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Pain Pathways (pain + pathway)
Selected AbstractsA Pain Severity,Hypothalamic,Pituitary,Adrenocortical Axis Interaction: The Effects on Pain Pathways,JOURNAL OF APPLIED BIOBEHAVIORAL RESEARCH, Issue 1 2007John P. Garofalo Recent efforts have identified psychosocial and biological factors influencing the pathogenesis of chronic pain. The present study attempted to identify whether these two variables interact and, in turn, represent an underlying mechanism in the transition from acute to chronic pain. Salivary cortisol samples were collected upon waking up and 20 minutes later daily for 2 weeks from acute pain patients. Analyses revealed a direct relationship between pain severity and hypothalamic,pituitary,adrenocortical activity for temporomandibular disorder, and a negative relationship between these variables for low back pain populations. These results highlight the possible interaction between neuroendocrine and psychological factors to increase the risk for chronic pain. [source] DICHOTOMY OF CORTICAL PAIN PROCESSINGPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Jahangir Maleki, Rollin M. Gallagher, Pain Medicine and Rehabilitation Center, MCP/Hahnemann School of Medicine Introduction: Functional MRI and PET studies of cortical pain processing indicate segregated pain pathways above the thalamus. Although experimental pain may result in multiple areas of altered cortical activity, it is postulated that thalamic pain fibers known as the lateral system, projecting to sensory cortex, serve to localize pain, whereas medial pathways projecting to limbic cortex, process affective aspects of pain. Case Study: A 27 y/o female, with left upper extremity pain and severe allodynia from Complex Regional Pain Syndrome, Type I (CRPS I / RSD), after receiving intra-pleural bupivacaine blocks developed an ipsilateral focal-onset secondary generalized tonic clonic seizure. This was followed by one hour of post-ictal confusion. Simultaneously she developed a dense left-sided motor and sensory deficit (Todd's palsy) with a motor deficit resolving in one day whereas a sensory deficit lasted 2 days. Throughout the duration of the sensory deficit she denied any left arm pain, although she continued to report the same intensity of pain, but now localized to her epigastric region. Interestingly, despite the lack of sensory perception on the left side, palpation of her left arm resulted in increased epigastric pain and suffering. Discussion: This case indicates a bifurcation of the pain pathway between the thalamus and cortex. Due to focal seizure activity, the sensory cortex (i.e. lateral system) was transiently rendered dysfunctional, during which time the continued presence of pain and allodynia without appropriate localization likely resulted from pain conduction, from the thalamus to functional limbic structures such as Cingulum (i.e. via the medial fibre system). Conclusion: This case report strongly supports the hypothesis of medial and lateral pain conducting fibers branching at the level of thalamus with medial sub-serving the emotional aspects of pain by projection to limbic cortex, whereas lateral fibres project to sensory cortex, primarily serving a localizing function. [source] Protein kinase A-dependent enhanced NMDA receptor function in pain-related synaptic plasticity in rat amygdala neuronesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Gary C. Bird Mechanisms of pain-related plasticity in the amygdala, a key player in emotionality, were studied at the cellular and molecular levels in a model of arthritic pain. The influence of the arthritis pain state induced in vivo on synaptic transmission and N -methyl- d -aspartate (NMDA) receptor function was examined in vitro using whole-cell voltage-clamp recordings of neurones in the latero-capsular part of the central nucleus of the amygdala (CeA), which is now defined as the ,nociceptive amygdala'. Synaptic transmission was evoked by electrical stimulation of afferents from the pontine parabrachial area (part of the spino-parabrachio-amygdaloid pain pathway) in brain slices from control rats and from arthritic rats. This study shows that pain-related synaptic plasticity is accompanied by protein kinase A (PKA)-mediated enhanced NMDA-receptor function and increased phosphorylation of NMDA-receptor 1 (NR1) subunits. Synaptic plasticity in the arthritis pain model, but not normal synaptic transmission in control neurones, was inhibited by a selective NMDA receptor antagonist. Accordingly, an NMDA receptor-mediated synaptic component was recorded in neurones from arthritic animals, but not in control neurones, and was blocked by inhibition of PKA but not protein kinase C (PKC). Exogenous NMDA evoked a larger inward current in neurones from arthritic animals than in control neurones, indicating a postsynaptic effect. Paired-pulse facilitation, a measure of presynaptic mechanisms, was not affected by an NMDA-receptor antagonist. Increased levels of phosphorylated NR1 protein, but not of total NR1, were measured in the CeA of arthritic rats compared to controls. Our results suggest that pain-related synaptic plasticity in the amygdala involves a critical switch of postsynaptic NMDA receptor function through PKA-dependent NR1 phosphorylation. [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] Characterization of VR1 within the BMBF-Leitproject: ,Molecular Pain Research'JOURNAL OF NEUROCHEMISTRY, Issue 2003R. Jostock The vanilloid receptor VR1 is a ligand, heat and proton gated ion channel, expressed predominantly by primary sensory neurons. We show the molecular characterization of VR1 and its involvement in nociceptive behavior. Biochemical analysis of VR1 showed glycosylation at N604 and the predicted tetrameric structure. Reduced pH potentiated the gating of the receptor by NADA and anandamide in recombinant VR1. Acidification could sensitize VR1 and lead to hyperalgesia. Therefore, the VR1 antagonist capsazepine was tested in several animal models. Capsazepine reduced formalin induced nocifensive behavior and CFA induced mechanical hyperalgesia, and was antiallodynic and antihyperalgesic in animal models of neuropathic pain. VR1 antisense oligonucleotides inhibited VR1 expression in vitro and reduced tactile allodynia in vivo. In conclusion, we could provide evidence for a role of VR1 in inflammatory and neuropathic pain pathways. [source] Involvement of nerve injury and activation of peripheral glial cells in tetanic sciatic stimulation-induced persistent pain in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2010Lingli Liang Abstract Tetanic stimulation of the sciatic nerve (TSS) produces long-lasting pain hypersensitivity in rats. Long-term potentiation (LTP) of C- and A-fiber-evoked field potentials in the spinal cord has been explored as contributing to central sensitization in pain pathways. However, the peripheral mechanism underlying TSS-induced pain hypersensitivity remains largely unknown. We investigated the effect of TSS on peripheral nerve and the expression of activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) as a marker of neuronal injury. TSS induced a mechanical allodynia for at least 35 days and induced ATF3 expression in the ipsilateral DRG. ATF3 is colocalized with NF200-labeled myelinated DRG neurons or CGRP- and IB4-labeled unmyelinated ones. Furthermore, we found that TSS induced Wallerian degeneration of sciatic nerve at the level of myelinisation by S100 protein (to label Schwann cells) immunohistochemistry, luxol fast blue staining, and electron microscopy. TSS also elicited the activation of satellite glial cells (SGCs) and enhanced the colocalization of GFAP and P2X7 receptors. Repeated local treatment with tetrodotoxin decreased GFAP expression in SGCs and behavioral allodynia induced by TSS. Furthermore, reactive microglia and astrocytes were found in the spinal dorsal horn after TSS. These results suggest that TSS-induced nerve injury and glial activation in the DRG and spinal dorsal horn may be involved in cellular mechanisms underlying the development of persistent pain after TSS and that TSS-induced nerve injury may be used as a novel neuropathic pain model. © 2010 Wiley-Liss, Inc. [source] Pain management in horses and farm animalsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 4 2005Alexander Valverde DVM, DACVA Abstract Objective: This review discusses the different analgesic drugs and routes of administration used in large animals for acute pain management. General guidelines and doses are given to assist in choosing techniques that provide effective analgesia. Etiology: Noxious stimuli are perceived, recognized, and localized by specialized sensory systems located at spinal and supraspinal levels. Diagnosis: Localizing the source of the noxious stimulus as well as understanding the behavioral aspects and physiological changes that result from such insult is important to adequately diagnose and treat pain. Pain assessment is far from being definite and objective; not only are there species differences, but also individual variation. In addition, the behavioral and physiological manifestations vary with the acute or chronic nature of pain. Therapy: Pain management should include (1) selecting drugs that better control the type of pain elicited by the insult; (2) selecting techniques of analgesic drug administration that act on pathways or anatomical locations where the nociceptive information is being processed or originating from; (3) combining analgesic drugs that act on different pain pathways; and (4) provide the best possible comfort for the animal. Prognosis: Providing pain relief improves the animal's well being and outcome; however, interpreting and diagnosing pain remains difficult. Continuing research in pain management will contribute to the evaluation of the pathophysiology of pain, pain assessment, and newer analgesic drugs and techniques. [source] ,Protective premedication': an option with gabapentin and related drugs?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2004A review of gabapentin, pregabalin in the treatment of post-operative pain Substantial progress has been made during the last decades in our understanding of acute pain mechanisms, and this knowledge has encouraged the search for novel treatments. Of particular interest has been the observation that tissue injury initiates a number of modulations of both the peripheral and the central pain pathways, which convert the system from a ,physiological' to a ,pathological' mode of processing afferent information. Gabapentin, which binds to the ,2, subunit of the voltage-dependent calcium channel, is active in animal models of ,pathological' but not in models of ,physiological' pain. Consequently, attention has so far been focused on neuropathic pain as a target for the clinical use of gabapentin and analogues. Recently, several reports have indicated that gabapentin may have a place in the treatment of post-operative pain. This article presents a brief summary of the potential mechanisms of post-operative pain, and a systematic review of the available data of gabapentin and pregabalin for post-operative analgesia. It is concluded that the results with gabapentin and pregabalin in post-operative pain treatment published so far are promising. It is suggested that future studies should explore the effects of ,protective premedication' with combinations of various antihyperalgesic and analgesic drugs for post-operative analgesia. [source] Referred Pain Elicited by Manual Exploration of the Lateral Rectus Muscle in Chronic Tension-Type HeadachePAIN MEDICINE, Issue 1 2009César Fernández-de-las-Peñas PT ABSTRACT Objective., To analyze the presence of referred pain elicited by manual examination of the lateral rectus muscle in patients with chronic tension-type headache (CTTH). Design., A case-control blinded study. Setting., It has been found previously that the manual examination of the superior oblique muscle can elicit referred pain to the head in some patients with migraine or tension-type headache. However, a referred pain from other extraocular muscles has not been investigated. Methods., Fifteen patients with CTTH and 15 healthy subjects without headache history were included. A blinded assessor performed a manual examination focused on the search for myofascial trigger points (TrPs) in the right and left lateral rectus muscles. TrP diagnosis was made when there was referred pain evoked by maintained pressure on the lateral corner of the orbit (anatomical projection of the lateral rectus muscle) for 20 seconds, and increased referred pain while the subject maintained a medial gaze on the corresponding side (active stretching of the muscle) for 15 seconds. On each side, a 10-point numerical pain rate scale was used to assess the intensity of referred pain at both stages of the examination. Results., Ten patients with CTTH (66.6%) had referred pain that satisfied TrPs diagnostic criteria, while only one healthy control (0.07%) reported referred pain upon the examination of the lateral rectus muscles (P < 0.001). The elicited referred pain was perceived as a deep ache located at the supraorbital region or the homolateral forehead. Pain was evoked on both sides in all subjects with TrPs, with no difference in pain intensity between the right and the left. The average pain intensity was significantly greater in the patient group (P < 0.001). All CTTH patients with referred pain recognized it as the frontal pain that they usually experienced during their headache attacks, which was consistent with active TrPs. Conclusion., In some patients with CTTH, the manual examination of lateral rectus muscle TrPs elicits a referred pain that extends to the supraorbital region or the homolateral forehead. Nociceptive inputs from the extraocular muscles may sustain the activation of trigeminal neuron, thus sensitizing central pain pathways and exacerbating headache. [source] DICHOTOMY OF CORTICAL PAIN PROCESSINGPAIN MEDICINE, Issue 2 2002Article first published online: 4 JUL 200 Jahangir Maleki, Rollin M. Gallagher, Pain Medicine and Rehabilitation Center, MCP/Hahnemann School of Medicine Introduction: Functional MRI and PET studies of cortical pain processing indicate segregated pain pathways above the thalamus. Although experimental pain may result in multiple areas of altered cortical activity, it is postulated that thalamic pain fibers known as the lateral system, projecting to sensory cortex, serve to localize pain, whereas medial pathways projecting to limbic cortex, process affective aspects of pain. Case Study: A 27 y/o female, with left upper extremity pain and severe allodynia from Complex Regional Pain Syndrome, Type I (CRPS I / RSD), after receiving intra-pleural bupivacaine blocks developed an ipsilateral focal-onset secondary generalized tonic clonic seizure. This was followed by one hour of post-ictal confusion. Simultaneously she developed a dense left-sided motor and sensory deficit (Todd's palsy) with a motor deficit resolving in one day whereas a sensory deficit lasted 2 days. Throughout the duration of the sensory deficit she denied any left arm pain, although she continued to report the same intensity of pain, but now localized to her epigastric region. Interestingly, despite the lack of sensory perception on the left side, palpation of her left arm resulted in increased epigastric pain and suffering. Discussion: This case indicates a bifurcation of the pain pathway between the thalamus and cortex. Due to focal seizure activity, the sensory cortex (i.e. lateral system) was transiently rendered dysfunctional, during which time the continued presence of pain and allodynia without appropriate localization likely resulted from pain conduction, from the thalamus to functional limbic structures such as Cingulum (i.e. via the medial fibre system). Conclusion: This case report strongly supports the hypothesis of medial and lateral pain conducting fibers branching at the level of thalamus with medial sub-serving the emotional aspects of pain by projection to limbic cortex, whereas lateral fibres project to sensory cortex, primarily serving a localizing function. [source] Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain modelARTHRITIS & RHEUMATISM, Issue 10 2010Hee-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] Collagen-induced arthritis as a model of hyperalgesia: Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockadeARTHRITIS & RHEUMATISM, Issue 12 2007Julia J. Inglis Objective There is a disparity in the animal models used to study pain in rheumatoid arthritis (RA), which tends to be acute in nature, and models used to assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte-driven and polyarthritic. We assessed pain behavior and mechanisms in collagen-induced arthritis (CIA), the model of preclinical arthritis used most commonly in the field of immunology. We then validated the model using anti,tumor necrosis factor (anti-TNF) therapy, which has analgesic effects in models of inflammation as well as in human RA. Methods CIA was induced in DBA/1 mice by immunization with type II collagen at the base of the tail. Swelling and mechanical and thermal hyperalgesia were assessed before and for 28 days after the onset of arthritis. Spontaneous behavior was assessed using an automated activity monitor. Glial activity was assessed by glial fibrillary acidic protein expression, and nerve damage was evaluated by activating transcription factor 3 expression. The actions of anti-TNF therapy on nociception were then evaluated. Results Arthritis resulted in a decrease in the threshold for thermal and mechanical stimuli, beginning on the day of onset. Decreased spontaneous activity was also observed. A significant increase in the number of hyperplasic spinal cord astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF therapy was profoundly analgesic, with an efficacy similar to that of cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA. Conclusion This study shows that the CIA model is suitable for testing not only antiinflammatory but also analgesic drugs for potential use in RA, and highlights the importance of using appropriate disease models to assess relevant pain pathways. [source] | |||||||||||||