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Allodynia
Kinds of Allodynia Selected AbstractsAllodynia in Migraine: Association With Comorbid Pain ConditionsHEADACHE, Issue 9 2009Gretchen E. Tietjen MD Background., Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. Methods., Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. Results., A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported ,4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. Conclusion., Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings. [source] Almotriptan Efficacy in Migraine With Developing Allodynia Is as High as the Efficacy in Migraine Without Allodynia , But Is It the Same in Migraine With Established Allodynia?HEADACHE, Issue 3 2009Rami Burstein PhD No abstract is available for this article. [source] Change of Excitability in Brainstem and Cortical Visual Processing in Migraine Exhibiting AllodyniaHEADACHE, Issue 10 2006Koichi Shibata MD Background.,Clinical and neurophysiological manifestations of information processing associated with central sensitization are little known. Allodynic migraine (AM) can be caused by the sensitization of trigeminal neuron, but no study has reported on AM between attacks using blink reflex (BR) and pattern-reversal visual evoked potentials (PVEPs). Objective.,We explored the characteristics of AM between attacks associated with central sensitization using BR and PVEP. Methods.,We recruited 13 patients with interictal AM and 15 patients with nonallodynic migraine (NA), and 30 healthy subjects (HS). BRs were obtained using paired pulses delivered at the interstimulus interval (ISI) of 150, 300, and 500 ms. The ratio of the area in the R2 of the second to R2 of the first shock was measured for each ISI. PVEP were recorded with 2 spatial frequencies (0.5 and 4.0 cpd) and 2 low and high contrasts (29% and 98%, respectively). Amplitudes of P100 were measured. Results.,For BR, there were no significant differences in the ratio of the area of the R2 between the sides of stimulation, and the sides of headache. AM patients had less suppression of the R2 at the ISI of 150 and 300 ms when compared with the NA patients and HS. For PVEP, at 0.5, there were significant differences of amplitude between AM patients and HS, and between NA patients and HS in low and high contrast. At 4.0 cpd, there were significant differences of amplitude between AM patients and HS in low contrast, and between AM patients and HS, and NA patients and HS in high contrast. In AM patients, there was a significant difference of amplitude ratio between 0.5 and 4.0 cpd. Conclusions.,Our BR and PVEP study showed that migraine patients exhibiting allodynia may show central sensitization of brainstem trigeminal neuron and have contrast modulating dysfunction during the cortical visual processing of striate and extrastriate on visual cortex in-between attacks. [source] The Effect of Menthol on Cold Allodynia in Patients with Neuropathic PainPAIN MEDICINE, Issue 3 2008Gunnar Wasner MD ABSTRACT Objective., Cutaneous application of menthol in healthy subjects induces cold allodynia via sensitization of cold-sensitive nociceptors. We investigated the effects of menthol on preexisting cold allodynia in patients to test whether the allodynia was exacerbated. Design., In eight neuropathic pain patients (six of peripheral, two of central origin), 40% menthol was applied topically to an area of preexisting cold allodynia. Mirror-image skin areas and aged-matched healthy subjects served as controls in patients with unilateral and bilateral neuropathic pain, respectively. Prior to and after menthol, cold pain thresholds were measured using a thermotest device. Results., Menthol induced significant cold allodynia in control areas. However, in neuropathic areas, results were more heterogeneous. Overall, preexisting cold allodynia was not aggravated by topical menthol and was attenuated in 6/8 patients. Conclusions., These results suggest that, unlike in controls, menthol is not more hyperalgesic, but may be analgesic in some patients with peripheral and central neuropathic pain. [source] A Severe Case of Complex Regional Pain Syndrome I (Reflex Sympathetic Dystrophy) Managed with Spinal Cord StimulationPAIN PRACTICE, Issue 1 2010Bernard Canlas MD Abstract Complex regional pain syndrome is a condition that usually affects the upper or lower extremities. The cause is not clearly understood. We report a case of a severe form of a rapidly progressive complex regional pain syndrome type I developing after a right shoulder injury managed with spinal cord stimulation (SCS). After failed conservative treatments, a rechargeable SCS system was implanted in the cervical spine. Allodynia and dystonia improved but the patient subsequently developed similar symptoms in lower right extremity followed by her lower left extremity. The patient became wheelchair bound. A second rechargeable SCS with a paddle electrode was implanted for the lower extremity coverage. The patient's allodynia and skin lesions improved significantly. However, over time, her initial symptoms reappeared which included skin breakdown. Due to the need for frequent recharging, the system was removed. During explantation of the surgical paddle lead, it was noted by the neurosurgeon that the contacts of the paddle lead were detached from the lead. After successful implantation of another SCS system, the patient was able to reduce her medications and is now able to ambulate with the use of a left elbow crutch. [source] Reduction of Allodynia by Intrathecal Transplantation of Microencapsulated Porcine Chromaffin CellsARTIFICIAL ORGANS, Issue 3 2009Yu Mi Kim Abstract Bovine chromaffin cells (BCCs) are well known to have analgesic effect to reduce acute or chronic pain when transplanted in the subarachnoid space and have been considered as an alternative therapy for pain management. However, due to recent concerns over risks associated with prion transmission, porcine tissue is considered to be an alternate xenogeneic source for clinical use. In the present study, we investigated whether microencapsulated porcine adrenal medullary chromaffin cells (PCCs) also have analgesic effect to reduce allodynia caused by neuropathic pain in chronic constriction injury model of rat. PCCs were isolated from a porcine adrenal medulla and then microencapsulated with alginate and poly. In in vitro tests, the microencapsulated PCCs were investigated whether they have an ability to release catecholamines responding to nicotine stimulation. The levels of catecholamines released from the microencapsulated PCCs were significantly higher than from microencapsulated BCCs. In addition, the microencapsulated PCCs released catecholamines and met-enkephalin responding to cerebral spinal fluid (CSF) retrieved from a neuropathic pain model. In in vivo tests, implantation of microencapsulated PCCs reduced both mechanical and cold allodynia in chronic constriction injury model of a rat whereas the microencapsulated BCCs reduced only cold allodynia under the same conditions. The injection of antagonist of opioid peptides reversed the reduction of cold allodynia in microencapsulated PCC-received animal. The levels of catecholamines in the CSF of rats after implantation of microencapsulated PCCs were significantly higher than in the control group. These data suggest that microencapsulated PCCs may be another effective source for the treatment of neuropathic pain. [source] Immunoisolated Chromaffin Cells Implanted Into the Subarachnoid Space of Rats Reduce Cold Allodynia in a Model of Neuropathic Pain: A Novel Application of Microencapsulation TechnologyARTIFICIAL ORGANS, Issue 12 2004Yu Mi Kim Abstract:, Intrathecal transplants of adrenal medullary chromaffin cells relieve chronic pain by secreting catecholamines, opioids, and other neuroactive substances. Recently, macrocapsules with semipermeable membranes were used to isolate immunologically xenogenic chromaffin cells, but the poor viability in vivo of the encapsulated chromaffin cells limited the usefulness of this method. In this study, we used a novel method of encapsulation to increase the viability of chromaffin cells. We found that microencapsulated chromaffin cells that were implanted into the subarachnoid space of rats relieved cold allodynia in a model of neuropathic pain. Furthermore, microencapsulated chromaffin cells were morphologically normal and retained their functionality. These findings suggest that the intrathecal placement of microencapsulated chromaffin cells might be a useful method for treating chronic pain. [source] Thermal pain thresholds are decreased in the migraine preattack phaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2008T. Sand Background and purpose:, Migraine patients may have cutaneous allodynia during attacks. In order to investigate if pain physiology changes in the preattack phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on three different days in 41 migraine patients and 28 controls. Methods:, A thermode was applied at four sites bilaterally: forehead, face, neck, and hand. A subgroup of 11 migraine patients had been tested within 24 h before their next attack and in the interictal phase. Results:, In the preattack phase, HPT was lower compared with the paired interictal recording for the hand (44.8°C vs. 45.9°C, P = 0.009), neck (46.8°C vs. 48.2°C, P = 0.02), and forehead (45.1°C vs. 46.3°C, P = 0.02). Neck and hand CPT were higher in the preattack phase than interictally (10°C vs. 7.3°C, P = 0.01 and 11.6°C vs. 9.4°C, P = 0.06, respectively). Preattack forehead changes were most apparent on the headache side of the subsequent attack. Discussion:, Subclinical preattack thermal pain hypersensitivity seems to be a feature of the process that leads to a migraine attack. [source] Neuronal disinhibition in the trigeminal nucleus caudalis in a model of chronic neuropathic painEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2010Yasmina B. Martin Abstract The mechanisms underlying neuropathic facial pain syndromes are incompletely understood. We used a unilateral chronic constriction injury of the rat infraorbital nerve (CCI-IoN) as a facial neuropathic model. Pain-related behavior of the CCI-IoN animals was tested at 8, 15 and 26 days after surgery (dps). The response threshold to mechanical stimulation with von Frey hairs on the injured side was reduced at 15 and 26 dps, indicating the presence of allodynia. We performed unitary recordings in the caudalis division of the spinal trigeminal nucleus (Sp5C) at 8 or 26 dps, and examined spontaneous activity and responses to mechanical and thermal stimulation of the vibrissal pad. Neurons were identified as wide dynamic range (WDR) or low-threshold mechanoreceptive (LTM) according to their response to tactile and/or noxious stimulation. Following CCI-IoN, WDR neurons, but not LTM neurons, increased their spontaneous activity at 8 and 26 dps, and both types of Sp5C neurons increased their responses to tactile stimuli. In addition, the on,off tactile response in neurons recorded after CCI-IoN was followed by afterdischarges that were not observed in control cases. Compared with controls, the response inhibition observed during paired-pulse stimulation was reduced after CCI-IoN. Immunohistochemical studies showed an overall decrease in GAD65 immunoreactivity in Sp5C at 26 dps, most marked in laminae I and II, suggesting that following CCI-IoN the inhibitory circuits in the sensory trigeminal nuclei are depressed. Consequently, our results strongly suggest that disinhibition of Sp5C neurons plays a relevant role in the appearance of allodynia after CCI-IoN. [source] Sensitization of meningeal nociceptors: inhibition by naproxenEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Dan Levy Abstract Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of A,- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N -[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of A,- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. [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] Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5GENES, BRAIN AND BEHAVIOR, Issue 2 2007K.-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] Activation of dorsal horn microglia contributes to diabetes-induced tactile allodynia via extracellular signal-regulated protein kinase signalingGLIA, Issue 4 2008Makoto Tsuda Abstract Painful neuropathy is one of the most common complications of diabetes, one hallmark of which is tactile allodynia (pain hypersensitivity to innocuous stimulation). The underlying mechanisms of tactile allodynia are, however, poorly understood. Emerging evidence indicates that, following nerve injury, activated microglia in the spinal cord play a crucial role in tactile allodynia. However, it remains unknown whether spinal microglia are activated under diabetic conditions and whether they contribute to diabetes-induced tactile allodynia. In the present study, using streptozotocin (STZ)-induced diabetic rats that displayed tactile allodynia, we found several morphological changes of activated microglia in the dorsal horn. These included increases in Iba1 and OX-42 labeling (markers of microglia), hypertrophic morphology, the thickness and the retraction of processes, and in the number of activated microglia cells. Furthermore, in the dorsal horn of STZ diabetic rats, extracellular signal-regulated protein kinase (ERK) and an upstream kinase, Src-family kinase (SFK), both of which are implicated in microglial functions, were activated exclusively in microglia. Moreover, inhibition of ERK phosphorylation in the dorsal horn by intrathecal administration of U0126, an inhibitor of ERK activation, produced a striking alleviation of existing, long-term tactile allodynia of diabetic rats. We also found that a single administration of U0126 reduced the expression of allodynia. Together, these results suggest that activated dorsal horn microglia may be a crucial component of diabetes-induced tactile allodynia, mediated, in part, by the ERK signaling pathway. Thus, inhibiting microglia activation in the dorsal horn may represent a therapeutic strategy for treating diabetic tactile allodynia. © 2008 Wiley-Liss, Inc. [source] Childhood Maltreatment and Migraine (Part II).HEADACHE, Issue 1 2010Emotional Abuse as a Risk Factor for Headache Chronification (Headache 2010;50:32-41) Objectives., To assess in a headache clinic population the relationship of childhood abuse and neglect with migraine characteristics, including type, frequency, disability, allodynia, and age of migraine onset. Background., Childhood maltreatment is highly prevalent and has been associated with recurrent headache. Maltreatment is associated with many of the same risk factors for migraine chronification, including depression and anxiety, female sex, substance abuse, and obesity. Methods., Electronic surveys were completed by patients seeking treatment in headache clinics at 11 centers across the United States and Canada. Physician-determined data for all participants included the primary headache diagnoses based on the International Classification of Headache Disorders-2 criteria, average monthly headache frequency, whether headaches transformed from episodic to chronic, and if headaches were continuous. Analysis includes all persons with migraine with aura, and migraine without aura. Questionnaire collected information on demographics, social history, age at onset of headaches, migraine-associated allodynic symptoms, headache-related disability (The Headache Impact Test-6), current depression (The Patient Health Questionnaire-9), and current anxiety (The Beck Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual, emotional, and physical) and neglect (emotional and physical) was gathered using the Childhood Trauma Questionnaire. Results., A total of 1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and chronic headache (,15 days/month) was reported by 34%. Transformation from episodic to chronic was reported by 26%. Prevalence of current depression was 28% and anxiety was 56%. Childhood maltreatment was reported as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. In univariate analyses, physical abuse and emotional abuse and neglect were significantly associated with chronic migraine and transformed migraine. Emotional abuse was also associated with continuous daily headache, severe headache-related disability, and migraine-associated allodynia. After adjusting for sociodemographic factors and current depression and anxiety, there remained an association between emotional abuse in childhood and both chronic (odds ratio [OR] = 1.77, 95% confidence intervals [CI]: 1.19-2.62) and transformed migraine (OR = 1.89, 95% CI: 1.25-2.85). Childhood emotional abuse was also associated with younger median age of headache onset (16 years vs 19 years, P = .0002). Conclusion., Our findings suggest that physical abuse, emotional abuse, and emotional neglect may be risk factors for development of chronic headache, including transformed migraine. The association of maltreatment and headache frequency appears to be independent of depression and anxiety, which are related to both childhood abuse and chronic daily headache. The finding that emotional abuse was associated with an earlier age of migraine onset may have implications for the role of stress responses in migraine pathophysiology. [source] Allodynia in Migraine: Association With Comorbid Pain ConditionsHEADACHE, Issue 9 2009Gretchen E. Tietjen MD Background., Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. Methods., Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. Results., A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported ,4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. Conclusion., Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings. [source] Change of Excitability in Brainstem and Cortical Visual Processing in Migraine Exhibiting AllodyniaHEADACHE, Issue 10 2006Koichi Shibata MD Background.,Clinical and neurophysiological manifestations of information processing associated with central sensitization are little known. Allodynic migraine (AM) can be caused by the sensitization of trigeminal neuron, but no study has reported on AM between attacks using blink reflex (BR) and pattern-reversal visual evoked potentials (PVEPs). Objective.,We explored the characteristics of AM between attacks associated with central sensitization using BR and PVEP. Methods.,We recruited 13 patients with interictal AM and 15 patients with nonallodynic migraine (NA), and 30 healthy subjects (HS). BRs were obtained using paired pulses delivered at the interstimulus interval (ISI) of 150, 300, and 500 ms. The ratio of the area in the R2 of the second to R2 of the first shock was measured for each ISI. PVEP were recorded with 2 spatial frequencies (0.5 and 4.0 cpd) and 2 low and high contrasts (29% and 98%, respectively). Amplitudes of P100 were measured. Results.,For BR, there were no significant differences in the ratio of the area of the R2 between the sides of stimulation, and the sides of headache. AM patients had less suppression of the R2 at the ISI of 150 and 300 ms when compared with the NA patients and HS. For PVEP, at 0.5, there were significant differences of amplitude between AM patients and HS, and between NA patients and HS in low and high contrast. At 4.0 cpd, there were significant differences of amplitude between AM patients and HS in low contrast, and between AM patients and HS, and NA patients and HS in high contrast. In AM patients, there was a significant difference of amplitude ratio between 0.5 and 4.0 cpd. Conclusions.,Our BR and PVEP study showed that migraine patients exhibiting allodynia may show central sensitization of brainstem trigeminal neuron and have contrast modulating dysfunction during the cortical visual processing of striate and extrastriate on visual cortex in-between attacks. [source] Neurochemistry of Trigeminal Activation in an Animal Model of MigraineHEADACHE, Issue 2006Michael L. Oshinsky PhD Research techniques such as electrophysiology, cFos protein expression, and other measurements of neuronal activation provide insights into the pathophysiology of pain processing in migraine, but they do not indicate the specific neurotransmitter systems involved. This paper summarizes data from microdialysis experiments in which changes in the neurochemistry of the trigeminal nucleus caudalis (TNC) were monitored during dural stimulation. Microdialysis allows the measurement of extracellular concentrations of neurotransmitters in a small area of the brain, in vivo, by means of a probe equipped with a semipermeable membrane. Microdialysis enables direct measurement of changes in extracellular concentrations of neurotransmitters in the intact animal over time in response to dural inflammation. Following the activation of the dural nociceptors, changes in the extracellular amino acid neurotransmitters in the deep lamina of the TNC were tracked. A 5-minute application of inflammatory soup when compared with saline to the dura of rats induced a transient decrease in extracellular glutamate in the TNC at approximately 30 minutes postapplication. This short-lived decrease was followed by a continuous increase in extracellular glutamate to a level of approximately 3 times the baseline value at 3 hours after application of the inflammatory soup. The time course of this increase in extracellular glutamate correlated with changes in sensory thresholds on the face of the rat from electrophysiological recordings of secondary sensory neurons in the TNC. No significant differences between the inflammatory soup and saline conditions were observed for extracellular concentrations of aspartate (an excitatory amino acid) or the inhibitory neurotransmitters gamma-aminobutyric acid or glutamine. Results of these experiments support an integral role for glutamate in central sensitization of neurons in the TNC, and suggest an important contribution of glutamate to allodynia and hyperalgia in this animal model of migraine. [source] Improved outcome of EAN, an animal model of GBS, through amelioration of peripheral and central inflammation by minocyclineJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2009Zhi-Yuan Zhang Abstract Experimental autoimmune neuritis (EAN) is a widely used animal model of the human acute inflammatory demyelinating polyradiculoneuropathy, which is the most common subtype of Guillain-Barré Syndrome. EAN is pathologically characterized by breakdown of the blood-nerve barrier, infiltration of reactive immune cells, local inflammation, demyelination in the peripheral nervous system and mechanical allodynia. Minocycline is known to have neuroprotective and anti-inflammatory effects. Furthermore, relieve of neuropathic pain following minocycline administration was observed in a variety of animal models. Here, we investigated the effects of minocycline on rat EAN. Suppressive treatment with minocycline (50 mg/kg body weight daily immediately after immunization) significantly attenuated the severity and duration of EAN. Macrophage and T-cell infiltration and demyelination in sciatic nerves of EAN rats treated with minocycline were significantly reduced compared to phosphate-buffered saline (PBS)-treated EAN rats. mRNA expressions of matrix metallopeptidase-9, inducible nitric oxide synthase and pro-inflammatory cytokines interleukin-1 , and tumour necrosis factor-, in EAN sciatic nerves were greatly decreased by administration of minocycline as well. Furthermore, minocycline attenuated mechanical allodynia in EAN rats and greatly suppressed spinal microglial activation. All together, our data showed that minocycline could effectively suppress the peripheral and spinal inflammation (immune activation) to improve outcome in EAN rats, which suggests that minocycline may be considered as a potential candidate of pharmacological treatment for autoimmune-mediated neuropathies. [source] Consequences of altered eicosanoid patterns for nociceptive processing in mPGES-1-deficient miceJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2008Christian Brenneis Abstract Cyclooxygenase-2 (COX-2)-dependent prostaglandin (PG) E2 synthesis in the spinal cord plays a major role in the development of inflammatory hyperalgesia and allodynia. Microsomal PGE2 synthase-1 (mPGES-1) isomerizes COX-2-derived PGH2 to PGE2. Here, we evaluated the effect of mPGES-1-deficiency on the noci-ceptive behavior in various models of nociception that depend on PGE2 synthesis. Surprisingly, in the COX-2-dependent zymosan-evoked hyperalgesia model, the nociceptive behavior was not reduced in mPGES-1-deficient mice despite a marked decrease of the spinal PGE2 synthesis. Similarly, the nociceptive behavior was unaltered in mPGES-1-deficient mice in the formalin test. Importantly, spinal cords and primary spinal cord cells derived from mPGES-1-deficient mice showed a redirection of the PGE2 synthesis to PGD2, PGF2, and 6-keto-PGF1, (stable metabolite of PGI2). Since the latter prostaglandins serve also as mediators of noci-ception they may compensate the loss of PGE2 synthesis in mPGES-1-deficient mice. [source] Sensory function and pain in a population of patients treated for breast cancerACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009O. J. VILHOLM Background: Chronic pain is often reported after surgery for breast cancer. This study examined pain and sensory abnormalities in women following breast cancer surgery. Methods: Sensory tests were carried out on the operated and contra-lateral side in 55 women with chronic pain after breast cancer treatment and in a reference group of 27 pain-free women, who had also undergone treatment for breast cancer. Testing included a numeric rating score of spontaneous pain, detection and pain threshold to thermal and dynamic mechanical stimuli and temporal summation to repetitive pinprick stimulation. The neuropathic pain symptom inventory was applied for participants with chronic pain. Results: The mean age was 58.6 years for the pain patients and 60.6 years for the pain-free patients. Thermal thresholds were significantly higher on the operated side than on the contra-lateral side in both groups and side difference in warmth detection threshold was significantly higher in the pain group than in the pain-free group (mean 3.8 °C vs. 1.1 °C, P=0.01). The frequency of cold allodynia was higher in participants with pain than in pain-free participants (15/53 vs. 1/25, P=0.01), and the frequency of temporal summation evoked by repetitive pinprick was higher in participants with pain than in pain-free participants (23/53 vs. 2/25, P=0.0009). The frequency of dynamic mechanical allodynia did not differ significantly between the two groups. Conclusion: These findings suggest that chronic pain after surgery for breast cancer is associated with sensory hyperexcitability and is a neuropathic pain condition. [source] Reactive oxygen species in rats with chronic post-ischemia painACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009K. H. KWAK Background: An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw. Methods: Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague,Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N -nitro- l -arginine methyl ester (l -NAME, 10 mg/kg), or SOD (4000 U/kg)+l -NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats. Results: Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and l -NAME, which were used to investigate the roles of superoxide (O2 ,,) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks. Conclusions: Our findings suggest that O2 ,, and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects. [source] Functional characterization of prostaglandin F2, receptor in the spinal cord for tactile pain (allodynia)JOURNAL OF NEUROCHEMISTRY, Issue 2 2003Tadatoshi Muratani Abstract Prostaglandin F2, (PGF2,) binds to its receptor (FP) to increase the intracellular-free calcium concentration ([Ca2+]i) by coupling of FP with Gq protein. Spinal intrathecal administration of PGF2, to mouse induces touch-evoked pain (mechanical allodynia), in which capsaicin-insensitive primary afferent A,-fibres and N -methyl- d -aspartate receptor ,4 subunit are involved. FP in the spinal cord, however, was not well characterized. Here, we showed constitutive expression of FP mRNA in mouse spinal cord, and functionally characterized spinal FP-expressing cells which were involved in PGF2, -induced mechanical allodynia. The method for repetitive administration of oligodeoxyribonucleotides through tubing to conscious mice was established for mechanical allodynia evaluation. We identified an antisense oligodeoxyribonucleotide targeting FP mRNA, causing both disappearance of PGF2, -induced mechanical allodynia and decrease of FP mRNA. With saline-administered mice, PGF2, rapidly increased [Ca2+]i of the cells in the deeper layer of the dorsal horn. In contrast, when the FP antisense oligodeoxyribonucleotide was repeatedly administered, the population of PGF2, -responsive cells in the slices reduced, and PGF2, -induced [Ca2+]i increase of these cells diminished. These data strongly suggested that, in the dorsal horn of the spinal cord, there are the FP-expressing cells which are involved in PGF2, -induced mechanical allodynia. [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] Differential activation of C1 complement components in rat spinal cord after sciatic nerve injuryJOURNAL OF NEUROCHEMISTRY, Issue 2003J. Mika Neuroimmune interactions are discussed to drive neuropathic pain. We used the Bennett model to correlate pain and cellular expression profiles of the complement factors C1q and C1q-associated serine proteases C1r/C1s in lumbar spinal cord. At 2 days C1q mRNA levels increased ipsilateral to the lesion, and peaked at 8 days when allodynia and severe walking problems were present. During regeneration walking problems disappeared together with C1q mRNA levels. C1q biosynthesis was restricted to microglia. Surprisingly, C1s/C1r biosynthesis was not increased after injury suggesting a role for C1q different from classical complement activation. Sustained C1q expression in spinal microglia after lesion in conjunction with pain behavior indicates that microglial C1q may be causally involved in the development and maintenance of neuropathic pain. Acknowledgements:, Supported by BMBF01GG9818, SFB297, DFGWE910/8-3, KBN3P05C00623. [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] Blockade of the 5-HT3 receptor for days causes sustained relief from mechanical allodynia following spinal cord injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2009Yuhua Chen Abstract Chronic neuropathic pain is a frequent, serious outcome of spinal cord injury (SCI) that is highly refractory to treatment. Serotonin can contribute to neuropathic pain after SCI, as suggested by our previous observation that transient blockade of the 5-HT3 receptor by intrathecal injections of the antagonist ondansetron reduces mechanical allodynia after SCI in rats. The current study determined whether intrathecal or intravenous infusion of ondansetron for 3 or 7 days, respectively, could cause sustained blockade of mechanical allodynia at and below the level of a twelfth thoracic clip compression injury in rats. Intrathecal 3-day infusion of ondansetron (2.0 ,g/hr), targeted to the cord rostral to the SCI and commencing at 28 days after SCI, decreased at-level mechanical allodynia by 40% and below-level allodynia by 60% compared with saline-treated rats (controls). This reduction was sustained throughout drug delivery and for 1 day afterward. During the next 3 days, allodynia gradually returned toward the values of saline-treated rats. An initial experiment showed that bolus intravenous injections of ondansetron (20,100 ,g) at 28 days after SCI decreased both at- and below-level allodynia for 90,120 min. Intravenous 7-day infusions (20 ,g/hr), commencing at 28 days after SCI, significantly decreased at-level allodynia by 48% and below-level allodynia by 51% compared with controls. This reduction of allodynia lasted throughout the infusion and for 1,3 days afterward while pain responses gradually approached those of controls. These findings suggest a potential role of 5-HT3 receptor antagonism in the relief of neuropathic pain after SCI in humans. © 2008 Wiley-Liss, Inc. [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] A MOUSE MODEL FOR PERIPHERAL NEUROPATHY PRODUCED BY A PARTIAL INJURY OF THE NERVE SUPPLYING THE TAILJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002SK Back We attempted to develop a mouse model for peripheral neuropathy by a partial injury of the nerve supplying the tail. Under enflurane anesthesia, the unilateral superior caudal trunk was resected between the S3 and S4 spinal nerves. Tests for thermal allodynia were conducted by immersing the tail into 4 or 38°C water. The mechanical allodynia was assessed by stimulating the tail with a von Frey hair (1.96 mN, 0.2 g). After the nerve injury, the experimental animals had shorter tail withdrawal latencies to cold and warm water immersion than the presurgical latency, and exhibited an increase in tail response to von Frey stimulation. We interpret these abnormal sensitivities as the signs of mechanical, cold and warm allodynia following the superior caudal trunk injury in the mouse. [source] Response Characteristics Of Cutaneous Mechanoreceptors In Neuropathic RatsJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2002A Bulka The activity of single myelinated afferents was recorded from dorsal roots L4-5 in normal Sprague-Dawley rats and animals that developed mechanical hypersensitivity following ischemic injury to the sciatic nerve. The mechanical response properties and conduction velocity of afferents conducting through the injury site (about 50% of units) were similar to controls. However, the majority of afferents not conducting through the injury site exhibited ongoing activity. The results suggest that mechanical allodynia may be at least partly due to the central integration of activity arising from these two populations of afferents in neuropathic rats. [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] | |||||||||||||||||||||||||||||||||||||