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Intrathecal substance p-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation.
Wiese AJ, Rathbun M, Butt MT, Malkmus SA, Richter PJ, Osborn KG, Xu Q, Veesart SL, Steinauer JJ, Higgins D, Lappi DA, Russell B, Yaksh TL (2013) Intrathecal substance p-saporin in the dog: distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology 119(5):1163-1177. doi: 10.1097/ALN.0b013e3182a95164
Summary: Here the authors investigate the safety parameters of SP-SAP on purpose-bred beagles (currently in human clinical trials). The dogs received 1.5, 15, or 150 μg intrathecal injections of the conjugate. SP-SAP pharmacology and physiological effects were assessed by behavioral and functional observations, immunohistochemistry, ELISA, blood and urine analysis, histopathology, and in situ hybridization. The general conclusions include that neurokinin-1 receptor (NK1r) positive neuron loss is detectable as soon as 7 days after administration of SP-SAP, the neuron loss is permanent, toxicity is specific to NK1r-positive neurons, and, other than the 150 μg dose, NK1r neuron loss was restricted to the superficial dorsal horn.
Related Products: SP-SAP (Cat. #IT-07), SP-SAP (Cat. #IT-07)
Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain.
Brown DC, Agnello K (2013) Intrathecal substance p-saporin in the dog: efficacy in bone cancer pain. Anesthesiology 119(5):1178-1185. doi: 10.1097/ALN.0b013e3182a95188
Summary: This work demonstrates the use of naturally occurring bone cancer in dogs as a model for pain therapy. Companion dogs with bone cancer received 20-60 μg intrathecal injections of SP-SAP (currently in human clinical trials) depending on the size of the dog. Significantly more dogs in the control group required unblinding and adjustment of pain care than in the SP-SAP group, indicating the efficacy of SP-SAP in pain control. This study also demonstrates the validity of the dog model for testing analgesic protocols.
Related Products: SP-SAP (Cat. #IT-07)
Substance P-saporin for bone cancer pain in dogs: Can man’s best friend solve the lost in translation problem in analgesic development?
Hayashida K (2013) Substance P-saporin for bone cancer pain in dogs: Can man’s best friend solve the lost in translation problem in analgesic development?. Anesthesiology 119(5):999-1000. doi: 10.1097/ALN.0b013e3182a951a2
Summary: This editorial describes the SP-SAP papers in this latest issue of Anesthesiology. The results of the paper are discussed, and the potential in using companion dogs for pain models is emphasized. While most pain models have been rodent-based, companion dogs provide models for chronic pain due to natural causes such as cancer and arthritis, along with frequent opportunity for behavioral assessments by the owner. Such assessments can be done without stress to the animal.
Related Products: SP-SAP (Cat. #IT-07)
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Lamina I NK1 expressing projection neurones are functional in early postnatal rats and contribute to the setting up of adult mechanical sensory thresholds.
Man SH, Geranton SM, Hunt SP (2012) Lamina I NK1 expressing projection neurones are functional in early postnatal rats and contribute to the setting up of adult mechanical sensory thresholds. Mol Pain 8(1):35. doi: 10.1186/1744-8069-8-35
Summary: Projections from lamina I neurons regulate mechanical and thermal sensitivity due to injury. Little is known about how these pathways develop immediately after birth. Rats at postnatal day 3 were treated with 2 μl of 5 μM SP-SAP (Cat. #IT-07) injected into the intrathecal space. Blank-SAP (Cat. #IT-21) was used as a control. The data show that neurokinin-1 positive neurons project to the parabrachial nucleus in the hindbrain, and that these neurons and lamina I neurons were responsive to noxious stimulation at postnatal day 3. Treated animals also displayed increased mechanical sensitivity from postnatal day 45 on.
Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)
Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats.
Wilkinson KA, Fu Z, Powell FL (2011) Ventilatory effects of substance P-saporin lesions in the nucleus tractus solitarii of chronically hypoxic rats. Am J Physiol Regul Integr Comp Physiol 301(2):R343-R350. doi: 10.1152/ajpregu.00375.2010
Summary: Interaction of the multiple brainstem areas that have been established as CO2-sensitive is not well understood. In order to investigate chemoreceptor roles in the nucleus tractus solitarii (NTS) the authors injected 2.6 ng of SP-SAP (alternative: SSP-SAP; Cat. #IT-11) into the caudal NTS of rats. Blank-SAP (Cat. #IT-21) was used as a control. The results indicate that neurokinin-1 receptor-expressing cells in the NTS contribute to plasticity during chronic hypoxia.
Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21)
Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia.
de Carvalho D, Bicego KC, de Castro OW, da Silva GS, Garcia-Cairasco N, Gargaglioni LH (2010) Role of neurokinin-1 expressing neurons in the locus coeruleus on ventilatory and cardiovascular responses to hypercapnia. Respir Physiol Neurobiol 172(1-2):24-31. doi: 10.1016/j.resp.2010.04.016
Summary: NK-1 receptors (NK1R) play an important role in cardiorespiratory responses to hypercapnia. In order to paint a clearer picture of the systems involved the authors injected 0.4 µl of 2 µM SP-SAP (Cat. #IT-07) into the locus coeruleus (LC) of rats. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The data suggest that several subpopulations of neurons express NK1R in the LC, and that these subpopulations play different roles in the modulation of cardiorespiratory reponses to hypercapnia.
Related Products: SP-SAP (Cat. #IT-07), Mouse IgG-SAP (Cat. #IT-18)
Synaptic plasticity and pain: role of ionotropic glutamate receptors.
Larsson M, Broman J (2011) Synaptic plasticity and pain: role of ionotropic glutamate receptors. Neuroscientist 17(3):256-73. doi: 10.1177/1073858409349913
Summary: This review discusses the role of glutaminergic sensory synapses in pain hypersensitivity caused by tissue or nerve injury. The focus is on the roles of ionotrophic glutamate receptors, and how they are involved in dorsal horn synaptic plasticity. The role of substance P in such mechanisms is briefly discussed, as elucidated by the use of SP-SAP (Cat. #IT-07).
Related Products: SP-SAP (Cat. #IT-07)
Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats.
Carstens EE, Carstens MI, Simons CT, Jinks SL (2010) Dorsal horn neurons expressing NK-1 receptors mediate scratching in rats. Neuroreport 21:303-308. doi: 10.1097/WNR.0b013e328337310a
Summary: The itch signal is passed through the superficial dorsal horn. The authors investigated whether ablation of NK-1 receptor-expressing neurons in this area would affect itch-related scratching behavior. Rats received 20 µl of 2.27-µM SP-SAP (Cat. #IT-07) as an intracisternal injection. The reduction in itch response to intradermal 5-hydroxytryptamine indicates that NK-1 receptor-expressing superficial dorsal horn neurons are important for spinal itch transmission.
Related Products: SP-SAP (Cat. #IT-07)
Substance P neurotransmission and violent aggression: the role of tachykinin NK(1) receptors in the hypothalamic attack area.
Halasz J, Zelena D, Toth M, Tulogdi A, Mikics E, Haller J (2009) Substance P neurotransmission and violent aggression: the role of tachykinin NK(1) receptors in the hypothalamic attack area. Eur J Pharmacol 611:35-43. doi: 10.1016/j.ejphar.2009.03.050
Summary: Stimulation of the hypothalamic attack area elicits biting attacks in rats. The authors eliminated NK1 receptor-expressing neurons in this area with bilateral 6.25-ng injections of SP-SAP (Cat. #IT-07). Violent attacks were dramatically reduced while milder forms of aggression remained unchanged, indicating that these two forms of aggression are controlled via different pathways. Lesioned animals also displayed reduced anxiety-like behavior in the elevated plus-maze, suggesting a connection between the hypothalamic attack area and brain areas controlling anxiety.
Related Products: SP-SAP (Cat. #IT-07)
Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain.
Rivat C, Vera-Portocarrero LP, Ibrahim MM, Mata HP, Stagg NJ, De Felice M, Porreca F, Malan TP (2009) Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain. Eur J Neurosci 29:727-737. doi: 10.1111/j.1460-9568.2009.06616.x
Summary: Opioids activate hyperalgesia and allodynia. The authors test the hypothesis that NK-1 receptor-containing ascending pathways play a role in sensitivity to fentanyl. Rats received an intrathecal injection of SP-SAP (Cat. #IT-07), and controls received saporin (Cat. #PR-01). The data indicate that these ascending pathways have a role in fentanyl-induced hyperalgesia.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)