pain

BACKGROUND: Alterations of the p53 gene are involved in the development of diverse human malignancies, but their incidence and clinicopathologic features are still not well characterized for endometrial carcinoma. METHODS: To investigate the clinicopathologic significance of p53, mutations and loss of heterozygosity (LOH) in endometrial carcinoma in 92 patients with this disease were examined. RESULTS: Mutations of p53 were detected in 20 (22%) of the 92 patients with carcinoma, and LOH was detected in 23 (32%) of the 72 patients in whom heterozygosity of the gene was available. There was a significant correlation between the occurrence of mutation and LOH. Mutations and LOH were more frequent in patients with Grade 3 tumors than in those with Grades 1 and 2 tumors (P = 0.0498, P = 0.0051, respectively). Patients with LOH had a poorer postoperative survival than those without LOH (P = 0.0022, log-rank test), and patients with both LOH and mutation showed the worst prognosis (P < 0.0001, log rank test). Loss of heterozygosity of the p53 gene showed a significant relation to prognosis that was independent of tumor stage, histologic grade, and muscular invasion. CONCLUSIONS: Mutation and LOH of the p53 gene are prognostic indicators in patients with endometrial carcinoma, suggesting that alterations of p53 may play an important role in the development of this cancer.     

Drug interactions in human neuropathic pain pharmacotherapy

The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and task persistence of 60 boys with attention deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo design, boys in 4 groups (received placebo/drug crossed with told placebo/drug) completed the task in success and failure conditions. Medication improved participants' task persistence following failure. Participants' task performance was not affected by whether they thought they had received medication or placebo. Children made internal attributions for success and made external attributions for failure, regardless of medication or expectancy. These findings confirm previous reports that it is the pharmacological activity of MPH that affects ADHD children's self-evaluations and persistence. The results contradict anecdotal reports that MPH causes dysfunctional attributions and confirm previous studies showing that medication does not produce adverse effects on the causal attributions of children with ADHD.     

Sternocleidomastoid muscle inhibition induced by trigeminal stimulation

Among numerous reports of anatomical and functional coupling between the trigeminal and cervical systems is the demonstration that the sternocleidomastoid (SCM) muscles may become activated along with the masseter muscles during forceful abrupt biting maneuvers. Whether the co-activated SCM is also inhibited by stimuli that produce masseter inhibition is not known. This study evaluated the SCM for the presence of inhibition during mechanically-elicited (chin or forehead tap) and electrically-elicited (anterior maxillary gingiva stimulation) inhibition of the masseter muscle in ten healthy men. Surface EMG data were recorded bilaterally from the masseter and SCM muscles. The data for each muscle were converted to ratios of the pre-stimulus maximum voluntary contraction activity for each subject and averaged across subjects. Means of these percentages were determined at several defined pre- and post-stimulus intervals. The results indicate that masseter inhibition was clearly elicited by the electrical and both forms of mechanical stimulation. SCM co-inhibition could be evoked by electrical and chin tap stimulation but not by forehead tap. The responses to these stimuli varied among subjects, from trial to trial, and within subjects depending on the experimental condition. The fact that it was possible for this co-inhibition to be evoked is presented as further indication of the functional coupling of the trigeminal and cervical systems.     

When is facial pain trigeminal neuralgia?

The pain of trigeminal neuralgia can be excruciating and debilitating. Fortunately, effective medical and surgical therapies for the disorder exist. Successful treatment hinges on thorough history taking and accurate diagnosis. Diagnostic evaluation of patients with orofacial pain should include complete head and neck, dental, and neurologic examinations combined with radiologic imaging of the head and appropriate laboratory tests.     

Chronic back pain

Low-back pain is a very common disease in Switzerland as elsewhere, with a prevalence of 65%. The pain is usually due to degeneration of the motion segment, but subsides spontaneously in some 95% of cases irrespective of the treatment. Only 5% of patients still have pain after one year; but account for over 80% of the costs due to low-back pain. Some patients can be helped by surgical fusion; however; preoperative identification of the pain source is mandatory. Since there is no consistent correlation between pain and the degree of degeneration of motion segments as seen on plain radiographs, functional radiographs, CT scan or MRI, other diagnostic methods such as facet blocks, discography and external diagnostic fixation must be used. After careful patient selection a fusion operation may be considered. Good results after fusion operations are reported in 60-80% of patients. The operative techniques are described.     

Chronic pelvic pain

A total of 819 male and female skulls (frontal sections of 250 of these) were examined by traditional craniometry and MBS-2 microscope in order to assess the variability of morphogeometric parameters of biomechanical resistance of human brain skull and designing its structure typology. The following types of construction resistance of human brain skull (craniotypes) were distinguished: 1) structure resistant; 2) configuration resistant; 3) morphologically resistant; and 4) morphologically unstable.     

Chronic pain in elderly people

Using the fear-potentiated startle paradigm in rats, 4 experiments examined whether the inhibitory effect of a feature is evident after its offset following serial feature-negative discrimination training (A+ and X-->A-). When startle probes were presented shortly after the offset of X on X-->A test trials, the inhibitory properties of X were observed immediately after its offset. Furthermore, trace reinforcement of X (X-->+), but not delay reinforcement (X+), disrupted the ability of X to inhibit fear-potentiated startle on X-->A trials. Trace conditioning to X was also retarded after A+ and X-->A- training. These results suggest that the inhibitory properties of the serially trained feature are present after its offset and raise the possibility that either temporal information regarding nonreinforcement or poststimulus attributes of X acquire inhibitory properties.     

An animal model of neuropathic pain: a review

Recent work has succeeded in producing models of painful peripheral neuropathies in laboratory animals. There is evidence that the animals experience both abnormal spontaneous pain and abnormal evoked pains (allodynia and hyperalgesia). Experimental analyses of these models have demonstrated potential pathophysiologic mechanisms in both the peripheral and central nervous systems; it is likely that the model neuropathic pain syndromes are due to several different mechanisms. One line of evidence suggests that these pain states gradually become centralized due to an excitotoxic effect on spinal cord dorsal horn inhibitory interneurons. The role of the sympathetic nervous system appears to vary, depending on the type of nerve injury and the temporal evolution of the syndrome. There is evidence indicating that the abnormality of cutaneous temperature regulation that often accompanies painful peripheral neuropathy is not necessarily due to the activity of sympathetic vasomotor efferents.     

Correlation between autotomy-behavior and current theories of neuropathic pain

The past 10 years have brought several new experimental models with which to study chronic neuropathic pain in animals. Consequently, our knowledge about the mechanisms subserving neuropathic pain in humans has improved. However, the first animal model that was used for studying this type of chronic pain was the autotomy-model which can still be considered as a useful tool for pain studies. The present review assesses some of the similarities and differences between autotomy-model and more recent models of experimental traumatic mononeuropathy. In addition, it considers some of the similarities between the results obtained in clinical studies and in autotomy studies.     

Chronic low back pain

Most episodes of low back pain are mechanical in origin and resolve within a 12-week period. These acute episodes of back pain are associated with muscle strain and intervertebral disc herniation with radiculopathy. A smaller proportion of individuals have back pain with a duration greater than 12 weeks. These patients have back pain secondary to a wide variety of mechanical and nonmechanical disorders. The mechanical disorders associated with chronic low back pain include osteoarthritis and lumbar spinal stenosis; the nonmechanical disorders include infectious, neoplastic, rheumatologic, endocrinologic, vascular, and gynecologic. The clinical symptoms associated with each variety of disorder helps guide the appropriate diagnostic evaluation. Plain roentgenograms are useful in documenting the presence of spinal stenosis, benign or malignant tumors, osteoporosis, sacroiliitis, and spondylitis. CT scan is helpful in defining the bony alterations associated with malignant tumors and the vascular abnormalities associated with aneurysms. MR imaging is the technique of choice to document the extent of malignant processes and the presence of endometriosis in the pelvis. The therapy of these entities are specific for the disease entity causing the chronic low back pain. Although most of the disorders that cause chronic low back pain cannot be cured, therapy can decrease pain and improve function of the symptomatic patient.     

Chronic pain management in the workplace

1. Occupational health nurses often have the opportunity and knowledge to assist clients with chronic pain management and help them progress toward a more active and fulfilling lifestyle. 2. Proper pain management is considered one of the major concerns of modern health care. Health providers continue to search for ways to explain, predict, and cure the misery caused by chronic pain. 3. Chronic pain management is a multifacted condition of both mind and body and is heavily influenced by environmental factors such a family, cultural norms, and job expectations. 4. Current chronic pain management strategies focus on the whole person, not just the painful symptoms experienced by the individual.     

Arteriovenous differences in plasma concentrations of catechols in rats with neuropathic pain

BACKGROUND: Alterations in cutaneous temperature, sweating, and cutaneous blood flow in patients with pain states, such as reflex sympathetic dystrophy and causalgia, have been interpreted as evidence for exaggerated sympathetic outflow. It was determined whether pain behavior in a rat model of sympathetically maintained pain is associated with alterations in regional sympathoneural function. METHODS: Peripheral neuropathy was induced in 29 Sprague-Dawley rats by ligation of the left L5 and L6 spinal nerves. Sixteen other rats had sham surgery (nerve exposure without ligation). Animals were tested for behavioral signs of allodynia (decreased paw withdrawal thresholds to mechanical stimuli) at 2 and 4 weeks after the surgery. Arterial and iliac venous blood samples (left, affected; right, control) were obtained at 2 weeks (NP2, n = 14) and 4 weeks (NP4, n = 15) after neuropathic or sham (n = 8 at 2 and 4 weeks) surgery. Plasma concentrations of dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, norepinephrine, and the intraneuronal norepinephrine metabolite, 3,4-dihydroxyphenylglycol, were analyzed in arterial and left and right iliac venous samples. RESULTS: A decrease in paw withdrawal threshold was observed in neuropathic (NP2 and NP4) but not sham-operated rats. Affected and control limbs did not differ in arteriovenous differences in concentrations of dihydroxyphenylalanine, dihydroxyphenylacetic acid, dopamine, or 3,4-dihydroxyphenylglycol. No differences were observed between sham-operated and neuropathic animals in these arteriovenous increments. In contrast, affected limbs of NP2 rats had a reduced arteriovenous increment in norepinephrine concentrations, compared to that in the control side (P < 0.05). CONCLUSIONS: No neurochemical evidence of sympathetic hyperactivity is observed in the rat model of neuropathic pain; if anything, norepinephrine release is decreased in the affected limb. Autonomic disturbances in neuropathic pain are therefore more likely the result of receptor supersensitivity than increased local sympathoneural traffic.