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Thermal Hyperalgesia (thermal + hyperalgesia)
Selected AbstractsDissociable neural activity to self- vs. externally administered thermal hyperalgesia: a parametric fMRI studyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2008C. Mohr Abstract Little is known regarding how cognitive strategies help to modulate neural responses of the human brain in ongoing pain syndromes to alleviate pain. Under pathological pain conditions, any self-elicited contact with usually non-painful stimuli may become painful. We examined whether the human brain is capable of dissociating self-controlled from externally administered thermal hyperalgesia in the experimental capsaicin model. Using functional magnetic resonance imaging, 17 male subjects were investigated in a parametric design with heat stimuli at topically capsaicin-sensitized skin. In contrast to external stimulation, self-administered pain was controllable. For both conditions application trials without noticeable thermal stimulation were introduced and used as high-level baseline (HLB) to account for the capsaicin-induced ongoing pain and other covariables. Following subtraction of the HLB, the anterior insula and the anterior cingulate cortex (ACC) but not the somatosensory cortices maintained parametric neural responses to thermal hyperalgesia. A stronger pain-related activity increase during self-administered stimuli was observed in the posterior insula. In contrast, prefrontal cortex showed stronger increases to uncontrollable external heat stimuli. In the state of ongoing pain (capsaicin), pain-intensity-encoding regions (anterior insula, ACC) but not those with sensory discriminative functions (SI, SII) showed graded, pain-intensity-related neural responses in thermal hyperalgesia. Some areas were able to dissociate between self- and externally administered stimuli in thermal hyperalgesia, which might be related to differences in perceived controllability. Thus, neural mechanisms maintain the ability to dissociate external from self-generated states of injury in thermal hyperalgesia. This may help to understand how cognitive strategies potentially alleviate chronic pain syndromes. [source] Neuropathic pain is enhanced in ,-opioid receptor knockout miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006Xavier Nadal Abstract We have evaluated the possible involvement of ,-opioid receptor (DOR) in the development and expression of neuropathic pain. For this purpose, partial ligation of the sciatic nerve was performed in DOR knockout mice and wild-type littermates. The development of mechanical and thermal allodynia, as well as thermal hyperalgesia was evaluated by using the von Frey filament model, the cold-plate test and the plantar test, respectively. In wild-type and DOR knockout mice, sciatic nerve injury led to a neuropathic pain syndrome revealed in these nociceptive behavioural tests. However, the development of mechanical and thermal allodynia, and thermal hyperalgesia was significantly enhanced in DOR knockout mice. These results reveal the involvement of DOR in the control of neuropathic pain and suggest a new potential therapeutic use of DOR agonists. [source] Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic painFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2007Sameer Sharma Abstract Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor- , (TNF- ,) and whole brain nitric oxide (NO) release. Four weeks after a single intraperitoneal injection of streptozotocin (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights when compared with control mice. Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF- , levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain. [source] Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factorJOURNAL OF NEUROCHEMISTRY, Issue 1 2007Qing Xue Abstract The capsaicin receptor, also known as ,transient receptor potential vanilloid receptor subtype 1' (TRPV1, VR1), is an ion channel subunit expressed in primary afferent nociceptors, which plays a critical role in pain transduction and thermal hyperalgesia. Increases in nociceptor TRPV1 mRNA and protein are associated with tissue injury,inflammation. As little is understood about what controls TRPV1 RNA transcription in nociceptors, we functionally characterized the upstream portion of the rat TRPV1 gene. Two functional rTRPV1 promoter regions and their transcription initiation sites were identified. Although both promoter regions directed transcriptional activity in nerve growth factor (NGF) treated rat sensory neurons, the upstream Core promoter was the most active in cultures enriched in sensory neurons. Because NGF is a key modulator of inflammatory pain, we examined the effect of NGF on rTRPV1 transcription in PC12 cells. NGF positively regulated transcriptional activity of both rTRPV1 promoter regions in PC12 cells. We propose that the upstream regulatory region of the rTRPV1 gene is composed of a dual promoter system that is regulated by NGF. These findings support the hypothesis that NGF produced under conditions of tissue injury and/or inflammation directs an increase of TRPV1 expression in nociceptors in part through a transcription-dependent mechanism. [source] The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis modelsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008Suk-Yun Kang Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25,200 mg kg,1) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE2) production in the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg,1 in the zymosan experiment, we used this dose of UA in a subsequent study using an adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg,1, per oral, once a day for 10 days) was started from day 12 after adjuvant injection. UA dramatically inhibited paw swelling, plasma PGE2 production and radiological changes in the joint caused by CFA injection. Moreover, UA significantly suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as the spinal Fos expression, as determined by immunohistochemistry, which was increased by CFA injection. In addition, overall anti-arthritic potency of UA was comparable with ibuprofen (100 mg kg,1, oral) while UA did not induce significant gastric lesions as compared with the ibuprofen treatment group. These findings strongly suggest that UA is a useful suppressive compound for rheumatoid arthritis treatment with low risk of gastric problems. [source] Microinjection of morphine into thalamic nucleus submedius depresses bee venom-induced inflammatory pain in the ratJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2008Jie Feng Previous studies have provided evidence of the existence of a pain modulatory feedback pathway consisting of thalamic nucleus submedius (Sm),ventrolateral orbital cortex-periaqueductal grey pathway, which is activated during acute pain and leads to depression of transmission of nociceptive information in the spinal dorsal horn. The aim of this study was to test the hypothesis that morphine microinjection into the Sm decreased spontaneous pain and bilateral thermal hyperalgesia, as well as ipsilateral mechanical allodynia, induced by subcutaneous injections of bee venom into the rat hind paw. Morphine (1.0, 2.5 or 5.0 m,g in 0.5 ,L) injected into the Sm, contralateral to the bee venominjected paw, depressed spontaneous nociceptive behaviour in a dose-dependent manner. Furthermore, morphine significantly decreased bilateral thermal hyperalgesia and ipsilateral mechanical allodynia 2 h after bee venom injection. These morphine-induced effects were antagonized by 1.0 ,g naloxone (an opioid antagonist) microinjected into the Sm 5 min before morphine administration. The results provided further support for the important role of the Sm and Sm-opioid receptors in inhibiting nociceptive behaviour and indicated for the first time that Sm opioid receptors were also effective in inhibiting the hypersensitivity provoked by bee venom-induced inflammation. [source] Sciatic inflammatory neuritis (SIN): Behavioral allodynia is paralleled by peri-sciatic proinflammatory cytokine and superoxide productionJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2001Lawrence S. Gazda Abstract We have recently developed a model of sciatic inflammatory neuritis (SIN) to assess how immune activation near peripheral nerves influences somatosensory processing. Administration of zymosan (yeast cell walls) around a single sciatic nerve produces dose-dependent low-threshold mechanical allodynia without thermal hyperalgesia. Low (4 ,g) doses produce both territorial and extraterritorial allodynia restricted to the injected hindleg. In contrast, higher (40 ,g) doses produce territorial and extraterritorial allodynias of both hindlegs, an effect not accounted for by systemic spread of the zymosan. The aim of these experiments was to determine whether these behavioral allodynias were correlated with immunological and/or anatomical changes in or around the sciatic nerve. These experiments reveal that zymosan-induced bilateral allodynia was associated with the following: (a) increased release of both interleukin-1, and tumor necrosis factor-, from peri-sciatic immune cells; (b) increased release of reactive oxygen species from peri-sciatic immune cells; (c) no change in circulating levels of proinflammatory cytokine; (d) no apparent zymosan-induced influx of immune cells into the sciatic nerve from the endoneurial blood vessels; (e) mild edema of the sciatic, which was predominantly restricted to superficial regions closest to the peri-sciatic immune cells; and (f) no anatomic evidence of changes in either the ipsilateral saphenous nerve or contralateral sciatic nerve that could account for the appearance of extraterritorial or contralateral ("mirror") allodynia, respectively. No reliable differences were found when the low-dose zymosan was compared with vehicle controls. Taken together, these data suggest that substances released by peri-sciatic immune cells may induce changes in the sciatic nerve, leading to the appearance of bilateral allodynia. [source] Etanercept reduces hyperalgesia in experimental painful neuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2001Claudia Sommer Abstract Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain. [source] Effects Of Topically Applied Capsaicin Cream On Neurogenic Inflammation And Thermal Sensitivity In RatsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2000M. Yoshimura The effects of capsaicin cream on neurogenic inflammation and thermal nociceptive threshold were investigated in rats. Firstly, for topical application of capsaicin cream to hind paw, we shaped boots from dental cement to prevent the animals from licking off the drug. Capsaicin cream (1%) led to significant increases in the amounts of Evans blue and substance P (SP) released into the perfusate, and the former response was significantly suppressed by pretreatment with RP67580, an NK1-receptor antagonist, but not by treatment with an NK2-receptor antagonist. Subsequent electrical stimulation of the sciatic nerve resulted in a significant reduction in Evans blue and SP extravasation 24 h after topical application of capsaicin cream. On the other hand, when capsaicin cream was repeatedly applied to both hind paws once a day, withdrawal latency for noxious heat stimulation decreased after 24 h, and this thermal hyperalgesia was reversed 3 days later. These results suggest that capsaicin cream initially affects neurogenic inflammation mechanisms and then blocks the pain transmission mechanism. [source] Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic ratPHYTOTHERAPY RESEARCH, Issue 8 2010Tourandokht Baluchnejadmojarad Abstract The effect of chronic silymarin (SM) treatment on hyperalgesia, sciatic motor nerve conduction velocity (MNCV) and oxidative stress in streptozotocin (STZ)-diabetic neuropathic rat was evaluated. Rats were divided into control, diabetic, SM-treated control and diabetic, and sodium salisylate (SS)-treated control and diabetic. SM was administered daily at a dose of 100,mg/kg for two months. Finally, hyperalgesia and sciatic MNCV and oxidative stress markers were assessed. Diabetic rats showed a significant deficit in MNCV and markedly exhibited chemical and thermal hyperalgesia, indicating development of diabetic neuropathy. Antioxidant enzyme superoxide dismutase (SOD) level significantly reduced and malondialdehyde (MDA) level significantly increased in diabetic rats compared to control rats; SM treatment significantly ameliorated the alteration in MNCV, hyperalgesia, MDA level and antioxidant enzyme SOD in diabetic rats. These results clearly suggest the potential effect of SM in prevention and treatment of diabetic neuropathy. Copyright © 2009 John Wiley & Sons, Ltd. [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] C-peptide prevents nociceptive sensory neuropathy in type 1 diabetesANNALS OF NEUROLOGY, Issue 6 2004Hideki Kamiya MD We examined the effects of C-peptide replacement on unmyelinated fiber function in the hind paw, sural nerve C-fiber morphometry, sciatic nerve neurotrophins, and the expression of neurotrophic receptors and content of neuropeptides in dorsal root ganglia in type 1 diabetic BB/Wor-rats. C-peptide replacement from onset of diabetes had no effect on hyperglycemia, but it significantly prevented progressive thermal hyperalgesia and prevented C-fiber atrophy, degeneration, and loss. These findings were associated with preventive effects on impaired availability of nerve growth factor and neurotrophin 3 in the sciatic nerve and significant prevention of perturbed expression of insulin, insulin growth factor,1, nerve growth factor, and neurotrophin 3 receptors in dorsal root ganglion cells. These beneficial effects translated into prevention of the decreased content of dorsal root ganglia nociceptive peptides such as substance P and calcitonin gene,related peptide. From these findings we conclude that replacement of insulinomimetic C-peptide prevents abnormalities of neurotrophins, their receptors, and nociceptive neuropeptides in type 1 BB/Wor-rats, resulting in the prevention of C-fiber pathology and nociceptive sensory nerve dysfunction. The data indicate that perturbed insulin/C-peptide action plays an important pathogenetic role in nociceptive sensory neuropathy and that C-peptide replacement may be of benefit in treating painful diabetic neuropathy in insulin-deficient diabetic conditions. Ann Neurol 2004 [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] In vivo evidence for a role of protein kinase C in peripheral nociceptive processingBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2002Adriano L S Souza The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). Intraplantar injection of phorbol-12,13-didecanoate (PDD; 0.01, 0.1 or 1 ,g), a PKC activator, but not of 4,-PDD (inactive analogue), dose-dependently induced thermal hyperalgesia in rats. This response was not observed at the contralateral hindpaw. Intraplantar injection of PDD (0.01, 0.1 or 1 ,g) also induced mechanical allodynia. In mice, injection of PDD (0.1 or 1 ,g) into the dorsum of the hindpaw induced a spontaneous licking behaviour. Intraplantar co-injection of chelerythrine (10 or 50 ,g), a PKC inhibitor, attenuated the thermal hyperalgesia induced by PDD (0.1 ,g) in rats. The second phase of the nociceptive response induced by the injection of formaldehyde (0.92%, 20 ,l) into the dorsum of mice hindpaws was inhibited by ipsi-, but not contralateral, pre-treatment with chelerythrine (1 ,g). Intraplantar injection of BK (10 ,g) induced mechanical allodynia in rats. Ipsi- but not contralateral injection of bisindolylmaleimide I (10 ,g), a PKC inhibitor, inhibited BK-induced mechanical allodynia. In conclusion, this study demonstrates that PKC activation at peripheral tissues leads to the development of spontaneous nociceptive response, thermal hyperalgesia and mechanical allodynia. Most importantly, it also gives in vivo evidence that peripheral PKC activation is essential for the full establishment of the nociceptive response induced by two different inflammatory stimuli. British Journal of Pharmacology (2002) 135, 239,247; doi:10.1038/sj.bjp.0704434 [source] | ||||||||||||||||||||||