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Mu and delta opioid receptors on nociceptors attenuate mechanical hyperalgesia in rat.
Joseph EK, Levine JD (2010) Mu and delta opioid receptors on nociceptors attenuate mechanical hyperalgesia in rat. Neuroscience 171(1):344-350. doi: 10.1016/j.neuroscience.2010.08.035
Summary: In this work the authors analyzed nociceptor populations mediating mechanical hyperalgesia in the rat. Rats received 3.2 µg of IB4-SAP (Cat. #IT-10) into the subarachnoid space between the L4 and L5 vertebrae. Hyperalgesia due to the administration of NGF was inhibited by DAMGO and SNC even in lesioned animals. These data indicate that most nociceptor populations are involved in mechanical hyperalgesia, and that the mu opioid and delta opioid receptors are co-expressed on some TrkA-positive nociceptors.
Related Products: IB4-SAP (Cat. #IT-10)
Hyperalgesic priming is restricted to isolectin B4-positive nociceptors.
Joseph EK, Levine JD (2010) Hyperalgesic priming is restricted to isolectin B4-positive nociceptors. Neuroscience 169(1):431-435. doi: 10.1016/j.neuroscience.2010.04.082
Summary: Hyperalgesic priming is an injury that induces a chronic pain state marked by the presence of inflammatory cytokines. The authors evaluated which populations of nociceptors are involved in the priming process. Rats that received 3.2 µg intrathecal injections of IB4-SAP (Cat. #IT-10) failed to establish priming. Acute mechanical hyperalgesia could still be induced, indicating that IB4+ nociceptors are necessary for priming, but a different nociceptor group is involved with nociceptor sensitization.
Related Products: IB4-SAP (Cat. #IT-10)
Enrichment of xenograft-competent genetically modified pig cells using a targeted toxin, isolectin BS-I-B4 conjugate.
Akasaka E, Watanabe S, Himaki T, Ohtsuka M, Yoshida M, Miyoshi K, Sato M (2010) Enrichment of xenograft-competent genetically modified pig cells using a targeted toxin, isolectin BS-I-B4 conjugate. Xenotransplantation 17:81-89. doi: 10.1111/j.1399-3089.2010.00568.x
Summary: Genetically modified pigs lacking the gala1-3gal epitope may be suitable for production of organs that could be transplanted to humans. The ability to select for a homozygous population of donor somatic cells would accelerate the process of generating these animals, which would otherwise take approximately 2 years. The authors incubated a heterozygous population of 107 porcine embryonic fibroblasts with 1.6 µg of IB4-SAP (Cat. #IT-10). Even after 6 months the treated cells were negative for the agal epitope.
Related Products: IB4-SAP (Cat. #IT-10)
Dependence of monocyte chemoattractant protein 1 induced hyperalgesia on the isolectin B4-binding protein versican.
Bogen O, Dina OA, Gear RW, Levine JD (2009) Dependence of monocyte chemoattractant protein 1 induced hyperalgesia on the isolectin B4-binding protein versican. Neuroscience 159:780-786. doi: 10.1016/j.neuroscience.2008.12.049
Summary: Monocyte chemoattractant protein 1 (MCP-1) is involved in generation of inflammatory and neuropathic pain, but the mechanisms underlying this involvement are not understood. Rats received 3.2 µg intrathecal injections of IB4-SAP (Cat. #IT-10). Ten days later the rats received intradermal MCP-1. Animals treated with IB4-SAP did not exhibit the mechanical hyperalgesia normally seen when treated with MCP-1.
Related Products: IB4-SAP (Cat. #IT-10)
GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versican.
Bogen O, Joseph EK, Chen X, Levine JD (2008) GDNF hyperalgesia is mediated by PLCgamma, MAPK/ERK, PI3K, CDK5 and Src family kinase signaling and dependent on the IB4-binding protein versican. Eur J Neurosci 28:12-19. doi: 10.1111/j.1460-9568.2008.06308.x
Summary: C-fiber nociceptors have been divided into NGF and GDNF classes. Here the authors examined the function of an isolectin B4-binding subpopulation of these nocicepetors. Rats received 40 ng of IB4-SAP (Cat. #IT-10) into the intrathecal space between the fifth and sixth lumbar vertebrae. The results demonstrate that GDNF sensitizes IB4+ C-fiber nociceptors and causes mechanical hyperalgesia.
Related Products: IB4-SAP (Cat. #IT-10)
IB4 afferent sprouting contributes to bladder dysfunction in spinal rats.
Zinck ND, Downie JW (2008) IB4 afferent sprouting contributes to bladder dysfunction in spinal rats. Exp Neurol 213:293-302. doi: 10.1016/j.expneurol.2008.06.006
Summary: Spinal cord injury can cause inefficient bladder function, but the direct cause is not well understood. Most work has focused on afferent neurons that contain CGRP and respond to NGF. Here the authors investigate the role of isolectin B4 (IB4)-expressing neurons that are supported by GDNF. Rats received intrathecal injections of either 2.4 µg IB4-SAP (Cat. #IT-10) or 3 µg control saporin (Cat. #PR-01). The data suggest that IB4-afferent sprouting is involved in bladder dysfunction following spinal cord transection.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy.
Joseph EK, Chen X, Bogen O, Levine JD (2008) Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. J Pain 9:463-472. doi: 10.1016/j.jpain.2008.01.335
Summary: Oxaliplatin is a platinum-based chemotherapy agent. Use of this reagent produces various pathological pain states, depending on the dosage site. The authors administered 3.2-µg intrathecal injections of IB4-SAP (Cat. #IT-10), using saporin (Cat. #PR-01) as a control. Lesioning IB4-binding neurons in the dorsal horn completely prevented oxaliplatin-induced hyperalgesia, indicating that the IB4-positive nociceptor neuronal subset is crucial to this type of neuropathy.
Related Products: Saporin (Cat. #PR-01), IB4-SAP (Cat. #IT-10)
Changes in neurokinin-1 receptor expression in populations of spinal lamina I neurons in rats lacking non-peptidergic nociceptive fibers
Saeed AW, Ribeiro-Da-Silva A (2007) Changes in neurokinin-1 receptor expression in populations of spinal lamina I neurons in rats lacking non-peptidergic nociceptive fibers. Neuroscience 2007 Abstracts 821.4/FF19. Society for Neuroscience, San Diego, CA.
Summary: Neurokinin-1 receptor (NK-1r)-containing lamina I projection neurons are deeply involved in the transmission of pain-related information to the brain. Previous studies have shown that lamina I neurons can be classified morphologically into fusiform, pyramidal and multipolar cells, and that these types differ in functional properties, with the pyramidal type being non-nociceptive. Our laboratory has shown not only a considerable increase in immunoreactivity for the NK-1r in animals with CFA-induced arthritis but also a de novo expression of these receptors by pyramidal neurons (Almarestani et al., Soc.Neurosci.Abstr., Program # 249.11, 2006). Based on this, we deemed it interesting to study whether pyramidal neurons would also express NK-1r in an animal model in which we have previously shown a drastic increase in NK-1r expression but no augmented nociceptive responses. To achieve this, we injected, under anesthesia, saporin (SAP) conjugated to the lectin IB4 into the left sciatic nerve of male Sprague Dawley rats to selectively lesion the non-peptidergic nociceptive C-fibers. Animals were sacrificed from 2 weeks to 2 months post-lesion. Horizontal sections of spinal segments L5 and L6 were cut and processed for IB4 binding and NK-1r immunoreactivity using immunofluorescence. Examination of IB4-SAP treated rats at several time points post-lesion revealed increased expression of NK-1r by lamina I cells of the fusiform and multipolar types on the side ipsilateral to the lesion, compared to the contralateral side and to controls. However, pyramidal cells seldom expressed the NK-1r in both control and lesioned animals. Surprisingly, we also observed a direct innervation of lamina I neurons by IB4-positive neurons in control animals, which did not occur ipsilaterally in lesioned animals. These observations support the concept that increased activity by the peptidergic nociceptive afferents may be important in the maintenance of nociceptive responses in the absence of non-peptidergic fibers.
Related Products: IB4-SAP (Cat. #IT-10)
Selective ablation of non-peptidergic C-fibers using IB4-saporin as a tool to identify the functional role of these fibers in pain transmission
Bailey AL, Bennett G, Ribeiro-da-Silva A (2005) Selective ablation of non-peptidergic C-fibers using IB4-saporin as a tool to identify the functional role of these fibers in pain transmission. Neuroscience 2005 Abstracts 169.14. Society for Neuroscience, Washington, DC.
Summary: Non-peptidergic primary sensory afferents represent a sub-population of unmyelinated C-fibres implicated in the transmission of pain-related information. Evidence indicates that these afferents play a role in pain transmission distinct from peptidergic afferents. However, their exact function in pain signalling is unknown. Investigating alterations in pain behaviours and changes in neurotransmitter and receptor expression in the absence of these sensory afferents may provide some insight into their relative importance in acute and chronic pain conditions. We therefore examined the functional consequences of the selective ablation of non-peptidergic fibres in numerous models of acute pain using Isolectin B4 conjugated to saporin (IB4-SAP). Unilateral injection of IB4-SAP into the sciatic nerve resulted in the selective ablation of IB4-positive neurons in the ipsilateral dorsal root ganglion (DRG). Examination of the central terminals of non-peptidergic primary afferents in the dorsal horn revealed the near complete loss of IB4-positive, P2X3 immunoreactive (IR) varicosities. Moreover, there were marked decreases in TRPV1-IR and substance P (SP-IR) with no change in calcitonin-gene-related peptide (CGRP). Examination of a marker of inhibitory interneurons revealed no changes in GAD-IR. Behavioural analysis showed that IB4-SAP treatment had no effect on acute thermal sensitivity, acute mechanical or cold sensitivity. In an animal model of acute inflammation, IB4-SAP treatment had no effect on inflammatory heat hyperalgesia or mechanical allodynia. However, animals treated with IB4-SAP showed attenuated heat hyperalgesia induced by capsaicin 30 and 60 minutes post-injection. Data relative to acute nociceptive thresholds after other chemical stimuli will be presented. These data indicate that non-peptidergic fibres are minimally involved in acute and inflammatory pain, and may play a more prominent role in high threshold thermal sensation.
Related Products: IB4-SAP (Cat. #IT-10)
Role of IB4-containing afferents in the effect of IT clonidine
Li X, Bynum T, Hayashida K, Eisenach JC (2005) Role of IB4-containing afferents in the effect of IT clonidine. Neuroscience 2005 Abstracts 171.22. Society for Neuroscience, Washington, DC.
Summary: Alpha2 adrenoceptors diminish pain transmission in animals with normal condition. Our previous data demonstrated clonidine, an Alpha2 adrenoceptor agonist, inhibited calcium influx after an electrical stimulation in the acutely cultured DRG cells from normal animal, 80% of which are Isolectin B4 (IB4) positive. Therefore we assume intrathecal clonidine produces antinociception primarily by actions on IB4-expressing afferents, and clonidine effect will be decreased with the loss of IB4 containing afferents. In the current report, normal rats received an intra-nerve injection of 2 μg of saporin conjugated IB4 (Sap-IB4), a targeted cytotoxin to IB4-expressing neurons, or a 6 μg of saporin as the control in the rat sciatic nerve. Effects of 30 μg intrathecal clonidine were observed for antinociception to thermal and mechanical stimuli in both ipsi- and contra- lateral side to the injection weekly, before and after Sap-IB4 injection for three weeks. Immunocitochemistry study demonstrated that three weeks of Sap-IB4 treatment dramatically decreased IB4 expression in DRG cells or spinal afferent fibers in the ipslateral side. The basal thermal withdrawal latency and mechanical withdrawal threshold were slightly increased by Sap-IB4 in the ipsilateral side one week after injection, which were returned to normal three weeks later. Additionally, the effeccy of 30 μg clonidine for antinociception to thermal and mechanical stimuli was significantly decreased at the end of treatment. These observations suggested IB4 containing afferents may play a very important role in intrathecal clonidine mediated antinociception.
Related Products: IB4-SAP (Cat. #IT-10)