Biomedical subjects

A Vania Apkarian

Publications and source records attributed to A Vania Apkarian.

15 recordsLinked to original sources

PubMed2006

Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain.

Living with unrelenting pain (chronic pain) is maladaptive and is thought to be associated with physiological and psychological modifications, yet there is a lack of knowledge regarding brain elements involved in such conditions. Here, we identify brain regions involved in spontaneous pain of chronic back pain (CBP) in two separate groups of patients (n = 13 and n = 11), and contrast brain activity between spontaneous pain and thermal pain (CBP and healthy subjects, n = 11 each). Continuous ratings of fluctuations of spontaneous pain during functional magnetic resonance imaging were separated into two components: high sustained pain and increasing pain. Sustained high pain of CBP resulted in increased activity in the medial prefrontal cortex (mPFC; including rostral anterior cingulate). This mPFC activity was strongly related to intensity of CBP, and the region is known to be involved in negative emotions, response conflict, and detection of unfavorable outcomes, especially in relation to the self. In contrast, the increasing phase of CBP transiently activated brain regions commonly observed for acute pain, best exemplified by the insula, which tightly reflected duration of CBP. When spontaneous pain of CBP was contrasted to thermal stimulation, we observe a double-dissociation between mPFC and insula with the former correlating only to intensity of spontaneous pain and the latter correlating only to pain intensity for thermal stimulation. These findings suggest that subjective spontaneous pain of CBP involves specific spatiotemporal neuronal mechanisms, distinct from those observed for acute experimental pain, implicating a salient role for emotional brain concerning the self.

Atrophy↗

PubMed2006

Expression of IL-1beta in supraspinal brain regions in rats with neuropathic pain.

We examined mRNA expression of the pro-inflammatory cytokine IL-1beta in the brainstem, thalamus, and prefrontal cortex in two rat models of neuropathic pain. Rats received a neuropathic injury: spared nerve injury (SNI) or chronic constriction injury (CCI), sham injury, or were minimally handled (control). Neuropathic pain-like behavior was monitored by tracking tactile thresholds. SNI-injured animals showed a robust decrease in tactile thresholds of the injured foot, while CCI-injured animals did not show tactile threshold changes. Ten or 24 days after nerve injury, IL-1beta gene expression in the brain was determined by RT-PCR. IL-1beta expression changes were observed mainly at 10 days after injury in the SNI animals, contralateral to the injury side, with increased expression in the brainstem and prefrontal cortex. The results indicate that neuro-immune activation in neuropathic pain conditions includes supraspinal brain regions, suggesting cytokine modulation of supraspinal circuitry of pain in neuropathic conditions.

Animals↗

PubMed2006

Inflammatory and neuropathic pain animals exhibit distinct responses to innocuous thermal and motoric challenges.

Most current methods for assessing pain in animals are based on reflexive measures and require constant interaction between the observer and the animal. Here we explore two new fully automated methods to quantify the impact of pain on the overall behavior of the organism. Both methods take advantage of the animals' natural preference for a dark environment. We used a box divided into two compartments: dark and bright. In the motoric operant task, "AngleTrack", one end of the box was raised so that the animals had to climb uphill to go from the light to the dark compartment. In the thermal operant task, "ThermalTrack", the floor of the dark compartment was heated to a given temperature, while the light compartment remained at 25 degrees C. Rats were individually placed in the light box and their crossing between chambers monitored automatically for 30 minutes. The angle of the box, or the temperature of the dark compartment, was altered to challenge the animals' natural preference. We test the hypothesis that different models of pain (inflammatory or neuropathic) can be differentiated based on performance on these devices. Three groups of rats were tested at five different challenge levels on both tasks: 1) normal, 2) neuropathic injury pain (Spared Nerve Injury), and 3) inflammatory pain (intraplantar injection of Carrageenan). We monitored the position of the animals as well as their rate of switching between compartments. We find significant differences between the three groups and between the challenge levels both in their average position with respect to time, and in their switching rates. This suggests that the angle-track and thermal-track may be useful in assessing automatically the global impact of different types of pain on behavior.

Animals↗

PubMed2005

Dynamics of pain: fractal dimension of temporal variability of spontaneous pain differentiates between pain States.

Spontaneous pain is a common complaint in chronic pain conditions. However, its properties have not been explored. Here we study temporal properties of spontaneous pain. We examine time variability of fluctuations of spontaneous pain in patients suffering from chronic back pain and chronic postherpetic neuropathy and contrast properties of these ratings to normal subjects' ratings of either acute thermal painful stimuli or of imagined back pain. Subjects are instructed to continuously rate their subjective assessment of the intensity of pain over a 6- to 12-min period. We observe that the fluctuations of spontaneous pain do not possess stable mean or variance, implying that these time series can be better characterized by fractal analysis. To this end, we apply time and frequency domain techniques to characterize variability of pain ratings with a single parameter: fractal dimension, D. We demonstrate that the majority of ratings of spontaneous pain by the patients have fractal properties, namely they show a power law relationship between variability and time-scale length; D is distinct between types of chronic pain, and from ratings of thermal stimulation or of imagined pain; and there is a correspondence between D for pain ratings and D for brain activity, in chronic back pain patients using fMRI. These results show that measures of variability of spontaneous pain differentiate between chronic pain conditions, and thus may have mechanistic and clinical utility.

Adult↗

PubMed2005

Spared nerve injury rats exhibit thermal hyperalgesia on an automated operant dynamic thermal escape task.

Well-established methods are available to measure thermal and mechanical sensitivity in awake behaving rats. However, they require experimenter manipulations and tend to emphasize reflexive behaviors. Here we introduce a new behavioral test, with which we examine thermal sensitivity of rats with neuropathic injury. We contrast thermal hyperalgesia between spared nerve injury and chronic constriction injury rats. This device is a fully automated thermal sensitivity assessment tool designed to emphasize integrated learned responses to thermal painful and non-painful stimuli that are applied dynamically to a surface on which the animal is standing. It documents escape behavior in awake, unrestrained animals to innocuous and noxious heating of the floor where the animal is located. Animals learn to minimize pain by escaping to the opposite non-heated side; escape latency is recorded. On this device, thermal stimulus-response curves showed > 6 degrees C leftward shift in both groups of neuropathic rats. In contrast, when these animals were tested on hotplate the stimulus-response shift was < 2 degrees C. Spared nerve injury rats showed even less evidence for thermal hyperalgesia when thermal sensitivity was tested by measuring paw withdrawal to infrared heating, plantar test. The implications of test dependent magnitude of thermal hyperalgesia are discussed from the viewpoint of the tests used, as well as the animal models studied. It is argued that the dynamic thermal operant task reveals the relevance of the neuropathic injury associated pain-like behavior in relation to the whole organism.

Animals↗

PubMed2005

Human brain mechanisms of pain perception and regulation in health and disease.

CONTEXT: The perception of pain due to an acute injury or in clinical pain states undergoes substantial processing at supraspinal levels. Supraspinal, brain mechanisms are increasingly recognized as playing a major role in the representation and modulation of pain experience. These neural mechanisms may then contribute to interindividual variations and disabilities associated with chronic pain conditions. OBJECTIVE: To systematically review the literature regarding how activity in diverse brain regions creates and modulates the experience of acute and chronic pain states, emphasizing the contribution of various imaging techniques to emerging concepts. DATA SOURCES: MEDLINE and PRE-MEDLINE searches were performed to identify all English-language articles that examine human brain activity during pain, using hemodynamic (PET, fMRI), neuroelectrical (EEG, MEG) and neurochemical methods (MRS, receptor binding and neurotransmitter modulation), from January 1, 1988 to March 1, 2003. Additional studies were identified through bibliographies. STUDY SELECTION: Studies were selected based on consensus across all four authors. The criteria included well-designed experimental procedures, as well as landmark studies that have significantly advanced the field. DATA SYNTHESIS: Sixty-eight hemodynamic studies of experimental pain in normal subjects, 30 in clinical pain conditions, and 30 using neuroelectrical methods met selection criteria and were used in a meta-analysis. Another 24 articles were identified where brain neurochemistry of pain was examined. Technical issues that may explain differences between studies across laboratories are expounded. The evidence for and the respective incidences of brain areas constituting the brain network for acute pain are presented. The main components of this network are: primary and secondary somatosensory, insular, anterior cingulate, and prefrontal cortices (S1, S2, IC, ACC, PFC) and thalamus (Th). Evidence for somatotopic organization, based on 10 studies, and psychological modulation, based on 20 studies, is discussed, as well as the temporal sequence of the afferent volley to the cortex, based on neuroelectrical studies. A meta-analysis highlights important methodological differences in identifying the brain network underlying acute pain perception. It also shows that the brain network for acute pain perception in normal subjects is at least partially distinct from that seen in chronic clinical pain conditions and that chronic pain engages brain regions critical for cognitive/emotional assessments, implying that this component of pain may be a distinctive feature between chronic and acute pain. The neurochemical studies highlight the role of opiate and catecholamine transmitters and receptors in pain states, and in the modulation of pain with environmental and genetic influences. CONCLUSIONS: The nociceptive system is now recognized as a sensory system in its own right, from primary afferents to multiple brain areas. Pain experience is strongly modulated by interactions of ascending and descending pathways. Understanding these modulatory mechanisms in health and in disease is critical for developing fully effective therapies for the treatment of clinical pain conditions.

Afferent Pathways↗

PubMed2005

Scale-free brain functional networks.

Functional magnetic resonance imaging is used to extract functional networks connecting correlated human brain sites. Analysis of the resulting networks in different tasks shows that (a) the distribution of functional connections, and the probability of finding a link versus distance are both scale-free, (b) the characteristic path length is small and comparable with those of equivalent random networks, and (c) the clustering coefficient is orders of magnitude larger than those of equivalent random networks. All these properties, typical of scale-free small-world networks, reflect important functional information about brain states.

Brain Mapping↗

PubMed2005

Brain imaging findings in neuropathic pain.

The contribution of brain imaging technologies to the understanding of mechanisms underlying clinical neuropathic conditions is discussed in this article. Available technologies, their advantages, and contributions also are presented. The brain regions involved in acute pain are contrasted to chronic pain and the implications of these differences are discussed. Overall, the reasons for the limited contribution of these techniques to the science of chronic pain are presented in this article.

Brain↗

PubMed2004

Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.

The role of the brain in chronic pain conditions remains speculative. We compared brain morphology of 26 chronic back pain (CBP) patients to matched control subjects, using magnetic resonance imaging brain scan data and automated analysis techniques. CBP patients were divided into neuropathic, exhibiting pain because of sciatic nerve damage, and non-neuropathic groups. Pain-related characteristics were correlated to morphometric measures. Neocortical gray matter volume was compared after skull normalization. Patients with CBP showed 5-11% less neocortical gray matter volume than control subjects. The magnitude of this decrease is equivalent to the gray matter volume lost in 10-20 years of normal aging. The decreased volume was related to pain duration, indicating a 1.3 cm3 loss of gray matter for every year of chronic pain. Regional gray matter density in 17 CBP patients was compared with matched controls using voxel-based morphometry and nonparametric statistics. Gray matter density was reduced in bilateral dorsolateral prefrontal cortex and right thalamus and was strongly related to pain characteristics in a pattern distinct for neuropathic and non-neuropathic CBP. Our results imply that CBP is accompanied by brain atrophy and suggest that the pathophysiology of chronic pain includes thalamocortical processes.

Aging↗

PubMed2004

Chronic pain patients are impaired on an emotional decision-making task.

Chronic pain can result in anxiety, depression and reduced quality of life. However, its effects on cognitive abilities have remained unclear although many studies attempted to psychologically profile chronic pain. We hypothesized that performance on an emotional decision-making task may be impaired in chronic pain since human brain imaging studies show that brain regions critical for this ability are also involved in chronic pain. Chronic back pain (CBP) patients, chronic complex regional pain syndrome (CRPS) patients, and normal volunteers (matched for age, sex, and education) were studied on the Iowa Gambling Task, a card game developed to study emotional decision-making. Outcomes on the gambling task were contrasted to performance on other cognitive tasks. The net number of choices made from advantageous decks after subtracting choices made from disadvantageous decks on average was 22.6 in normal subjects (n = 26), 13.4 in CBP patients (n = 26), and -9.5 in CRPS patients (n = 12), indicating poor performance in the patient groups as compared to the normal controls (P < 0.004). Only pain intensity assessed during the gambling task was correlated with task outcome and only in CBP patients (r = -0.75, P < 0.003). Other cognitive abilities, such as attention, short-term memory, and general intelligence tested normal in the chronic pain patients. Our evidence indicates that chronic pain is associated with a specific cognitive deficit, which may impact everyday behavior especially in risky, emotionally laden, situations.

Adult↗

PubMed2004

Cortical pathophysiology of chronic pain.

Studies in my laboratory have been employing multiple non-invasive brain imaging techniques to study the characteristics of patients with chronic pain. Some of these results are briefly outlined in this communication. Our studies regarding brain activity in chronic pain are summarized, emphasizing the unique role of the prefrontal cortex in chronic, especially neuropathic pain states. I also review our work examining brain chemistry abnormalities in chronic pain. Given these results, we have examined chronic pain patients in a cognitive task, designed to probe brain regions that we think are specifically abnormal in chronic pain, these results are also summarized. An overview of the mechanisms that may be pertinent to the observed results is included.

Brain Chemistry↗

PubMed2002

Mastalgia and breast cancer: a protective association?

Breast pain (mastalgia) is a common complaint, with a potentially important relationship to breast cancer risk. We have examined the association between mastalgia and breast cancer in the patient population of the Breast Care Center of University Hospital, Syracuse, New York. Of 5463 women with complete breast cancer risk factor information, 1532 (28%) reported breast pain as an incidental complaint at their initial visit, and 861 were diagnosed with breast cancer. Forward stepwise logistic regression was used to analyze the association between breast pain and a diagnosis of breast cancer. The age-adjusted OR for breast cancer was 0.60 (95% CI 0.50-0.74). Adjustment for additional risk factors (early menarche, late first birth, late menopause, exogenous hormone use, positive family history) yielded an OR of 0.63, 95% CI 0.49-0.79. Thus, women who experienced breast pain in our patient population were less likely to be diagnosed with breast cancer than women who did not complain of breast pain, regardless of age, and of other breast cancer risk factors. Further investigation of this possible protective association is warranted.

Adult↗

PubMed2002

The characteristics of cyclical and non-cyclical mastalgia: a prospective study using a modified McGill Pain Questionnaire.

Breast pain (mastalgia) is a common condition (usually classified as cyclical or non-cyclical) the characteristics of which have never been studied using a standardized pain instrument. We have modified the short form of the McGill Pain Questionnaire (SF-MPQ) for the measurement of mastalgia, and have administered it to 271 women with breast pain and without breast cancer. The mean pain-rating index (sum of 15 descriptors of SF-MPQ) was similar between cyclical and non-cyclical pain, and was 12.0 (of 45) for the entire group. When compared to similar studies of pain at other sites, this falls in the same range as chronic cancer pain, and just below the pain of rheumatoid arthritis. Mean %VAS (visual analog scale) was 45.12 and mean %PPI (present pain index) was 39.9. Most women described their pain as 'heavy, aching and tender,' and these descriptors were given significantly higher ratings by women with cyclical pain. In women with non-cyclical mastalgia, the overall pain severity was related to the size of the painful area, and the steadiness of the pain, and the affective components were more prominent than in women with cyclical mastalgia. Thus, cyclical and non-cyclical mastalgia show some differences in their characteristics with substantial overlap. The total breast pain score was most efficiently estimated by a combination of the VAS, the PPI, and the quality of life questions (R2 = 0.96). Studies of breast pain should include both groups to better understand and characterize these differences, particularly with regard to a possible connection with breast cancer risk.

Adolescent↗

PubMed2002

Peripheral inflammation increases the functional coherency of spinal responses to tactile but not nociceptive stimulation.

Reorganization of central networks and plasticity of neuronal representations have been implicated in recent years in the dynamic expression of somatosensory responses. The functional properties of spinal cells were shown to change in the scale of minutes after peripheral high-intensity stimulations and to undergo profound alterations in their responses in experimental models of chronic pain. These observations, however, are restricted to recordings from individual cells, and no information exists on how these changes may be reflected on the activity of somatosensory neuronal networks involved in pain processing. To understand how spinal cord networks may be altered after the onset of hyperalgesia, we extracellularly recorded from groups of five to nine neighboring neurons in the hindlimb representation area of the dorsal horn. The multineuronal activity evoked by cutaneous innocuous and noxious stimulation was compared before and for 3 h after the subcutaneous injection of diluted formalin. Formalin caused immediate changes in response properties and mechanical threshold of activation for the majority of the neurons and induced the incorporation of previously unresponsive neighboring neurons to the functional network. Analysis of the temporal correlation within the neuronal population revealed that formalin-induced inflammation increased the functional coherence of the network to the nonnociceptive stimulation but not to the painful stimuli. This increase in the tactile acuity of populations of nociceptive neurons may be a basis for the emergence of touch-evoked pain.

Animals↗

PubMed1989

A dorsolateral spinothalamic tract in macaque monkey.

Prior work has indicated the existence of a major spinal cord pathway made up of lamina I cell axons ascending in the dorsolateral funiculus in both rat and cat. In cat, a portion of this lamina I dorsolateral funiculus pathway terminates in the thalamus. The purpose of this report is to demonstrate that a similar dorsolateral spinothalamic tract exists in macaque monkey. Retrograde transport of horseradish peroxidase, injected into the somatosensory thalamus of monkeys, was used to identify the cells of origin of the spinothalamic tract in the cervical and lumbar enlargements. In order to determine the funicular courses of the axons contributing to the spinothalamic pathway, thalamic injections of horseradish peroxidase were combined with ipsilateral ventral or dorsolateral thoracic spinal cord lesions. The results indicate that in macaque monkey many lamina I cell axons ascend to the thalamus in the dorsolateral funiculus, contralateral to their parent cells. Some lamina I cell axons as well as the majority of axons of spinothalamic cells located in deeper laminae ascend in the contralateral ventral quadrant to terminate in the thalamus. The existence in macaque of a dorsolateral spinothalamic pathway comprised of lamina I cell axons strongly implies the presence of a similar pathway in humans and has important implications regarding the mechanisms underlying both clinical and experimental nociception.

Animals↗