The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment, and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors, is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness as well as on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.

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The Biopsychosocial Approach to Chronic Pain: Scientific Advances and Future Directions

Peripheral tissue damage or nerve injury often leads to pathological pain processes, such as spontaneous pain, hyperalgesia and allodynia, that persist for years or decades after all possible tissue healing has occurred. Although peripheral neural mechanisms, such as nociceptor sensitization and neuroma formation, contribute to these pathological pain processes, recent evidence indicates that changes in central neural function may also play a significant role. In this review, we examine the clinical and experimental evidence which points to a contribution of central neural plasticity to the development of pathological pain. We also assess the physiological, biochemical, cellular and molecular mechanisms that underlie plasticity induced in the central nervous system (CNS) in response to noxious peripheral stimulation. Finally, we examine theories which have been proposed to explain how injury or noxious stimulation lead to alterations in CNS function which influence subsequent pain experience.

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Contribution of central neuroplasticity to pathological pain: review of clinical and experimental evidence

1. The neuronal mechanisms underlying the major motor signs of Parkinson's disease were studied in the basal ganglia of parkinsonian monkeys. Three African green monkeys were systemically treated w...

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The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism

A MUCH debated question is whether sex differences exist in the functional organization of the brain for language1–4. A long-held hypothesis posits that language functions are more likely to be highly lateralized in males and to be represented in both cerebral hemispheres in females5,6, but attempts to demonstrate this have been inconclusive7–17. Here we use echo-planar functional magnetic resonance imaging18–21 to study 38 right-handed subjects (19 males and 19 females) during orthographic (letter recognition), phonological (rhyme) and semantic (semantic category) tasks. During phonological tasks, brain activation in males is lateralized to the left inferior frontal gyrus regions; in females the pattern of activation is very different, engaging more diffuse neural systems that involve both the left and right inferior frontal gyrus. Our data provide clear evidence for a sex difference in the functional organization of the brain for language and indicate that these variations exist at the level of phonological processing.

Sex differences in the functional organization of the brain for language

Tremor was suppressed by test stimulation of the thalamic ventralis intermedius (VIM) nucleus at high frequency (130 Hz) during stereotaxy in nonanesthetized patients suffering from Parkinson's disease or essential tremor. Ventralis intermedius stimulation has since been used by the authors over the last 8 years as a treatment in 117 patients with movement disorders (80 cases of Parkinson's disease, 20 cases of essential tremor, and 17 cases of various dyskinesias and dystonias including four multiple sclerosis). Chronic electrodes were stereotactically implanted in the VIM and connected to a programmable stimulator. Results depend on the indication. In Parkinson's disease patients, tremor, but not bradykinesia and rigidity, was selectively suppressed for as long as 8 years. Administration of L-Dopa was decreased by more than 30% in 40 Parkinson's disease patients. In essential tremor patients, results were satisfactory but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their but deteriorated with time in 18.5% of cases, mainly for patients who presented an action component of their tremor. In other types of dyskinesias (except multiple sclerosis), results were much less favorable. Fifty-nine patients underwent bilateral implantation and 14 other patients received implantation contralateral to a previous thalamotomy. Thirty-seven patients (31.6%) experienced minor side effects, which were always well tolerated and immediately reversible. Three secondary scalp infections led to temporary removal of the implanted material. There was no permanent morbidity. This tremor suppression effect could be due to the inhibition or jamming of a retroactive loop. Chronic VIM stimulation, which is reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery (74 of 117 patients) and by elderly patients, should replace thalamotomy in the regular surgical treatment of parkinsonian and essential tremors.

Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders

Neurosurgical treatment of Parkinson's disease (PD) frequently employs chronic high-frequency deep brain stimulation (DBS) within the internal segment of globus pallidus (GPi) and can very effectiv...

Microstimulation-induced inhibition of neuronal firing in human globus pallidus.

Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.

https://www.jneurosci.org/content/jneuro/8/3/754.full.pdf

Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor

✓ This study was conducted to determine the safety and efficacy of multilevel anterior cervical corpectomy and stabilization using fibular allograft in patients with cervical myelopathy. Thirty-six patients underwent this procedure for cervical myelopathy caused by spondylosis (20 patients), ossified posterior longitudinal ligament (four patients), trauma (one patient), or a combination of lesions (11 patients). The mean age (± standard deviation) of the patients was 58 ± 10 years and 30 of the patients were men. The mean duration of symptoms before surgery was 30 ± 6 months and 11 patients had undergone previous surgery. Prior to surgery, the mean Nurick grade of the myelopathy was 3.1 ± 1.4. Seventeen patients also had cervicobrachial pain. Four vertebrae were removed in six patients, three in 19, and two in 11 patients. Instrumentation was used in 15 cases. The operative mortality rate was 3% (one patient) and two patients died 2 months postoperatively. Postoperative complications included early graft ...

Multilevel anterior cervical corpectomy and fibular allograft fusion for cervical myelopathy

Many previous studies have demonstrated the existence of neurons with tremor-frequency activity (”tremor cells”) in the thalamus of Parkinson’s disease (PD) patients and these neurons are presumed to play a role in the pathogenesis of tremor. Since a major input to motor thalamus (Voa and Vop) is from the internal segment of the globus pallidus (GPi), neurons with tremor-frequency activity in motor thalamus may receive input from neurons in GPi. The aim of this study was to quantify the characteristics of tremor cells in human globus pallidus. In three PD patients with tremor undergoing microelectrode exploration of the globus pallidus prior to pallidotomy, 228 neurons were sampled, and 28 (12.3%) were identified to fire at the same frequency as the tremor. These ”tremor cells” were located in the ventral portion of GPi. Autocorrelogram analysis of the sampled spike trains of these 28 tremor cells was carried out over sequential 10-s time segments, and autocorrelograms showing maximal oscillatory activity were graded from 0 to 10. Average tremor cell oscillation grades ranged from 6.8 to 7.8, similar to those reported in the MPTP-induced primate model of parkinsonism. The average tremor cell oscillation grade varied between patients, as did the clinical measures of tremor severity. Tremor cells had oscillations in spike discharges at the same average frequency (4.2–5.2 Hz) as the patient’s tremor determined from the electromyogram and accelerometry records of one or more limbs (4.0–5.4 Hz), and the individual values were correlated (r

 2=0.73) over the total range (3.7–5.6 Hz). The results of this study demonstrate the presence of neurons with 4–6 Hz tremor-frequency activity in GPi, supporting a role of the globus pallidus in the production of rest tremor in PD patients.

Identification and characterization of neurons with tremor-frequency activity in human globus pallidus.

We have performed single unit analysis of the activity of cells located in the ventral nuclear group of thalamus in a patient with dysesthetic pain below the level of a clinically complete traumatic spinal cord transection at C5. Cells located in the parasagittal plane 14 mm lateral to the midline responded to tactile stimulation in small facial and intraoral receptive fields, which were characteristic of patients without somatosensory abnormality [30]. In this patient the 16 mm lateral parasagittal plane contained cells with receptive fields located on the occiput and neck instead of the upper extremity as would normally be expected. Cells with receptive fields on the neck and occiput had not previously been observed in recordings from single units (n = 531) responding to somatosensory stimulation [30]. Thus, on the basis of their location in a region of thalamus which normally represents parts of the body below the level of the spinal cord transection and their unusual receptive fields adjacent to these same parts of the body, we propose that the cells in the 16 mm lateral plane have lost their normal afferent input. Analysis of the autopower spectra of spike trains indicates that cells in the 16 mm lateral plane exhibited a higher mean firing rate and greater tendency to fire in bursts than cells in the 14 mm lateral plane (P

R.R. Tasker

Papers

Microstimulation-induced inhibition of neuronal firing in human globus pallidus.

Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor

Multilevel anterior cervical corpectomy and fibular allograft fusion for cervical myelopathy

Identification and characterization of neurons with tremor-frequency activity in human globus pallidus.

Abnormal single-unit activity recorded in the somatosensory thalamus of a quadriplegic patient with central pain.