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Nociceptive Transmission (nociceptive + transmission)
Selected AbstractsPre- and postsynaptic contributions of voltage-dependent Ca2+ channels to nociceptive transmission in rat spinal lamina I neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2004B. Heinke Abstract Activation of voltage-dependent Ca2+ channels (VDCCs) is critical for neurotransmitter release, neuronal excitability and postsynaptic Ca2+ signalling. Antagonists of VDCCs can be antinociceptive in different animal pain models. Neurons in lamina I of the spinal dorsal horn play a pivotal role in the processing of pain-related information, but the role of VDCCs to the activity-dependent Ca2+ increase in lamina I neurons and to the synaptic transmission between nociceptive afferents and second order neurons in lamina I is not known. This has now been investigated in a lumbar spinal cord slice preparation from young Sprague,Dawley rats. Microfluorometric Ca2+ measurements with fura-2 have been used to analyse the Ca2+ increase in lamina I neurons after depolarization of the cells, resulting in a distinct and transient increase of the cytosolic Ca2+ concentration. This Ca2+ peak was reduced by the T-type channel blocker, Ni2+, by the L-type channel blockers, nifedipine and verapamil, and by the N-type channel blocker, ,-conotoxin GVIA. The P/Q-type channel antagonist, ,-agatoxin TK, had no effect on postsynaptic [Ca2+]i. The NMDA receptor channel blocker D-AP5 reduced the Ca2+ peak, whereas the AMPA receptor channel blocker CNQX had no effect. Postsynaptic currents, monosynaptically evoked by electrical stimulation of the attached dorsal roots with C-fibre and A,-fibre intensity, respectively, were reduced by N-type channel blocker ,-conotoxin GVIA and to a much lesser extent, by P/Q-type channel antagonist ,-agatoxin TK, and the L-type channel blockers verapamil, respectively. No difference was found between unidentified neurons and neurons projecting to the periaqueductal grey matter. This is the first quantitative description of the relative contribution of voltage-dependent Ca2+ channels to the synaptic transmission in lamina I of the spinal dorsal horn, which is essential in the processing of pain-related information in the central nervous system. [source] Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTP,S binding in the dorsal horn of the spinal cord of noninflamed and inflamed ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000L. J. Drew Abstract The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5,-[,-[35S]thio]triphosphate ([35S]GTP,S) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300,800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTP,S binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTP,S binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states. [source] Abnormal substance P release from the spinal cord following injury to primary sensory neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2000Marzia Malcangio Abstract The neuropeptide substance P (SP) modulates nociceptive transmission within the spinal cord. Normally, SP is uniquely contained in a subpopulation of small-calibre axons (A,- and C-fibres) within primary afferent nerve. However, it has been shown that after nerve transection, besides being downregulated in small axons, SP is expressed de novo in large myelinated A,-fibres. In this study we investigated whether, following peripheral nerve injury, SP was released de novo from the spinal cord after selective activation of A,-fibres. Spinal cords with dorsal roots attached were isolated in vitro from rats 2 weeks following distal sciatic axotomy or proximal spinal nerve lesion (SNL). The ipsilateral dorsal roots were electrically stimulated for two consecutive periods at low- or high-threshold fibre strength, spinal cord superfusates were collected and SP content was determined by radioimmunoassay. SNL, but not axotomized or control rat cords, released significant amounts of SP after selective activation of A,-fibres. Not only do these data support the idea that A, myelinated fibres contribute to neuropathic pain by releasing SP, they also illustrate the importance of the proximity of the lesion to the cell body. [source] From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory systemJOURNAL OF ANATOMY, Issue 2 2007I. Tavares Abstract The endogenous pain modulatory system is a complex network of brain areas that control nociceptive transmission at the spinal cord by inhibitory and facilitatory actions. The balance between these actions ensures effective modulation of acute pain, while during chronic pain the pronociceptive effects appear to prevail. The mechanisms underlying this imbalance were studied as to the role of two medullary components of the pain modulatory system: the dorsal reticular nucleus and the caudal ventrolateral medulla, which function primarily as pronociceptive and antinociceptive centres, respectively. Both areas are connected with the spinal dorsal horn by closed reciprocal loops. In the spino-dorsal reticular nucleus loop, the ascending branch is strongly inhibited by spinal GABAergic neurons, which may act as a buffering system of the dorsal reticular nucleus-centred amplifying effect. In the spino-caudal ventrolateral medulla loop, the ascending branch is under potent excitation of substance P (SP) released from primary afferents, which is likely to trigger the intense descending inhibition detected in acute pain. During chronic pain, the activity in the lateral reticular formation of the caudal ventrolateral medulla changes, so that the action of the caudal ventrolateral medulla upon SP-responsive spinal neurons shifts from inhibitory to excitatory. The mechanisms of this modulatory shift are unknown but probably relate to the decresed expression of µ-opioid, ,-opioid and GABAB receptors. Normalizing receptor expression in the caudal ventrolateral medulla or controlling noci-evoked activity at the dorsal reticular nucleus or caudal ventrolateral medulla by interfering with neurotransmitter release is now possible by the use of gene therapy, an approach that stands out as a unique tool to manipulate the supraspinal endogenous pain control system. [source] Nitric oxide and pain: ,Something old, something new'ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009A. MICLESCU Challenges have emerged following the revival of nitric oxide (NO) from ,something old', a simple gas derived from nitrogen and oxygen with a role in the early stages of evolution, into ,something new', an endogenously formed biological mediator regulating a wide variety of physiological functions. Although pain is a common sensation, it encompasses multiple neurobiologic components, of which NO is only one. In pain research, the study of NO is complicated by convoluted problems related mostly to the effects of NO, which are pro- or anti-nociceptive depending on the circumstances. This dual function reflects the multi-faceted roles of the NO molecule described in physiology. This review covers current information about NO and its implications in pain mechanisms. In addition, it follows the pain pathways, demonstrating the role of NO in peripheral nociceptive transmission as well in central sensitization. This knowledge may provide the scientific basis for developing new drugs that are indicated for different types of pain, drugs that may be related to the chemical links of NO. A comprehensive approach to understanding the effects of NO will help clinicians identify novel agents that combine the pharmacological profile of native drugs with a controllable manner of NO release. Inhibitors of NO synthesis may have analgesic effects and would be of interest for treating inflammatory and neuropathic pain. Unfortunately, only a few of these compounds have reached the stage of clinical pain trials. [source] Rapid co-release of interleukin 1, and caspase 1 in spinal cord inflammationJOURNAL OF NEUROCHEMISTRY, Issue 3 2006Anna K. Clark Abstract Mounting evidence supports the hypothesis that pro-inflammatory cytokines secreted by astrocytes and microglia modulate nociceptive function in the injured CNS and following peripheral nerve damage. Here we examine the involvement of interleukin-1, (IL-1,) and microglia activation in nociceptive processing in rat models of spinal cord inflammation. Following application of lipopolysaccharide (LPS) to an ex vivo dorsal horn slice preparation, we observed rapid secretion of IL-1, which was prevented by inhibition of glial cell metabolism and by inhibitors of either p38 mitogen-activated protein kinase (MAPK) or caspase 1. LPS superfusion also induced rapid secretion of active caspase 1 and apoptosis-associated speck-like protein containing a caspase recruitment domain from the isolated dorsal horn. Extensive microglial cell activation in the dorsal horn, as determined by immunoreactivity for phosphorylated p38 MAPK, was found to correlate with the occurrence of IL-1, secretion. In behavioural studies, intrathecal injection of LPS in the lumbar spinal cord produced mechanical hyperalgesia in the rat hind-paws which was attenuated by concomitant injections of a p38 MAPK inhibitor, a caspase 1 inhibitor or the rat recombinant interleukin 1 receptor antagonist. These data suggest a critical role for the cytokine IL-1, and caspase 1 rapidly released by activated microglia in enhancing nociceptive transmission in spinal cord inflammation. [source] Investigations into the antinociceptive activity of Sapindus trifoliatus in various pain modelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2004D. K. Arulmozhi The effect of the aqueous extract of Sapindus trifoliatus (ST) on chemical, thermal-induced pain, nitroglycerin-induced hyperalgesia and pain on inflamed tissue was investigated. The extract (20 and 100 mg kg,1, i.p.) significantly inhibited acetic-acid-induced abdominal constrictions, formalin-induced pain licking and hotplate-induced pain in mice. Furthermore, the extract significantly increased the response latencies of nitroglycerin-induced hyperalgesia by the tail-flick method and mechanical pain on carrageenan-induced inflamed paw in rats. The data suggest that ST has an inhibitory activity on both peripheral and central pain mechanisms and has a modulatory role in NO-mediated nociceptive transmission. [source] Ventromedial medulla: Pain modulation and beyondTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2005Peggy Mason Abstract The midbrain periaqueductal gray (PAG) and ventromedial medulla (VMM) are generally viewed as the core of an endogenous descending modulatory system. However, available data demonstrate that PAG and VMM do not specifically target nociceptive transmission and that activation of either structure affects numerous homeostatic physiological processes. Pseudorabies virus (PRV) is a useful tracer that is retrogradely and transynaptically transported. PRV injections into homeostatic effector organs invariably label VMM neurons, both serotonergic and nonserotonergic. Studies in anesthetized rats have implicated two types of nonserotonergic VMM neurons in nociceptive modulation: ON cells are thought to facilitate nociception and OFF cells to inhibit nociception. Yet, in the unanesthetized animal, the discharge of VMM neurons changes in response to innocuous stimuli and during situations unrelated to nociception. In particular, VMM cells appear to modulate the timing of micturition, with ON cells promoting the initiation of voiding and OFF cells promoting urine storage. VMM cells also modulate sensory transmission. During both micturition and sleep, OFF cells discharge and sensory responsiveness is depressed. In sum, the VMM is hypothesized to modulate spinal sensory, autonomic, and motor circuits in order to maintain homeostasis. J. Comp. Neurol. 493:2,8, 2005. © 2005 Wiley-Liss, Inc. [source] Glutamate-mediated astrocyte-to-neuron signalling in the rat dorsal hornTHE JOURNAL OF PHYSIOLOGY, Issue 5 2010Rita Bardoni By releasing neuroactive agents, including proinflammatory cytokines, prostaglandins and neurotrophins, microglia and astrocytes are proposed to be involved in nociceptive transmission, especially in conditions of persistent, pathological pain. The specific action on dorsal horn neurons of agents released from astrocytes, such as glutamate, has been, however, poorly investigated. By using patch-clamp and confocal microscope calcium imaging techniques in rat spinal cord slices, we monitored the activity of dorsal horn lamina II neurons following astrocyte activation. Results obtained revealed that stimuli that triggered Ca2+ elevations in astrocytes, such as the purinergic receptor agonist BzATP and low extracellular Ca2+, induce in lamina II neurons slow inward currents (SICs). Similarly to SICs triggered by astrocytic glutamate in neurons from other central nervous system regions, these currents (i) are insensitive to tetrodotoxin (TTX), (ii) are blocked by the NMDA receptor (NMDAR) antagonist d -AP5, (iii) lack an AMPA component, and (iv) have slow rise and decay times. Ca2+ imaging also revealed that astrocytic glutamate evokes NMDAR-mediated episodes of synchronous activity in groups of substantia gelatinosa neurons. Importantly, in a model of peripheral inflammation, the development of thermal hyperalgesia and mechanical allodynia was accompanied by a significant increase of spontaneous SICs in dorsal horn neurons. The NMDAR-mediated astrocyte-to-neuron signalling thus represents a novel pathway that may contribute to the control of central sensitization in pathological pain. [source] | |||||||||||||||||||||||||