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Nociceptive Pathways (nociceptive + pathway)

Distribution by Scientific Domains

Life Sciences	57%
Medical Sciences	42%

Selected Abstracts

Peripheral sensitization in migraine,role for P2X purinergic receptors in the dura,vascular sensory pathway

DRUG DEVELOPMENT RESEARCH, Issue 6 2007
Ernest A. Jennings
Abstract Peripheral sensitization is still considered a prime contributor underlying the mechanisms of migraine. Trigeminal primary afferent neurons are the first neurons in the dural nociceptive pathway, and activation results in conscious perception of pain. Peripheral sensitization can lower the activation threshold of primary afferent neurons, rendering them more excitable, allowing for increases in release of neurotransmitter from both central and peripheral terminals. Increase in neurotransmitter release from central terminals contributes to excitation of second-order neurons, while the release of peptides from peripheral terminals has been implicated in neurogenic inflammation. Adenosine 5,-triphosphate (ATP) causes pain in human studies, and depolarize sensory neurons. There is evidence of the action of ATP at many levels in the dura,vascular sensory pathway. Animal studies have shown that some P2X receptors are located in neurons innervating the dura, including the P2X3 receptor, which is most often shown to be involved in nociceptive pathways. In this article, we briefly review peripheral sensitization in relation to migraine and provide emphasis for P2X receptor involvement where it is available. Drug Dev Res 68:321,328, 2007. © 2007 Wiley-Liss, Inc. [source]

Temperature perception and nociception

DEVELOPMENTAL NEUROBIOLOGY, Issue 1 2004
Barry G. Green
Abstract The specificity theory of somesthesis holds that perceptions of warmth, cold, and pain are served by separate senses. Although no longer accepted in all its details, the theory's basic assumptions of anatomical and functional specificity have remained guiding principles in research on temperature perception and its relationship to pain. This article reviews the response characteristics of thermoreceptors, temperature-sensitive nociceptors, and their associated pathways in the context of old and new perceptual phenomena, most of which cannot be satisfactorily explained by the specificity theory. The evidence indicates that throughout most of the perceptual range, temperature sensitivity depends upon coactivation of, and interactions among, thermal and nociceptive pathways that are composed of both specific "labeled lines" and nonspecific, multimodal fibers. Adding to this complexity is evidence that tactile stimulation can influence the way in which thermal stimulation is perceived. It is argued that thermoreception is best defined as a functional subsystem of somesthesis that serves the very different and sometimes conflicting demands of thermoregulation, protection from thermal injury, and haptic perception. © 2004 Wiley Periodicals, Inc. J Neurobiol 61: 13,29, 2004 [source]

Peripheral sensitization in migraine,role for P2X purinergic receptors in the dura,vascular sensory pathway

Neuronal nitric oxide synthase (nNOS) mRNA is down-regulated, and constitutive NOS enzymatic activity decreased, in thoracic dorsal root ganglia and spinal cord of the rat by a substance P N-terminal metabolite

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2001
Katalin J. Kovacs
Abstract Nitric oxide (NO) in the spinal cord plays a role in sensory and autonomic activity. Pain induced by acetic acid in the abdominal stretch (writhing) assay and hyperalgesia associated with chronic pain are highly sensitive to NO synthase (NOS) inhibitors. Because substance P (SP) is released and up-regulated in some models of chronic pain, we hypothesized that an accumulation of SP metabolites may influence NOS expression and activity. To test this hypothesis, we examined the effect of intrathecally (i.t.) injected substance P (1-7) [SP(1-7)], the major metabolite of SP in the rat, on neuronal NOS (nNOS) mRNA in the thoracic and lumbar spinal cord, dorsal root ganglia (DRG) and on the corresponding constitutive NOS (cNOS) enzyme activity. Detected using quantitative RT-PCR, nNOS mRNA content in the thoracic spinal cord was decreased 6 h after injection of 5 µmol of SP(1-7) and returned to control 2 days later. In thoracic DRG, nNOS mRNA was reduced 48 h after SP(1-7). The cNOS enzymatic activity in thoracic spinal tissue was gradually decreased to a minimum at 72 h. Down-regulation of NOS by SP(1-7) in the thoracic area appears to be highly associated with capsaicin-sensitive primary afferent neurons. No similar changes in either parameter were measured in the lumbar area after SP(1-7). These data suggest that N-terminal SP fragments, which are known to cause long-term antinociception in the writhing assay, may do so by their ability to down-regulate NO synthesis along nociceptive pathways. [source]

Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5

GENES, BRAIN AND BEHAVIOR, Issue 2 2007
K.-S. Kim
Chronic inflammatory and neuropathic pain is often difficult to manage using conventional remedies. The underlying mechanisms and therapeutic strategies required for the management of chronic pain need to be urgently established. The cyclic AMP (cAMP) second messenger system has been implicated in the mechanism of nociception, and the inhibition of the cAMP pathway by blocking the activities of adenylyl cyclase (AC) and protein kinase A has been found to prevent chronic pain in animal models. However, little is known regarding which of the 10 known isoforms of AC are involved in nociceptive pathways. Therefore, we investigated the potential pronociceptive function of AC5 in nociception using recently developed AC5 knockout mice (AC5,/,). We found that AC5,/, mice show markedly attenuated pain-like responses in acute thermal and mechanical pain tests as compared with the wildtype control. Also, AC5,/, mice display hypoalgesic responses to inflammatory pain induced by subcutaneous formalin injection into hindpaws, and to non-inflammatory and inflammatory visceral pain induced by injecting magnesium sulfate or acetic acid into the abdomen. Moreover, AC5,/, mice show strongly suppressed mechanical and thermal allodynia in two nerve injury-induced neuropathic pain models. These results suggest that AC5 is essential for acute and chronic pain, and that AC5 knockout mice provide a useful model for the evaluation of the pathophysiological mechanisms of pain. [source]

Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity

HUMAN BRAIN MAPPING, Issue 9 2006
Jian Kong
Abstract Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input. Hum Brain Mapp, 2005. © 2005 Wiley-Liss, Inc. [source]

Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model

ARTHRITIS & RHEUMATISM, Issue 10 2010
Hee-Jeong Im
Objective To verify the biologic links between progressive cellular and structural alterations within knee joint components and development of symptomatic chronic pain that are characteristic of osteoarthritis (OA), and to investigate the molecular basis of alterations in nociceptive pathways caused by OA-induced pain. Methods An animal model of knee joint OA pain was generated by intraarticular injection of mono-iodoacetate (MIA) in Sprague-Dawley rats, and symptomatic pain behavior tests were performed. Relationships between development of OA with accompanying pain responses and gradual alterations in cellular and structural knee joint components (i.e., cartilage, synovium, meniscus, subchondral bone) were examined by histologic and immunohistologic analysis, microscopic examination, and microfocal computed tomography. Progressive changes in the dynamic interrelationships between peripheral knee joint tissue and central components of nociceptive pathways caused by OA-induced pain were examined by investigating cytokine production and expression in sensory neurons of the dorsal root ganglion and spinal cord. Results We observed that structural changes in components of the peripheral knee joint correlate with alterations in the central compartments (dorsal root ganglia and the spinal cord) and symptomatic pain assessed by behavioral hyperalgesia. Our comparative gene expression studies revealed that the pain pathways in MIA-induced knee OA may overlap, at least in part, with neuropathic pain mechanisms. Similar results were also observed upon destabilization of the knee joint in the anterior cruciate ligament transection and destabilization of the medial meniscus models of OA. Conclusion Our results indicate that MIA-induced joint degeneration in rats generates an animal model that is suitable for mechanistic and pharmacologic studies on nociceptive pain pathways caused by OA, and provide key in vivo evidence that OA pain is caused by central sensitization through communication between peripheral OA nociceptors and the central sensory system. Furthermore, our data suggest a mechanistic overlap between OA-induced pain and neuropathic pain. [source]