Kras J, Weisshaar C, Pall P, Winkelstein B (2015) Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents. Neurosci Lett 604:193-198. doi: 10.1016/j.neulet.2015.07.043

Summary: Both peptidergic and non-peptidergic neurons innervate the facet joint, which is the source of pain in a majority of neck trauma. In this work the authors examined these subpopulations of neurons to determine the contribution of each in facet joint pain. 100 ng of SSP-SAP (Cat. #IT-11) was injected into bilateral C6/C7 facet joints of rats. Alternatively, rats received 5 μg of rIB4-SAP (Cat. #IT-10) via the same method. Saporin (Cat. #PR-01) was used as control. SSP-SAP, but not rIB4-SAP was able to prevent NGF-induced mechanical and thermal hypersensitivity. SSP-SAP administration also prevented behavioral hypersensitivity and NGF upregulation in the dorsal root ganglion after facet joint distraction. The data indicate that interference with peptidergic signaling within the facet joint may be a treatment for pain originating in that location.

Related Products: SSP-SAP (Cat. #IT-11), IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Araldi D, Ferrari L, Levine J (2015) Repeated mu-opioid exposure induces a novel form of the hyperalgesic priming model for transition to chronic pain. J Neurosci 35:12502-12517. doi: 10.1523/JNEUROSCI.1673-15.2015

Summary: Repeated administration of mu-opioid receptor agonists can lead to persistent mechanical hyperalgesia. One current hypothesis is that a form of hyperalgesic priming is triggered by the repeated activation of these receptors. Classic hyperalgesic priming is associated with signaling via protein kinase Cε (PKε), which is mediated by isolectin-B4+ (IB4) nociceptors. In this work the authors eliminated the IB4+ nociceptors with a 3.2 μg intrathecal injection of recombinant IB4-SAP (Cat. #IT-10). The authors found that hyperalgesic priming induced through the use of DAMGO was dependent on protein kinase A activation rather than activation of PKε. This work demonstrates a novel model for hyperalgesic priming transitioning to chronic pain.

Related Products: IB4-SAP (Cat. #IT-10)

Saeed A, Pawlowski S, Ribeiro-da-Silva A (2015) Limited changes in spinal lamina I dorsal horn neurons following the cytotoxic ablation of non-peptidergic C-fibers. Mol Pain 11:54. doi: 10.1186/s12990-015-0060-z

Summary: For the most part nociceptive information is moved from the periphery to the spinal cord through small diameter primary afferents. One subclass of these afferents is further divided into peptidergic and non-peptidergic populations. The authors examined the role of the non-peptidergic afferents in normal nociception and pain, especially the aspect that in rat neuropathic and inflammatory pain models there is novel expression of neurokinin-1 receptors in some neurons normally devoid of this protein. Rats received 4.8-μg injections of rIB4-SAP (Cat. #IT-10) into the left sciatic nerve, over three injection sites. While the number of non-peptidergic neurons was significantly reduced, de novo expression of the neurokinin-1 receptor was not increased in lamina I pyramidal projection neurons.

Related Products: IB4-SAP (Cat. #IT-10)

Oyamaguchi A, Abe T, Sugiyo S, Niwa H, Takemura M (2016) Selective elimination of isolectin B4-binding trigeminal neurons enhanced formalin-induced nocifensive behavior in the upper lip of rats and c-Fos expression in the trigeminal subnucleus caudalis. Neurosci Res 103:40-47. doi: 10.1016/j.neures.2015.07.007

Summary: In adult rats non-peptidergic neurons and peptidergic neurons innervate different areas and layers of the lamina. It is thought that these two neuronal populations play different roles in nociceptive processing, but the specific function of each group is not well understood. In order to investigate peptidergic and non-peptidergic neurons in orofacial pain processing the authors injected the cisterna magna of rats with 2.9 μg of rIB4-SAP (Cat. #IT-10). Blank-SAP (Cat. #IT-21) was used as a control. The lesioned animals displayed more frequent face-rubbing responses on the administration of formalin, indicating that IB4-binding neurons in the trigeminal nerve play an anti-nociceptive role in response to this type of pain.

Related Products: IB4-SAP (Cat. #IT-10), Blank-SAP (Cat. #IT-21)

Ono K, Ye Y, Viet C, Dang D, Schmidt B (2015) TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity. J Neurophysiol 113:3345-3355. doi: 10.1152/jn.00973.2014

Summary: In order to determine whether IB4-positive trigeminal sensory neurons affect pain sensitivity, the authors administered 2 μg of rIB4-SAP (Cat. #IT-10) to the right infraorbital foramen. Saporin (Cat. #PR-01) was used as a control.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Sato M, Watanabe S (2015) Featured Article: Drug-free selection of stable transfectants using targeted toxin technology and a vector expressing cell-surface carbohydrate-digesting enzyme. Targeting Trends 16(2)

Related Products: IB4-SAP (Cat. #IT-10)

Read the featured article in Targeting Trends.

See Also:

• Sato M et al. A combination of targeted toxin technology and the piggyBac-mediated gene transfer system enables efficient isolation of stable transfectants in nonhuman mammalian cells. Biotechnol J 10:143-153, 2015.

Devesa I, Ferrándiz-Huertas C, Mathivanan S, Wolf C, Luján R, Changeux J, Ferrer-Montiel A (2014) αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors. Proc Natl Acad Sci U S A 111:18345-18350. doi: 10.1073/pnas.1420252111

Summary: The sensitization of transient receptor potential vanilloid 1 (TRPV1) can lead to the development and maintenance of chronic pathological pain conditions. In this work the authors determined that TRPV1 receptors use membrane insertion mechanisms in order to potentiate neuronal excitability. In order to specifically link this activity to peptidergic neurons the authors treated rat primary dorsal root ganglion cultures with 10 mM rIB4-SAP (Cat. #IT-10) to deplete the non-peptidergic neurons.

Related Products: IB4-SAP (Cat. #IT-10)

Sato M, Inada E, Saitoh I, Matsumoto Y, Ohtsuka M, Miura H, Nakamura S, Sakurai T, Watanabe S (2015) A combination of targeted toxin technology and the piggyBac-mediated gene transfer system enables efficient isolation of stable transfectants in nonhuman mammalian cells. Biotechnol J 10:143-153. doi: 10.1002/biot.201400283

Summary: In this work the authors developed a new transfection strategy that takes advantage of the fact that many cell lines endogenously express α-1,3-galactosyltransferase (α-Gal), the target of rIB4-SAP (Cat. #IT-10). After transfection low expressing or non-transfected cells are killed by an application of rIB4-SAP at 80 μg/ml for 2 hours. The surviving cells eventually express α-Gal again, and require no selective agent to maintain expression of the gene of interest. These transfected cells can be transfected again using the same method.

Related Products: IB4-SAP (Cat. #IT-10)

Read the featured article in Targeting Trends.

Kohls MD, Lappi DA, Ancheta LR (2014) Properties of recombinant isolectin B4 (IB4): Binding and immunostaining. Neuroscience 2014 Abstracts 627.07. Society for Neuroscience, Washington, DC.

Summary: Isolectin B4 (IB4) is a protein found in the seeds of Griffonia simplicifolia, a woody climbing shrub native to western and central Africa. Although initially used as an identifier and agglutination agent for B-type red blood cells, it has since become widely used in the neurosciences as a neuronal tracer, for labeling specific populations in the spinal cord, and as a targeting moiety for delivering toxins to specific cells. Recent developments in response to competition from the nutritional supplement industry have reduced the available supply of seeds from which the native protein is purified. In order to create a consistent supply of pure and active IB4 we have determined the full nucleotide sequence of the IB4 gene, cloned it from Griffonia genomic DNA, and expressed recombinant IB4 in E. coli. The recombinant IB4 (rIB4) was purified and tested in several activity assays against the native protein. A fusion protein of rIB4 and GFP was created to demonstrate the use of this protein in immunostaining. Griffonia also contains isolectin A that agglutinates A-type red blood cells – the A and B lectins form tetramers with varying subunit combinations. These tetramers are potential sources of contamination in preparations of the native protein. rIB4 is completely free of any A lectin contamination. The rIB4 is highly pure, and has identical activity to the native protein.

Related Products: IB4-SAP (Cat. #IT-10)

Alvarez P, Green P, Levine J (2014) Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat. Pain 155:1161-1167. doi: 10.1016/j.pain.2014.03.004

Summary: In order to better understand where monocyte chemoattractant protein 1 (MCP-1) fits in the chronic pain landscape the authors performed a series of experiments using antisense and mismatch oligodeoxynucleotides against the MCP-1 receptor in rats. Some animals also received 3.2 μg intrathecal injections of IB4-SAP (Cat. #IT-10). IB4-SAP treatment removed water avoidance stress-induced muscle hyperalgesia, as well as preventing stress-induced hyperalgesic priming that is a usual response to administration of MCP-1. The data indicate that MCP-1 takes action through its receptors on IB4+ nociceptors.

Related Products: IB4-SAP (Cat. #IT-10)