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Z Wiesenfeldhallin - One of the best experts on this subject based on the ideXlab platform.
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Flexor Reflex excitability in mice lacking galanin receptor galanin r1
Neuroscience Letters, 2003Co-Authors: Stefan Grass, Xiao-jun Xu, Arie S Jacoby, Tiina P Iismaa, Jacqueline N Crawley, Z WiesenfeldhallinAbstract:Abstract This study was conducted to examine the excitability of the nociceptive Flexor Reflex and its sensitization by repetitive stimulation of C-fibers in anesthetized mice that lack the galanin-R1 receptor. Repetitive stimulation of C-fibers induced a gradual increase in Reflex magnitude during the stimulation (wind-up), and a subsequent increase in spinal Reflex excitability (central sensitization). This occurred in GAL-R1 −/− , GAL-R1 +/− , and +/+ wild-type controls, with no significant differences observed between genotypes. Intrathecal administration of galanin markedly blocked the sensitization following the repetitive stimulation in all three groups. No differences between wild-type or galanin-R1 receptor knockout mice were seen. These results confirm previous studies in rats, showing that intrathecal galanin reduces the central sensitization following wind-up. The present data indicate that this effect is probably mediated by receptors other than GAL-R1.
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effects of intrathecal nocistatin on the Flexor Reflex and its interaction with orphanin fq nociceptin
Neuroreport, 1999Co-Authors: Isabella S Xu, Z Wiesenfeldhallin, Maryam Hashemi, Girolamo Calo, Domenico Regoli, Xiao-jun XuAbstract:: We studied the effects of intrathecal (i.t.) nocistatin, a peptide identified from the precursor of orphanin FQ/nociceptin (OFQ) on the spinal nociceptive Flexor Reflex in decerebrate, spinalized, unanesthetized rats and its interaction with i.t. OFQ. Nocistatin induced a moderate, non-dose-dependent facilitation of the Flexor Reflex without producing Reflex depression whereas i.t. OFQ induced a biphasic dose-dependent facilitatory and inhibitory effect. The facilitatory effect of low dose (0.55 pmol) OFQ was significantly increased by nocistatin. On the other hand, the duration, but not magnitude, of Reflex depression induced by a high (550 pmol) dose of OFQ was significantly shortened by 5.5 nmol nocistatin. Thus, nocistatin interacts with OFQ in a complex fashion, increasing excitation and reducing inhibition. No evidence was obtained for an antinociceptive effect of nocistatin in rat spinal cord.
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the effect of intrathecal selective agonists of y1 and y2 neuropeptide y receptors on the Flexor Reflex in normal and axotomized rats
Brain Research, 1999Co-Authors: Isabella S Xu, Xiao-jun Xu, Tomas Hokfelt, Z WiesenfeldhallinAbstract:Abstract We have examined the effects of intrathecal (i.t.) administration of [Leu31,Pro34]-neuropeptide Y (NPY) or NPY-(13–36), selective agonists of NPY Y1 or Y2 receptors, respectively, on the excitability of the Flexor Reflex in normal rats and after unilateral transection of the sciatic nerve. In rats with intact and sectioned sciatic nerves, i.t. [Leu31,Pro34]-NPY induced a similar biphasic effect on the Flexor Reflex with facilitation at low doses and facilitation followed by depression at high doses. In contrast, i.t. NPY-(13–36) only facilitated the Flexor Reflex in normal rats, and at high dose it caused ongoing discharges in the electromyogram. NPY-(13–36) caused dose-dependent depression of the Flexor Reflex in rats after sciatic nerve transection, in addition to its facilitatory effect. Topical application of [Leu31,Pro34]-NPY or NPY-(13–36) caused a moderate and brief reduction in spinal cord blood flow. No difference was noted between the vasoconstrictive effect of [Leu31,Pro34]-NPY and NPY-(13–36). It is suggested that activation of Y1 receptors may be primarily responsible for the Reflex depressive effect of i.t. neuropeptide Y in rats with intact sciatic nerves, whereas both Y1 and Y2 receptors may be involved in mediating the depressive effect of NPY after axotomy.
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effects of intrathecal orphanin fq on a Flexor Reflex in the rat after inflammation or peripheral nerve section
European Journal of Pharmacology, 1999Co-Authors: Isabella S Xu, Z Wiesenfeldhallin, Stefan Grass, Xiao-jun XuAbstract:We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive Flexor Reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092–2094.], intrathecal orphanin FQ induced a dose-dependent depression of the Flexor Reflex with a ED50 of 965 ng. Initial Reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial Reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of Reflex depression was significantly shortened. The ED50 for Reflex depression was 2.4 μg for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED50 for Reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.
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fragments of galanin message associated peptide gmap modulate the spinal Flexor Reflex in rat
European Journal of Pharmacology, 1996Co-Authors: Xiao-jun Xu, Siv Andell, Tamas Bartfai, Z WiesenfeldhallinAbstract:Abstract We have previously reported that galanin message-associated peptide (GMAP), a fragment of galanin precursor protein, is present in dorsal root ganglion cells and upon intrathecal (i.t.) administration influences the spinal nociceptive Flexor Reflex in a complex manner in the rat. GMAP elicited a moderate facilitation of the Flexor Reflex, but when administered prior to conditioning stimulation of C-afferents, it dose dependently blocked spinal cord hyperexcitability. The present study examined the effects of four fragments of GMAP-(1-60), GMAP-(1–12), GMAP-(10–24), GMAP-(25–44) and GMAP-(37–60), on the Flexor Reflex and compared them with the effects of the complete peptide sequence. All four GMAP fragments facilitated the Flexor Reflex. However, this effect was dose-dependent only for GMAP-(1–12) and the effect of GMAP-(1–12) was stronger than GMAP-(1–60). In contrast, only GMAP-(25–44) dose dependently blocked the facilitation of the Flexor Reflex induced by the C-fiber conditioning stimulation. The potency of the blocking effect of GMAP-(25–44) was one order of magnitude lower than that of GMAP-(1–60). The results indicated that two fragments of GMAP are pharmacologically active and produce effects which are similar to the full sequence. It is possible that the complex effect of GMAP may be mediated by different subtypes of GMAP receptors which recognize different portions of the GMAP sequence.
Xiao-jun Xu - One of the best experts on this subject based on the ideXlab platform.
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Flexor Reflex excitability in mice lacking galanin receptor galanin r1
Neuroscience Letters, 2003Co-Authors: Stefan Grass, Xiao-jun Xu, Arie S Jacoby, Tiina P Iismaa, Jacqueline N Crawley, Z WiesenfeldhallinAbstract:Abstract This study was conducted to examine the excitability of the nociceptive Flexor Reflex and its sensitization by repetitive stimulation of C-fibers in anesthetized mice that lack the galanin-R1 receptor. Repetitive stimulation of C-fibers induced a gradual increase in Reflex magnitude during the stimulation (wind-up), and a subsequent increase in spinal Reflex excitability (central sensitization). This occurred in GAL-R1 −/− , GAL-R1 +/− , and +/+ wild-type controls, with no significant differences observed between genotypes. Intrathecal administration of galanin markedly blocked the sensitization following the repetitive stimulation in all three groups. No differences between wild-type or galanin-R1 receptor knockout mice were seen. These results confirm previous studies in rats, showing that intrathecal galanin reduces the central sensitization following wind-up. The present data indicate that this effect is probably mediated by receptors other than GAL-R1.
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effects of intrathecal nocistatin on the Flexor Reflex and its interaction with orphanin fq nociceptin
Neuroreport, 1999Co-Authors: Isabella S Xu, Z Wiesenfeldhallin, Maryam Hashemi, Girolamo Calo, Domenico Regoli, Xiao-jun XuAbstract:: We studied the effects of intrathecal (i.t.) nocistatin, a peptide identified from the precursor of orphanin FQ/nociceptin (OFQ) on the spinal nociceptive Flexor Reflex in decerebrate, spinalized, unanesthetized rats and its interaction with i.t. OFQ. Nocistatin induced a moderate, non-dose-dependent facilitation of the Flexor Reflex without producing Reflex depression whereas i.t. OFQ induced a biphasic dose-dependent facilitatory and inhibitory effect. The facilitatory effect of low dose (0.55 pmol) OFQ was significantly increased by nocistatin. On the other hand, the duration, but not magnitude, of Reflex depression induced by a high (550 pmol) dose of OFQ was significantly shortened by 5.5 nmol nocistatin. Thus, nocistatin interacts with OFQ in a complex fashion, increasing excitation and reducing inhibition. No evidence was obtained for an antinociceptive effect of nocistatin in rat spinal cord.
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the effect of intrathecal selective agonists of y1 and y2 neuropeptide y receptors on the Flexor Reflex in normal and axotomized rats
Brain Research, 1999Co-Authors: Isabella S Xu, Xiao-jun Xu, Tomas Hokfelt, Z WiesenfeldhallinAbstract:Abstract We have examined the effects of intrathecal (i.t.) administration of [Leu31,Pro34]-neuropeptide Y (NPY) or NPY-(13–36), selective agonists of NPY Y1 or Y2 receptors, respectively, on the excitability of the Flexor Reflex in normal rats and after unilateral transection of the sciatic nerve. In rats with intact and sectioned sciatic nerves, i.t. [Leu31,Pro34]-NPY induced a similar biphasic effect on the Flexor Reflex with facilitation at low doses and facilitation followed by depression at high doses. In contrast, i.t. NPY-(13–36) only facilitated the Flexor Reflex in normal rats, and at high dose it caused ongoing discharges in the electromyogram. NPY-(13–36) caused dose-dependent depression of the Flexor Reflex in rats after sciatic nerve transection, in addition to its facilitatory effect. Topical application of [Leu31,Pro34]-NPY or NPY-(13–36) caused a moderate and brief reduction in spinal cord blood flow. No difference was noted between the vasoconstrictive effect of [Leu31,Pro34]-NPY and NPY-(13–36). It is suggested that activation of Y1 receptors may be primarily responsible for the Reflex depressive effect of i.t. neuropeptide Y in rats with intact sciatic nerves, whereas both Y1 and Y2 receptors may be involved in mediating the depressive effect of NPY after axotomy.
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effects of intrathecal orphanin fq on a Flexor Reflex in the rat after inflammation or peripheral nerve section
European Journal of Pharmacology, 1999Co-Authors: Isabella S Xu, Z Wiesenfeldhallin, Stefan Grass, Xiao-jun XuAbstract:We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive Flexor Reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092–2094.], intrathecal orphanin FQ induced a dose-dependent depression of the Flexor Reflex with a ED50 of 965 ng. Initial Reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial Reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of Reflex depression was significantly shortened. The ED50 for Reflex depression was 2.4 μg for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED50 for Reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.
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fragments of galanin message associated peptide gmap modulate the spinal Flexor Reflex in rat
European Journal of Pharmacology, 1996Co-Authors: Xiao-jun Xu, Siv Andell, Tamas Bartfai, Z WiesenfeldhallinAbstract:Abstract We have previously reported that galanin message-associated peptide (GMAP), a fragment of galanin precursor protein, is present in dorsal root ganglion cells and upon intrathecal (i.t.) administration influences the spinal nociceptive Flexor Reflex in a complex manner in the rat. GMAP elicited a moderate facilitation of the Flexor Reflex, but when administered prior to conditioning stimulation of C-afferents, it dose dependently blocked spinal cord hyperexcitability. The present study examined the effects of four fragments of GMAP-(1-60), GMAP-(1–12), GMAP-(10–24), GMAP-(25–44) and GMAP-(37–60), on the Flexor Reflex and compared them with the effects of the complete peptide sequence. All four GMAP fragments facilitated the Flexor Reflex. However, this effect was dose-dependent only for GMAP-(1–12) and the effect of GMAP-(1–12) was stronger than GMAP-(1–60). In contrast, only GMAP-(25–44) dose dependently blocked the facilitation of the Flexor Reflex induced by the C-fiber conditioning stimulation. The potency of the blocking effect of GMAP-(25–44) was one order of magnitude lower than that of GMAP-(1–60). The results indicated that two fragments of GMAP are pharmacologically active and produce effects which are similar to the full sequence. It is possible that the complex effect of GMAP may be mediated by different subtypes of GMAP receptors which recognize different portions of the GMAP sequence.
Brian D Schmit - One of the best experts on this subject based on the ideXlab platform.
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Flexor Reflex decreases during sympathetic stimulation in chronic human spinal cord injury
Experimental Neurology, 2009Co-Authors: Kevin M Garrison, Brian D SchmitAbstract:A better understanding of autonomic influence on motor Reflex pathways in spinal cord injury is important to the clinical management of autonomic dysReflexia and spasticity in spinal cord injured patients. The purpose of this study was to examine the modulation of Flexor Reflex windup during episodes of induced sympathetic activity in chronic human spinal cord injury (SCI). We simultaneously measured peripheral vascular conductance and the windup of the Flexor Reflex in response to conditioning stimuli of electrocutaneous stimulation to the opposite leg and bladder percussion. Flexor Reflexes were quantified using torque measurements of the response to a noxious electrical stimulus applied to the skin of the medial arch of the foot. Both bladder percussion and skin conditioning stimuli produced a reduction (43-67%) in the ankle and hip Flexor torques (p<0.05) of the Flexor Reflex. This reduction was accompanied by a simultaneous reduction in vascular conductance, measured using venous plethysmography, with a time course that matched the Flexor Reflex depression. While there was an overall attenuation of the Flexor Reflex, windup of the Flexor Reflex to repeated stimuli was maintained during periods of increased sympathetic activity. This paradoxical depression of Flexor Reflexes and minimal effect on windup is consistent with inhibition of afferent feedback within the superficial dorsal horn. The results of this study bring attention to the possible interaction of motor and sympathetic Reflexes in SCI above and below the T5 spinal level, and have implications for clinicians in spasticity management and for researchers investigating motor Reflexes post SCI.
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Flexor Reflex decreases during sympathetic stimulation in chronic human spinal cord injury
Experimental Neurology, 2009Co-Authors: M. Kevin Garrison, Brian D SchmitAbstract:A better understanding of autonomic influence on motor Reflex pathways in spinal cord injury is important to the clinical management of autonomic dysReflexia and spasticity in spinal cord injured patients. The purpose of this study was to examine the modulation of Flexor Reflex windup during episodes of induced sympathetic activity in chronic human spinal cord injury (SCI). We simultaneously measured peripheral vascular conductance and the windup of the Flexor Reflex in response to conditioning stimuli of electrocutaneous stimulation to the opposite leg and bladder percussion. Flexor Reflexes were quantified using torque measurements of the response to a noxious electrical stimulus applied to the skin of the medial arch of the foot. Both bladder percussion and skin conditioning stimuli produced a reduction (43-67%) in the ankle and hip Flexor torques (p
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rebound responses to prolonged Flexor Reflex stimuli in human spinal cord injury
Experimental Brain Research, 2009Co-Authors: Brian D Schmit, George T Hornby, Ming Wu, Jennifer H KahnAbstract:The purpose of this study was to examine the Reflex effects of electrical stimulation applied to the thigh using skin electrodes, targeting the sensory fibers of the rectus femoris and sartorius, in people with spinal cord injury (SCI). Thirteen individuals with SCI were recruited to participate in experiments using prolonged electrical stimuli on the right medial thigh over the regions of the sartorius and rectus femoris muscles. Three stimuli, spaced 20 s apart, were applied at 30 Hz for 1 s at four different intensities (15–60 mA) while subjects rested in a seated position. Isometric joint torques of the hip, knee and ankle, and electromyograms (EMGs) from six muscles of the leg were recorded during the stimulation. Early in the stimulation, a flexion response was observed at the hip and ankle, analogous to a Flexor Reflex; however, this response was usually followed by a “rebound” response consisting of hip extension, knee flexion and ankle plantarflexion, occurring in 10/13 subjects. Stimuli applied in a more lateral (mid thigh) electrode position (i.e. over the rectus femoris) were less effective in producing the response than medial placement, despite vigorous quadriceps activation. This complex Reflex response is consistent with activation of a coordinating spinal circuit that could play a role in motor function. The reversal of the Reflex pattern emphasizes the potential connection between skin/muscle afferents of the thigh, possibly including sartorius muscle afferents and locomotor Reflex centers. This knowledge may be helpful in identifying rehabilitation strategies for enhancing gait training in human SCI.
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Flexor Reflex responses triggered by imposed knee extension in chronic human spinal cord injury
Experimental Brain Research, 2006Co-Authors: Brian D Schmit, George T Hornby, Ming Wu, Jennifer H KahnAbstract:Hypersensitivity of the Flexor Reflex pathways to input from force-sensitive muscle afferents may contribute to the prevalence and severity of muscle spasms in patients with spinal cord injury (SCI). In this study, we triggered Flexor Reflexes with constant velocity knee movements in 15 subjects with SCI. Ramp and hold knee extension perturbations were imposed on one leg while the hip and ankle were held in an isometric position using an instrumented leg brace. Knee, ankle and hip torque responses and electromyograms from six muscles of the leg were recorded following controlled knee extension at four different velocities. Tests were conducted with the hip in both flexed and extended positions. During the movement into knee extension, a velocity-dependent stretch Reflex, represented by a progressively increasing knee flexion torque, was observed. In addition, another type of Reflex that resembled a Flexor Reflex (flexion of the hip and ankle) was also triggered by the imposed knee extension. The magnitude of the ankle dorsiflexion torque responses was significantly correlated to the stretch Reflex torque at the knee in 9 of the 15 subjects. We concluded that stretch Reflexes initiate a muscle contraction that then can contribute to a Flexor Reflex response, possibly through muscle group III/IV afferent pathways. These results suggest that spasticity in SCI consists of a myriad of complex Reflex responses that extend beyond stretch Reflexes.
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the intralimb coordination of the Flexor Reflex response is altered in chronic human spinal cord injury
Neuroscience Letters, 2005Co-Authors: Katherine M Deutsch, Brian D Schmit, George T HornbyAbstract:The current study compared the intralimb coordination of Flexor Reflex responses in spinal intact and complete chronic spinal cord injured (SCI) individuals. Noxious electrocutaneous stimulation was applied at the apex of the medial arch of the foot (50 mA, 500 Hz, 1 ms pulse width, 20 ms) in 21 complete chronic SCI and 19 spinal intact volunteers and the Flexor Reflex response was quantified by measuring the isometric joint torques at the ankle, knee and hip. The results showed that SCI individuals had significantly smaller peak knee and hip joint flexion torques, often exhibited a net knee extension torque, and produced a much smaller hip joint flexion torque during the Flexor Reflex response in contrast to the spinal intact individuals. The latency of the Reflex response, measured from the tibialis anterior electromyogram, was comparable in both test populations. These findings indicate that the intralimb coordination of the Flexor Reflex response of chronic complete SCI individuals is altered, possibly reflecting a functional reorganization of the flexion pathways of the spinal cord. Published by Elsevier Ireland Ltd.
Z Wiesenfeldhallin - One of the best experts on this subject based on the ideXlab platform.
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the effect of intrathecal endomorphin 2 on the Flexor Reflex in normal inflamed and axotomized rats reduced effect in rats with autotomy
Neuroscience, 2000Co-Authors: Stefan Grass, Z Wiesenfeldhallin, X J XuAbstract:Abstract Endomorphin-2, a newly discovered endogenous opioid peptide and agonist at the μ-opioid receptor, was injected intrathecally in normal rats and animals with unilateral peripheral inflammation or sciatic nerve section and its effect on the nociceptive Flexor Reflex was analysed. In normal rats, intrathecal endomorphin-2 induced a strong and dose-dependent depression of the Reflex, which was naloxone-reversible. The effect of intrathecal endomorphin-2 was fairly brief, lasting for about 20–30 min at the highest dose, 4 μg. The effect of endomorphin-2 in inflamed rats was not significantly different from that in normals. After nerve section some rats developed autotomy behavior. In these rats endomorphin-2 had significantly reduced effect. However, the Reflex depressive effect of intrathecal endomorphin-2 was unchanged in axotomized rats without autotomy. It is suggested that intrathecal endomorphin-2 has antinociceptive effect in the rat spinal cord under normal and inflammatory conditions. After peripheral nerve injury the sensitivity to endmorphin-2 may be reduced in rats that exhibit ongoing neuropathic pain-like behaviors.
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the effect of intrathecal neuropeptide y on the Flexor Reflex in rats after carrageenan induced inflammation
Neuropeptides, 1998Co-Authors: Isabella S Xu, X J Xu, Tomas Hokfelt, Rurong Ji, Z WiesenfeldhallinAbstract:We examined the effects of intrathecal (i.t.) administration of neuropeptide Y (NPY) on the excitability of the Flexor Reflex in normal rats and 24 h after inflammation induced by subcutaneous carrageenan. In normal rats, i.t. NPY at low doses (10 and 100 ng) caused a brief facilitation of the Flexor Reflex with no subsequent depression. At higher doses (1 and 10 μg), the effect of NPY was mainly inhibitory, causing substantial and usually prolonged depression of the Flexor Reflex. At 24 h after the injection of carrageenan, when inflammation was at its peak, the magnitude of the Reflex was increased and discharge duration became prolonged. I.t. NPY produced similar pattern of dose-dependent facilitatory and depressive effects on the Flexor Reflex. The facilitatory effect of i.t. NPY, particularly for the higher doses, was significantly enhanced in inflamed rats compared to normals. In contrast, the depressive effect of high doses of i.t. NPY was unchanged. These data suggest that the changes in levels of NPY and NPY receptors in the spinal cord known to occur after inflammation, are associated with an increased excitatory effect of this peptide.
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on the role of galanin in mediating spinal Flexor Reflex excitability in inflammation
Neuroscience, 1998Co-Authors: Isabella S Xu, X J Xu, Stefan Grass, Z WiesenfeldhallinAbstract:Abstract The effects of exogenous and endogenous galanin on spinal Flexor Reflex excitability was evaluated in rats one to eight days after the induction of inflammation by subcutaneous injection of carrageenan into the sural nerve innervation area. In normal rats, electrical stimulation of C-fibres in the sural nerve elicited a brisk Reflex discharge. Conditioning stimulation of C-fibres (1/s) generated a gradual increase in Reflex magnitude (wind-up), which was followed by a period of Reflex hyperexcitability. Intrathecal galanin dose-dependently blocked Reflex hyperexcitability induced by C-fibre conditioning stimulation whereas i.t. M-35, a high-affinity galanin receptor antagonist, moderately potentiated this effect. At one to three days after the injection of carrageenen, when inflammation was at its peak, the magnitude of the Reflex was significantly increased and discharge duration became prolonged. However, wind-up and Reflex hyperexcitability were significantly reduced. Furthermore, reduced Reflex excitability during conditioning stimulation (“wind-down”) and depression of the Reflex were sometimes present, which are rarely observed in normal rats. Intrathecal galanin reduced hyperexcitability during inflammation, although its potency was weaker than in normals. However, the galanin receptor antagonist M-35 strongly enhanced wind-up and Reflex hyperexcitability, similarly as in normal rats. The baseline Flexor Reflex, wind-up and C-fibre conditioning stimulation-induced facilitation were normalized four to eight days after carrageenan injection when signs of inflammation were diminishing. Interestingly, intrathecal galanin and M-35 failed to influence spinal excitability. The results suggest a complex functional plasticity in the role of endogenous galanin in mediating spinal excitability during inflammation. There appears to be an enhanced endogenous inhibitory control by galanin on C-afferent input during the peak of inflammation, which may explain the relative ineffectiveness of exogenous galanin. During the recovery phase there may be a reduction in galanin receptors, which may impair the action of endogenous and exogenous galanin. These results further support the notion that galanin is an endogenous inhibitory peptide in nociception.
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intrathecal pituitary adenylate cyclase activating polypeptide facilitates the spinal nociceptive Flexor Reflex in the rat
Neuroscience, 1996Co-Authors: X J Xu, Z WiesenfeldhallinAbstract:Abstract We have examined the effects of intrathecal (i.t.) pituitary adenylate cyclase activating polypeptide on the spinal nociceptive Flexor Reflex in decerebrate, spinalized, unanaesthetized rats. The Flexor Reflex was elicited by electrical stimulation applied subcutaneously to the sural nerve innervation area and recorded as electromyogram activity from ipsilateral hamstring muscles. Pituitary adenylate cyclase activating polypeptide(1–27) was administered over a wide dose range (10 ng to 10 μg) and elicited a dose-dependent facilitation of the Flexor Reflex and did not depress the Reflex at any dose. Furthermore, pituitary adenylate cyclase activating polypeptide did not inhibit the facilitation of the Flexor Reflex induced by repetitive stimulation of C-fibres. It is concluded that pituitary adenylate cyclase activating polypeptide had an excitatory effect on spinal cord function which may indicate a role for this peptide in nociceptive transmission and modulation. Moreover, in contrast to previous studies, we found no evidence suggesting that pituitary adenylate cyclase activating polypeptide exerts antinociceptive action at spinal level.
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the effects of intrathecal galanin message associated peptide gmap on the Flexor Reflex in rats
Regulatory Peptides, 1995Co-Authors: Xiao-jun Xu, Z Wiesenfeldhallin, Siv Andell, Tamas BartfaiAbstract:We have examined the effects of intrathecal (i.t.) galanin message-associated peptide (GMAP), the C-terminal flanking peptide in the galanin (GAL) precursor protein, which is produced in equimolar quantities with galanin and which is upregulated upon axotomy, on the spinal nociceptive Flexor Reflex in decerebrate, spinalized, unanesthetized rats. I.t. GMAP elicited a moderate facilitation of the Flexor Reflex. No depression of baseline Flexor Reflex was observed with any dose of GMAP. The facilitation of the Flexor Reflex induced by conditioning stimulation (CS) of cutaneous C-afferents was dose-dependently blocked by GMAP. The Reflex facilitatory effect of exogenously applied substance P (SP), one of the endogenous modulators of Reflex hyperexcitability following C-fiber CS, was only blocked by GMAP at a relatively high dose. I.t. GMAP did not antagonize the Reflex facilitatory effect of vasoactive intestinal peptide and did not potentiate the Reflex depressive effect of i.t. morphine or clonidine. Finally, 1 μg i.t. GMAP did not influence spinal cord blood flow whereas 10 μg GMAP induced a transient decrease in spinal cord blood flow in some experiments. The ability of GMAP to block the increase in spinal cord excitability following repetitive C-fiber stimulation may be through a presynaptic action. Although some of the effects of GMAP were similar to galanin, distinct differences were found, particularly in interaction with other excitatory and inhibitory agents. It is possible that GMAP exerts its action in the spinal cord through its own specific receptor. GMAP may act similarly to GAL in some, but not all pharmacological functions. The present results could thus represent another example where different peptides arising from the same peptide precursor produce differential pharmacological actions.
X J Xu - One of the best experts on this subject based on the ideXlab platform.
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the effect of intrathecal endomorphin 2 on the Flexor Reflex in normal inflamed and axotomized rats reduced effect in rats with autotomy
Neuroscience, 2000Co-Authors: Stefan Grass, Z Wiesenfeldhallin, X J XuAbstract:Abstract Endomorphin-2, a newly discovered endogenous opioid peptide and agonist at the μ-opioid receptor, was injected intrathecally in normal rats and animals with unilateral peripheral inflammation or sciatic nerve section and its effect on the nociceptive Flexor Reflex was analysed. In normal rats, intrathecal endomorphin-2 induced a strong and dose-dependent depression of the Reflex, which was naloxone-reversible. The effect of intrathecal endomorphin-2 was fairly brief, lasting for about 20–30 min at the highest dose, 4 μg. The effect of endomorphin-2 in inflamed rats was not significantly different from that in normals. After nerve section some rats developed autotomy behavior. In these rats endomorphin-2 had significantly reduced effect. However, the Reflex depressive effect of intrathecal endomorphin-2 was unchanged in axotomized rats without autotomy. It is suggested that intrathecal endomorphin-2 has antinociceptive effect in the rat spinal cord under normal and inflammatory conditions. After peripheral nerve injury the sensitivity to endmorphin-2 may be reduced in rats that exhibit ongoing neuropathic pain-like behaviors.
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the effect of intrathecal neuropeptide y on the Flexor Reflex in rats after carrageenan induced inflammation
Neuropeptides, 1998Co-Authors: Isabella S Xu, X J Xu, Tomas Hokfelt, Rurong Ji, Z WiesenfeldhallinAbstract:We examined the effects of intrathecal (i.t.) administration of neuropeptide Y (NPY) on the excitability of the Flexor Reflex in normal rats and 24 h after inflammation induced by subcutaneous carrageenan. In normal rats, i.t. NPY at low doses (10 and 100 ng) caused a brief facilitation of the Flexor Reflex with no subsequent depression. At higher doses (1 and 10 μg), the effect of NPY was mainly inhibitory, causing substantial and usually prolonged depression of the Flexor Reflex. At 24 h after the injection of carrageenan, when inflammation was at its peak, the magnitude of the Reflex was increased and discharge duration became prolonged. I.t. NPY produced similar pattern of dose-dependent facilitatory and depressive effects on the Flexor Reflex. The facilitatory effect of i.t. NPY, particularly for the higher doses, was significantly enhanced in inflamed rats compared to normals. In contrast, the depressive effect of high doses of i.t. NPY was unchanged. These data suggest that the changes in levels of NPY and NPY receptors in the spinal cord known to occur after inflammation, are associated with an increased excitatory effect of this peptide.
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on the role of galanin in mediating spinal Flexor Reflex excitability in inflammation
Neuroscience, 1998Co-Authors: Isabella S Xu, X J Xu, Stefan Grass, Z WiesenfeldhallinAbstract:Abstract The effects of exogenous and endogenous galanin on spinal Flexor Reflex excitability was evaluated in rats one to eight days after the induction of inflammation by subcutaneous injection of carrageenan into the sural nerve innervation area. In normal rats, electrical stimulation of C-fibres in the sural nerve elicited a brisk Reflex discharge. Conditioning stimulation of C-fibres (1/s) generated a gradual increase in Reflex magnitude (wind-up), which was followed by a period of Reflex hyperexcitability. Intrathecal galanin dose-dependently blocked Reflex hyperexcitability induced by C-fibre conditioning stimulation whereas i.t. M-35, a high-affinity galanin receptor antagonist, moderately potentiated this effect. At one to three days after the injection of carrageenen, when inflammation was at its peak, the magnitude of the Reflex was significantly increased and discharge duration became prolonged. However, wind-up and Reflex hyperexcitability were significantly reduced. Furthermore, reduced Reflex excitability during conditioning stimulation (“wind-down”) and depression of the Reflex were sometimes present, which are rarely observed in normal rats. Intrathecal galanin reduced hyperexcitability during inflammation, although its potency was weaker than in normals. However, the galanin receptor antagonist M-35 strongly enhanced wind-up and Reflex hyperexcitability, similarly as in normal rats. The baseline Flexor Reflex, wind-up and C-fibre conditioning stimulation-induced facilitation were normalized four to eight days after carrageenan injection when signs of inflammation were diminishing. Interestingly, intrathecal galanin and M-35 failed to influence spinal excitability. The results suggest a complex functional plasticity in the role of endogenous galanin in mediating spinal excitability during inflammation. There appears to be an enhanced endogenous inhibitory control by galanin on C-afferent input during the peak of inflammation, which may explain the relative ineffectiveness of exogenous galanin. During the recovery phase there may be a reduction in galanin receptors, which may impair the action of endogenous and exogenous galanin. These results further support the notion that galanin is an endogenous inhibitory peptide in nociception.
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Spinal NK1 receptors contribute to the increased excitability of the nociceptive Flexor Reflex during persistent peripheral inflammation.
Brain research, 1996Co-Authors: A M Parsons, X J Xu, Zsuzsanna Wiesenfeld-hallin, C N Honda, D Budai, V S SeyboldAbstract:Hyperalgesia is a characteristic of inflammation and is mediated, in part, by an increase in the excitability of spinal neurons. Although substance P does not appear to mediate fast synaptic events that underlie nociception in the spinal cord, it may contribute to the hyperalgesia and increased excitability of spinal neurons during inflammation induced by complete Freund's adjuvant. We examined the role of endogenous substance P in changes in the excitability of spinal neurons during adjuvant-induced, peripheral inflammation by determining the effect of a selective NK1 receptor antagonist (RP67580) on the nociceptive Flexor Reflex in adult rats. Experiments were conducted 2 or 3 days after injection of adjuvant. Animals exhibited moderate thermal hyperalgesia at this time. The Flexor Reflex was evoked by electrical stimulation of the sural nerve and was recorded in the ipsilateral hamstring muscles. The Flexor Reflex ipsilateral to the inflamed hindpaw was enhanced approximately two-fold compared to the Flexor Reflex evoked in untreated animals as determined by the number of potentials and the duration of the Reflex. The enhanced Reflex in adjuvant-treated animals was most likely due to an increase in the excitability of spinal interneurons because short-latency activity in the hamstring muscles did not differ between untreated animals and adjuvant-treated animals following electrical stimulation of the L5 dorsal root or the nerve innervating the muscle with a stimulus that was 1.3-1.5 times the threshold for excitation of A-fibers. Intrathecal administration of RP67580 (2.3 and 6.8 nmol) attenuated the Flexor Reflex evoked in adjuvant-treated animals, but had no effect in untreated animals. Intravenous or intraplantar injection of RP67580 (6.8 nmol) did not affect the Flexor Reflex in adjuvant-treated animals indicating a spinal action of the drug following intrathecal administration. RP68651, the enantiomer of RP67580, was without effect at doses up to 6.8 nmol, indicating that the effects of comparable doses of RP67580 were due to an action of the drug at NK1 receptors. However, intrathecal administration of 23 nmol of both drugs attenuated the Reflex in adjuvant-treated and control animals indicating that effects of RP67580 at this dose were not mediated entirely by its action at NK1 receptors. Overall, these data suggest that endogenous substance P has a role in the increased excitability of spinal interneurons observed during persistent inflammation and support the hypothesis that substance P released in the spinal cord contributes to the hyperalgesia that accompanies adjuvant-induced persistent, peripheral inflammation.
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intrathecal pituitary adenylate cyclase activating polypeptide facilitates the spinal nociceptive Flexor Reflex in the rat
Neuroscience, 1996Co-Authors: X J Xu, Z WiesenfeldhallinAbstract:Abstract We have examined the effects of intrathecal (i.t.) pituitary adenylate cyclase activating polypeptide on the spinal nociceptive Flexor Reflex in decerebrate, spinalized, unanaesthetized rats. The Flexor Reflex was elicited by electrical stimulation applied subcutaneously to the sural nerve innervation area and recorded as electromyogram activity from ipsilateral hamstring muscles. Pituitary adenylate cyclase activating polypeptide(1–27) was administered over a wide dose range (10 ng to 10 μg) and elicited a dose-dependent facilitation of the Flexor Reflex and did not depress the Reflex at any dose. Furthermore, pituitary adenylate cyclase activating polypeptide did not inhibit the facilitation of the Flexor Reflex induced by repetitive stimulation of C-fibres. It is concluded that pituitary adenylate cyclase activating polypeptide had an excitatory effect on spinal cord function which may indicate a role for this peptide in nociceptive transmission and modulation. Moreover, in contrast to previous studies, we found no evidence suggesting that pituitary adenylate cyclase activating polypeptide exerts antinociceptive action at spinal level.